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Russell 2000, bitcoin usd, cmc crypto 200, the most-read case studies of 2021, and the profs who wrote them.

Debapratim Pukayastha of ICFAI Business School in India topped the Case Centre’s list of the world’s top case studies for the sixth straight year. Sadly, Pukayastha passed away in May from Covid-19.

Harvard Business School, which invented both the first MBA program and the business case method, remains king of the case study 100 years later, according to the latest international ranking of case authors.

The Case Centre, a nonprofit that distributes the largest collection of management case studies to business schools across the world, today (October 25) unveiled its 2020-21 Top 50 Bestselling Case Authors. HBS had more case authors (nine) on the list than any other business school. However, ICFAI Business School in India was close behind with seven authors, including all three top individual spots. INSEAD had four authors in the top 10, while Harvard has two top-10 authors.

Case studies, which use real-life problems faced by business executives, are still one of the most widely used education tools for MBA students across the globe. More than 8,800 faculty are registered as authors with The Case Centre. This year’s list of best-selling cases includes each author’s top-selling cases — and though MBA students may not recognize the names of a case study’s author, the titles are more likely ring a bell.

SIX YEARS AT NO. 1, BUT A POSTHUMOUS HONOR

Debapratim Pukayastha of ICFAI Business School (IBS) in India topped the Case Centre’s list of bestselling authors for the sixth straight year. He has earned the distinction every year since the Case Centre began issuing yearly awards for case writing. But this year’s award was a bittersweet honor, as Pukayastha passed away in May from Covid-19.

“Selling over 100,000 copies from an extensive back catalogue of cases since the list was introduced in 2016, Debapratim’s undoubted impact on the case method and management education will live on for years through the many case authors and teachers he has inspired,” the Case Centre announced, “and the vast number of students whose education has been enhanced by learning through his cases.”

Among Pukayastha’s best-selling cases are an examination of safety lapses at a BP oil refinery in Texas City that led to one of the most serious workplace accidents in U.S. history; a case looking at Netflix’s leveraging of Big Data to predict hits; and a case examining how Procter & Gamble develops new products. Besides his annual plaudits for bestselling case, he also won the Case Centre’s Outstanding Contribution to the Case Method Award in 2015, 2018, and 2019.

“I believe that one can be a good teacher without being a good case writer, but it’s not possible to be a good case writer without being a good teacher,” Pukayastha wrote in an author profile on the Case Centre website . “However, I have also found that regularly writing cases can greatly improve classroom teaching. Case writing can be a lonely activity and even hard work, but if you have the passion, it’s worth it! It means you can have a positive impact in classrooms around the world where your case is taught.”

This infographic from The Case Centre shows the key demographic trends in the 2020/21 Top Bestselling Case Authors ranking. Courtesy Case Centre

WHERE TO TOP B-SCHOOL CASE STUDIES COME FROM

The UK- and U.S.-based Case Centre has released its bestselling case author list every year since 2016, ranking authors whose cases have sold the most copies during the previous academic year. This year, it raised the number of bestselling authors from 40 to 50.

Of this year’s list, authors came from 19 different business schools in nine separate countries. That includes 42% each from Europe and the United States, and 16% from Asia.

“As the list increases from 40 to 50, we see a change in the geographic dynamics,” the nonprofit announced. “European and U.S. schools each have a 42% share of the 2020/21 Top 50, down from 45% in 2019-20. While the representation of schools in Asia rises to 16%, up from 10% last year.”

Eighteen percent of the authors are women while 82% are men. While the list does not break down bestselling cases by the race, ethnicity or gender of its protagonists, finding case studies that represent the increasing diversity of business students (and in business executives) has been an ongoing concern for many B-schools’ diversity, equity, and inclusion efforts. For example, Harvard Business School published more than 70 cases with Black or African-American protagonists this past year after long-standing criticism that its studies ignored Black business leaders, according to a Poets&Quants article published in June .

It also produced 90 cases featuring Hispanic, Asian or Asian-American/Pacific Islander, or Native-American protagonists. HBS faculty write about 400 case studies per year.

“Our students are right that protagonist diversity matters,” Jan Rivkin, HBS senior associate dean and chair of the MBA program, said in June . “By studying cases with a wide diversity of protagonists, students learn that talent and leadership come from all backgrounds and identities. If students don’t understand that, they’ll worsen inequities, miss out on opportunities for themselves, and miss chances to create opportunities for others.”

DEBUT AUTHORS EARN TOP SPOTS

ICFAI Business School also had the No. 2 and No. 3 authors, and both are new entrants to the Case Centre’s list.

Second-ranked author Indu Perepu is an assistant professor specializing in human resource management. Her best-selling cases include “Airbnb: A Disruptive Innovator” and “Snapchat Turns Down Facebook’s Acquisition Offer.”

“What makes the case study method even more meaningful is that in developing countries like India where teaching through cases is picking up, case studies help the students with limited international exposure to learn intricately about multinational corporations and the world’s largest companies,” Perepu says.

Third-ranked author Syeda Maseeha Qumer is an assistant professor specializing in business strategy. For her top-selling cases, she looked at the integrated marketing strategy of HBO’s Game of Thrones and the impact of conflict palm oil on deforestation, human rights violations, and climate pollution, and PepsiCo’s use of it in its products.

“Case-based learning is unmatched in its ability to engage students and teach essential concepts that are relevant to practicing managers,” Qumer says. “Innovation in the case method is essential to enliven any classroom and to obtain better learning outcomes. I have always endeavored to develop diverse cases on contemporary issues that offer students an opportunity to explore complex real-world management challenges in the classroom, allowing them to assess their decision-making skills before taking the plunge into the corporate world.”

France’s ESSEC Business School had the top climbing author, Ashok Som , who moved up 26 places to No. 11 from last year’s ranking.

See the full list of this year’s case-writing winners on page 2, including links to their bios.

Harvard Business School is the home of the business case study. Once again it is also where most of the top-ranked cases were written in 2021

Beyond its ranking of case study authors, the Case Centre trains faculty in using case studies in B-school education, runs international case competitions and offers scholarships to unpublished case writers and teachers. Membership includes more than 500 business schools and organizations around the world.

See its full release and read about other best-selling authors here .

1. The Top 50 Bestselling Case Authors 2020/21 – full list

1 Debapratim Purkayastha , ICFAI Business School (IBS) 2 Indu Perepu , ICFAI Business School (IBS) 3 Syeda Maseeha Qumer , ICFAI Business School (IBS) 4 W Chan Kim , INSEAD (joint) 4 Renée Mauborgne , INSEAD (joint) 6 Joerg Niessing , INSEAD 7 Christopher A Bartlett , Harvard Business School 8 Wolfgang Ulaga , INSEAD 9 David B Yoffie , Harvard Business School 10 Nader Tavassoli , London Business School 11 Ashok Som , ESSEC Business School 12 Jill Avery , Harvard Business School 13 Kamran Kashani , Institute for Management Development (IMD) 14 Youngme Moon , Harvard Business School 15 Kasra Ferdows , McDonough School of Business, Georgetown University 16 John A Quelch , Miami Business School 17 David Dubois , INSEAD 18 Carlos Cordon , Institute for Management Development (IMD) 19 Michael Lewis , University of Bath School of Management (joint) 19 Jose A D Machuca , Universidad de Sevilla (joint) 21 David J Collis , Harvard Business School 22 Pierre Chandon , INSEAD 23 Mohanbir Sawhney , Kellogg School of Management 24 Robert F Bruner , University of Virginia Darden School of Business 25 Denis Gromb , HEC Paris 26 Urs Mueller , SDA Bocconi School of Management 27 Vivek Gupta , TechSci Research 28 Jamie Anderson , Antwerp Management School 29 Benoit Leleux , Institute for Management Development (IMD) 30 Sanjib Dutta , ICFAI Business School (IBS) 31 Vincent Dessain , Harvard Business School 32 GV Muralidhara , ICFAI Business School (IBS) 33 Jitesh Nair , ICFAI Business School (IBS) 34 Michael J Schill , University of Virginia Darden School of Business 35 Elizabeth Grasby , Ivey Business School 36 Horacio Falcão , INSEAD 37 Robert S Kaplan , Harvard Business School 38 Seán A Meehan , Institute for Management Development (IMD) 39 Herminia Ibarra , London Business School 40 Ian Dunn , Ivey Business School 41 Peter Killing , Institute for Management Development (IMD) 42 Stefan Michel , Institute for Management Development (IMD) 43 Jan W Rivkin , Harvard Business School 44 Inyoung Chae , Goizueta Business School, Emory University 45 Sean D Carr , University of Virginia Darden School of Business 46 James E Hatch , Ivey Business School 47 Thales Teixeira , Decoupling.co 48 Eric Van den Steen , Harvard Business School 49 V Namratha Prasad , ICFAI Business School (IBS) 50 P Fraser Johnson , Ivey Business School

DON’T MISS HOW TO REVIEW MBA CASE STUDIES LIKE AN EXECUTIVE and HARVARD BUSINESS SCHOOL FACULTY PUBLISHED 70 CASES WITH BLACK PROTAGONISTS THIS PAST YEAR

The post The Most-Read Case Studies Of 2021, And The Profs Who Wrote Them appeared first on Poets&Quants .

Breakthroughs and Discoveries in Psychological Science: 2020 Year in Review

• Psychological Science

Many of the major news stories of 2020 were closely tied to understanding human behavior, including efforts to contain the spread of COVID-19, understand political divides and social conflicts, and address enduring racial disparities and inequality.  

A wealth of research published by the Association for Psychological Science (APS) addresses these and other important topics. The following is a selection of some of APS’s most newsworthy research and highly cited publications from 2020. These stories emphasize the importance of peer-reviewed psychological research and its impact on society.  

Top 10 APS News Releases of 2020, Metrics Provided by  Newswise  

Romance, Scent, and Sleep: The Stuff that Dreams Are Made Of : Research published in the journal  Psychological Science  suggests that the scent of a romantic partner can improve your quality of sleep. This is true regardless of whether you are consciously aware that the scent is even present.  

Violent Video Games and Aggression: The Connection Is Dubious, at Best : The coronavirus pandemic put a damper on many traditional summertime activities for kids, giving them more opportunity to socialize with friends virtually through online gaming. But many hours of extra screen time worried some parents, especially in light of a 2015 report linking violent video games with aggressive behavior in children. A reanalysis of previous findings published in the journal  Perspectives on Psychological Science  found no clear link between video game violence and aggression in children. 

Stemming the Spread of Misinformation on Social Media : The dangers of COVID-19 could worsen if misinformation on social media continues to spread unchecked, according to research published in  Psychological Science . Though there is no practical way to fully stem the tide of harmful misinformation on social media, certain tactics could help improve the quality of information that people share online about this deadly disease. 

Psychological Science and COVID-19: Conspiracy Theories : Why are conspiracy theories so popular? Who believes them? Why do people believe them? What are some of the consequences of conspiracy theories, and can such theories be harmful? These questions are explored by Karen Douglas, professor of social psychology at the University of Kent, UK, whose research focuses on beliefs in conspiracy theories.  

Pandemic Effects on Marriage and Relationships : Beyond its economic toll, COVID-19 is also having a negative impact on many relationships. Expert commentary from Paula Pietromonaco, professor emerita at the University of Massachusetts, Amherst, explores this facet of the pandemic and how interactions in marital and other close relationships shape each partner’s emotional and physical health. 

Trigger Warnings Fail to Help and May Even Harm : A study published in the journal  Clinical Psychological Science  shines light on the value and potential harm of trigger warnings, the term used to alert readers or viewers to potentially unsettling content. This research suggests that trigger warnings offer little to no help in avoiding painful memories and can even be harmful for the survivors of past emotional trauma.  

Contracting COVID-19: Lifestyle and Social Connections May Play a Role : Research published in  Psychological Science  indicates that unhealthy lifestyle choices, including smoking and lack of exercise, along with emotional stressors like social isolation and interpersonal conflicts are important risk factors for developing upper respiratory infections. It is possible these same factors also increase the risk of contracting COVID-19. 

Does Bedtime Media Use Harm Children’s Sleep? Only If They Struggle to Self-Regulate Behavior : Throughout the COVID-19 pandemic, one concern for many parents has been the impact of additional TV or computer screen time on their children and their already disrupted sleep habits. A study published in  Psychological Science  found that media use in the hour preceding bedtime impacts the sleep only of children who struggle to self-regulate their behavior. 

Health and Happiness Depend on Each Other, Psychological Science Says : This research adds to the growing body of evidence that happiness not only feels good, but it is also good for your physical health. Research published in  Psychological Science  shows that both online and in-person psychological interventions—tactics specifically designed to boost subjective well-being—have positive effects on self-reported physical health.  

Claiming Journalism Is ‘Fake News’ May Satisfy a Personal Need for an Orderly World : Research published in  Psychological Science  reveals that the degree to which people level accusations of fake news against news outlets is at least partially associated with a personal need for an orderly and structured environment. 

Top 10 APS Journal Articles Based on  Altmetric Attention Scores  

Aging in an Era of Fake News : Older adults appear to be particularly susceptible to misinformation (e.g., they shared the most fake news during the 2016 U.S. election). In  Current Directions in Psychological Science , researchers suggest that social changes in late adulthood, including difficulty in detecting lies and less emphasis on accuracy when communicating, might be partly responsible for susceptibility to misinformation. Moreover, older adults are less experienced with social media and may struggle to evaluate the veracity of content. Interventions that take into account older adults’ social changes and digital literacy might help to reduce their susceptibility to fake news.     Sex Differences in Mate Preferences Across 45 Countries: A Large-Scale Replication :  Research published in  Psychological Science  seems to support the popular perception that men are more likely to prefer attractive young mates, and women are more likely to prefer older mates with financial prospects. These sex differences were universal across the 45 countries surveyed. In countries where gender equality was higher, both sexes appeared to have mates closer to their own age. Contrary to older studies, this study found that gender equality did not predict other differences in mate preferences, such as financial prospects. Also, different countries’ rates of communicable and infectious diseases did not predict sex differences or preferences. 

What Is the Test-Retest Reliability of Common Task-Functional MRI Measures? New Empirical Evidence and a Meta-Analysis : The reliability of measuring brain activity using task functional MRI (fMRI) for predicting disease risk and outcomes appears to be low. In  Psychological Science , researchers present a meta-analysis of prior research and an analysis of test-retest reliability of brain activity in certain regions across 11 common fMRI tasks. The authors found that reliability across studies was low, and test-retest studies did not reliably show activity in the same areas of interest for the same tasks. These findings suggest that current task-fMRI measures are not suitable for predicting clinical outcomes or studying individual differences.    Racial Inequality in Psychological Research: Trends of the Past and Recommendations for the Future :  Systematic inequality exists within psychological research.  This is the conclusion researchers published in  Perspectives on Psychological Science  after querying more than 26,000 articles published between 1974 and 2018 in top-tier psychology journals. Most publications are edited by White editors, and the few publications that highlight race were written by White authors and had few participants of color. These findings suggest the need to diversify editing, writing, and participation in psychological science. To this end, the researchers provide a set of actionable recommendations for journals and authors.  

Your Brain Is Not an Onion With a Tiny Reptile Inside : A paper in  Current Directions in Psychological Science  describes a model of neural evolution that challenges the widespread misconception that as vertebrate animals evolved, they added “newer” brain structures to the “older” existing ones, enabling them to have more complex psychological functions (e.g., language). Neurobiologists have long discredited this misconception that the reptile brain is still part of the human brain, which just added more layers. The authors provide examples of how this inaccurate view of brain evolution has impeded progress in psychology. 

The Emotional Path to Action: Empathy Promotes Physical Distancing and Wearing of Face Masks During the COVID-19 Pandemic : Empathy for people most vulnerable to COVID-19 appears to motivate wearing face masks and practicing social distancing, according to an article published in  Psychological Science . Participants who showed more empathy for the most vulnerable to the virus were more likely to report social-distancing practices. In two experiments, inducing empathy resulted in higher motivation to wear face masks and to practice social distancing than simply informing participants about the importance of these practices, in particular for those most vulnerable to the virus.  

Fighting COVID-19 Misinformation on Social Media: Experimental Evidence for a Scalable Accuracy-Nudge Intervention :  Nudging people to think about the accuracy of news headlines might be a simple way to improve their choices about what to share on social media. When directly asked about the accuracy of COVID-19-related news, participants in a study published in  Psychological Science  were better at discriminating between true and false than when asked simply to decide whether to share it. Similarly, having participants judge the accuracy of non-COVID-19-related headlines increased their discernment about the accuracy of COVID-19-related articles and the quality of their subsequent intentions to share them.  

How Firm Are the Foundations of Mind-Set Theory? The Claims Appear Stronger Than the Evidence : Mind-set theory proposes that the beliefs one has about whether attributes are malleable ( growth mind-set ) or unchangeable ( fixed mind-set ) influence one’s motivation, type of goals, persistence, and resilience. Contrary to what the mind-set theory would predict, researchers publishing in  Psychological Science  tested 438 students and found weak associations (<.20) between mind-set, goal orientation, response to challenge, belief in effort, cognitive ability, and intelligence. The researchers suggest that these results may indicate that some claims about mind-set might be overstated. 

The Future of Women in Psychological Science :  A team of researchers analyzed 10 topics relevant for women’s professional prospects in psychological science: career advancement; financial compensation; service assignment and practices; lifestyle roles and work–family conflict; gender biases; prevalence and perceptions of positions of power; intersectionality; harassment and incivility; agency, self-esteem, and self-promotion; and lack of belonging. In  Perspectives on Psychological Science , the authors discuss empirical evidence for each of these issues and clarify gender gaps and positive change in the hope that a better understanding of these issues will spark conversation and help to mitigate remaining gender differences in the field. 

Can Bad Be Good? The Attraction of a Darker Self : We prefer fictional villains who are similar to us, according to research in  Psychological Science . Researchers explored data from an online platform that allows users to become “fans” of characters and take a quiz to evaluate their similarity with them. Individuals preferred villains who were similar to themselves. A series of laboratory studies also found an association between similarity of negative traits, when the villain was fictional but not when the villain was a real person, and attraction to the villain. 

Stories in Action

Stories may complement established policy tools. Walsh and colleagues define the elements of storytelling and discuss stories’ key features and functions, providing design principles for policymakers interested in building stories. 

SAGE 10-Year Impact Awards Honor Two APS Articles

Two 2011 APS journal articles exploring the rise of Amazon Mechanical Turk (MTurk) and the risk of accepting false-positive findings have received SAGE Publishing’s third annual 10-Year Impact Awards.

Letter from the Editor: A New Chapter for the Observer

After nearly 40 years in print, the APS member magazine is going all-digital.

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Recent case studies on the use of ozone to combat coronavirus: Problems and perspectives

Soumya nagashri manjunath.

a Ohio Heart Group, 800 East Broad Street, Columbus, OH 43205, USA

b Centre for Nano and Material Sciences, Jain University, Bangalore 562112, Karnataka, India

Manmohan Katapadi

c Ohio University, Ohio Heart Group, Ohio Health systems and Mount Carmel Health systems, 800 East Broad Street, Columbus, OH 43205, USA

R. Geetha Balakrishna

Coronavirus pandemic has created havoc in the world. COVID-19 is now officially labeled as Severe Acute Respiratory Syndrome-related Coronavirus-SARS-CoV-2. Therefore, it is equally important to combat the virus both inside the human body as well as in the environment. These viruses, being RNA viruses, are found to be susceptible to ozone. Ozone being an unstable molecule can breakup into its split products namely reactive oxygen species and ozonides creating a toxic environment for these viruses. Ozone mainly prevents the membrane fusion with the host cell, thus interfering with their replication. With vast applications of the gas, it has created a new spark in the field of medicine in combating these viruses and many other organisms. In this context, this article provides insights from recent clinical and research studies on the problems and possibilities in employing the ozone to combat the coronaviruses.

Graphical abstract

1. Introduction

Coronaviruses, the reason for this pandemic, are RNA viruses which are mainly spread by human to human contact by respiratory droplets generated via coughing, sneezing and many other sources as well ( Harapan et al., 2020 , Coccia, 2020a , Wang et al., 2020b , Rubio-Romero et al., 2020 ). Typically, these viruses generally do not travel over 6 ft and do not remain much in the air, however some reports also suggest that they remain viable on many inanimate objects up to several hours ( Harapan et al., 2020 ). The penetration capacity of ozone is quantified to be more than that of most of the liquids used as cleansing agents (used to prevent infections) ( de Wit et al., 2016 ). Ozone causes peroxidation of the infected cells and also damages the viral capsid. It thus can disrupt its reproductive cycle. Meanwhile, the infected cells, with peroxidized weak enzyme coatings (which have already succumbed to the virus), eventually get exposed to oxidation in the cellular apparatus of the host and finally get eliminated during the process. They are then replaced by the healthy cells in the body. Ozone can be toxic to lungs and eyes depending on the concentration, temperature, humidity and exposure time, which can result in cough and irritation in the throat ( Di Paolo et al., 2004 ). Furthermore, pulmonary edema can also be caused by high concentrations in bronchial mucosa and pneumocytes ( Di Paolo et al., 2004 ). A concentration of 0.02 μ g/mL can be fatal and cause death in 4 h ( Di Paolo et al., 2004 ). Blood of elderly and immune compromised may need administration of fortified reducing agents before administration of ozone ( Bocci, 1992 ).

Coronavirus is viable on inanimate surfaces for 9 days, are temperature dependent and can be easily inactivated by oxidation processes induced by oxidizing agents ( Rowen and Robins, 2020 ). It has been proposed by Coccia that high concentration of air pollutants and low wind speed allows longer persistence of viral particles in air. Density of population in a locality and respiratory disorders people suffer from, also plays a major role in spread of infection ( Coccia, 2020b ). Further, according to this study, the ozonides, which are the byproduct of ozone are themselves potent oxidants with long half-life and can help in degrading viral cysteine residues ( Li, 2016 ). To this end, this review essentially characterizes the suitability of ozone in combating the corona viruses in the perspective of treating the real time COVID-19 patients, which are presented as cases studies and other possible uses establishing the role of ozone in combating the coronaviruses in environment. To begin with, the chemical framework of the virus and the role played by each of its structural components in establishing the disease in humans is discussed. Notably, the ACE2 receptors in humans play important role to get infected with the disease by binding to the spike proteins present in the lungs, respiratory system, which becomes the main target for its pathology ( Li, 2016 ). The TMPRSS211, a serine protease, also plays a vital role in priming the S protein, which is the initiator of disease transmission. Moreover, many cytokines such as IL-6, G-CSF also promote the pathology and are further assisted by many signaling pathways such as nuclear factor kappa beta and JAK-STAT pathways. Similarly, the VEGF and EPO also promote the neoangiogenesis and atherogenesis, and resulting in cardiovascular complications ( Zhang et al., 2020 ). To combat this, it is found that the ozone when given by autohaemotherapy, it dilutes in blood and forms lipid oxidation products and ozonides, which activate many signaling pathways like hypoxia inducible factor 1 – alpha and nuclear factor kappa beta ( Zhang et al., 2020 ). Thereby, it activates many cytokines, glycolytic pathways to enhance ATP, enzymes such as superoxide dismutase and glutathione peroxidase to enhance the intracellular killing of the infected cells. Furthermore, the use of ozone in many conditions including peripheral vascular diseases and neurodegenerative conditions may be of use for future research.

2. Overview of corona viruses

2.1. structure.

Coronavirus is a positive-sense, single-stranded RNA virus of 27–32 kb in size ( Li, 2016 ), with club-like spikes giving them crown like appearance and a large RNA genome in a helical capsid formed by nucleocapsid protein (N) ( Rowen and Robins, 2020 , Li, 2016 , Cynthia et al., 2020 ). They are enveloped, pleotropic viruses ( Weiss and Navas-Martin, 2005 ) and found to have cysteine in their membranes essential for membrane fusion ( Rowen and Robins, 2020 , Cynthia et al., 2020 ). They belong to the family Coronavirinae subfamily Coronaviridae ( Fehr and Perlman, 2015 ). The virus has mainly 4 structural proteins, known as spike (S), membrane (M), envelope (E) and nucleocapsid proteins ( Fig. 1 ). The M protein and E protein are involved in viral assembly and spike protein is involved in allowing viral entry into the host cells, has a range of viral host, tissue-tropism and is a main stimulator of the immune responses in the host ( Li, 2016 ). Spike protein has 3 segments; a short intracellular tail, a single-pass transmembrane anchor, and a large ectodomain. The ectodomain is composed of receptor-binding subunit (S1) and membrane fusion subunit (S2). S1 subunit binds to the receptor on the host cell surface during the process of viral attachment and a S2 subunit fuses the viral to the host cell membrane ( Li, 2016 , Catanzaro et al., 2020 , Tizaoui, 2020 ). The envelope also contains arachidonic acid, linoleic acid (important for the disease pathology), palmitic acid, oleic acid and glutamic acid. They also have glycoproteins in the Spike component and are further accompanied by heterogeneous N-linked glycans, which act as the pivotal focus for the action of antibodies ( Tizaoui, 2020 ). Coronaviruses have many sub classifications, among them; SARS Cov and HCov have found their way to the humans. The other subclasses are found to affect many other animals like turkeys, pigs and so on ( Weiss and Navas-Martin, 2005 ).

Structure of viral spike protein [ https://www.cas.org/blog/covid-19-spike-protein ].

2.2. Classification and functions

Coronaviruses are mainly classified into 4 classes - α , β , γ , δ subtypes. β coronaviruses are further classified into SARS and SARS-CoV, Middle Eastern Respiratory Syndrome virus (MERS and MERS CoV) and COVID-19 causative agent SARS CoV-2. These SARS CoV-2 viruses contain many structural proteins of which the glucosylated spike (S) protein induces the immune response system of the host. S protein binds to a protein receptor known as the Angiotensin Converting Enzyme 2 (ACE 2) situated on the surface-membrane of the host cells mainly in the pulmonary tissues. This binding has a higher affinity when compared to the binding of SARS CoV and hence has higher transmissibility and contagiousness. The process f invasion also requires spike (S) protein priming, which is mainly carried out by host cell which produces serine protease TMPRSS211. The viral-genome has many other non-structural proteins like RNA — papain like protease (PLpro), coronavirus main protease (3CLpro) and dependent RNA polymerase (RdRp). Once the virus invades, it gains entry into the host cell as a single-stranded, positive sense-RNA. After gaining entry into the cytosol, the virus starts replicating inside the cell by using replicase ( Fehr and Perlman, 2015 ). This is followed by translation of viral polyproteins by using host cell protein translator machinery ( Fig. 2 ). The product of translation is then sliced into effector-proteins by viral proteinases 3CLpro and PLpro. PLpro then deubiquitinises particular host cell proteins like INF factor 3 and NF- κ β and causes host immune-suppression. RdRp synthesize full-length negative stranded RNA template to make more viral genome, thus helping in viral replication ( Li, 2016 , Cynthia et al., 2020 , Fehr and Perlman, 2015 ).

Pathways of SARS-CoV-2 [ https://www.cas.org/blog/covid-19-spike-protein ].

These viruses are also known for homologous and non-homologous recombination ( Fehr and Perlman, 2015 ). Assembly and packaging inside the cell results in the formation of new viruses, ready to be released out and infect other cells. The viruses get released in the form of vesicles and get transported to the neighboring cells, but the S protein does not get incorporated in to the virus particle, making it going undetected by the virus-specific antibodies and helps in the creation of multinucleated giant cells ( Fehr and Perlman, 2015 ).

2.3. Disease pathology

Coronaviruses mainly attack the immune system by stimulating a cytokine storm (hypercytokinemia), which leads to plasma leakage, vascular permeability and disseminated intravascular coagulation. This cytokine storm results in high plasma levels of IL-1 β , IL-1ra, IL-7, IL-8, IL-9, IL-10, basic FGF, G-CSF, GM-CSF, IFN- γ , IP-10, MCP-1, MIP-1 α , MIP-1 β , PDGF, TNF α , VEGF which injure the lung tissue. Hence the uncontrolled release of cytokines results in a ‘cytokine storm’ resembling Systemic Inflammatory Response Syndrome coupled with additional viral and bacterial infections because of dysregulated immunity, finally resulting in multiorgan failure and death ( Catanzaro et al., 2020 ).

ACE2 is mainly expressed in alveolar epithelial type II cells to facilitate replication of coronaviruses. They are also found in extra-pulmonary sites like heart, kidney, endothelium, and intestine (intestinal epithelial cells as a co-receptor for nutrient uptake) ( Coccia, 2020b ). The binding of viral spike protein to host cells by ACE2 receptor triggers the detection of viral RNAs as Pathogen Associated Molecular Patterns (PAMPs) through pattern recognition receptors. These receptors belong to a family of Toll like receptors. This recognition happens through endosomal RNA receptors like TLR3 and TLR7/8 and cytosolic RNA sensor, retinoic acid-inducible gene (RIG-1)/MDA5. These TLRs activate signaling pathways in human CD 14+ monocytes and CD4+ T cells which include (a) IFN regulatory factor-3 which stimulate cytokines and chemokines, (b) Nuclear factor κ β and (c) JAK (Janus Kinase) STAT (Signal Transducer and Activator of Transcription). Nuclear factor κ β is normally inhibited by inhibitory proteins like I κ β s. SARS CoV2 causes degradation of I κ β α , thus activating NF κ β . NF κ β further causes activation of pro-inflammatory cytokines, chemokines, stress-response proteins and anti-apoptotic proteins. NF κ β is also activated by IL-6 and TNF α  ( Catanzaro et al., 2020 ).

JAK-STAT Pathway: Membrane bound IL-6 receptor and soluble form of IL-6 receptor which interacts with gp130 promotes the activation of JAK-STAT signaling. The signaling pathway is further enhanced by reactivation of IL-6. IL-6 produced by macrophages, endothelial and smooth muscle cells, promotes the secretion of cytokines like MCP-1, which induce atherogenesis further increasing the expression of cell adhesion molecules and stimulating the proliferation and migration of vascular smooth muscle cells. Inflamed cells further increase expression of ATII receptor, and its binding to ATII, which further activates IL-6 in a reciprocal manner, finally activating the JAK-STAT pathway ( Catanzaro et al., 2020 ).

The ACE2 receptor which helps in priming of viral cells is down regulated by the binding of viral spike protein, which results in overproduction of ATII, finally causing vascular inflammation and lung injury as mentioned before. ATII/ATII receptor axis also activates NF- κ β and ADAM17, and ADAM17 inactivates ACE2, hence amplifying ATII. ADAM17 is also known to process membrane form of IL-6 receptor α , which forms soluble form SIL-6R α via SIL-6R α -IL-6 complex which is also mediated by gp130. This reaction further activates STAT3 which finally activate NF- κ β in a variety of negative non-immune cells. Hence the signaling pathways interact with each other, to induce their co-activation. Further IL-6 provides a feedback loop and helps in amplifying many myeloid and lymphoid cells. ADAM17 in presence of ATII,trans-activates EGFR which stimulates the mature form of heparin to bind to EGF-like growth factor in vascular smooth cells which causes vascular remodeling ( Catanzaro et al., 2020 ).

2.4. Symptomatology

Coronaviruses are found to be very contagious and can result in a lot of respiratory symptoms. HCoV-NL63 a strain of human coronavirus can result in acute laryngotracheitis (croup). Many coronaviruses on a long run have found to predispose to Multiple sclerosis. The COVID 19 has mainly affected men, patients with underlying comorbidities like diabetes, hypertension, cardiovascular diseases and other immune compromised states. Median age was found to be around 49 years, but in general any individual above 60 years have been found to be at risk for the infection ( Harapan et al., 2020 , Chaolin et al., 2020 ).

Common symptoms were found to be fever, cough, and myalgia or fatigue; less common symptoms were sputum production, headache, hemoptysis, and diarrhea. Dyspnea and lymphopenia were also found to be present in few patients. Most patients were found to have pneumonia picture that is patchy opacity to ground glass appearance on CT chest ( Harapan et al., 2020 , Chaolin et al., 2020 ). Imaging suggests that the virus commonly affects lower lobes in their peripheral location bilaterally ( Harapan et al., 2020 ). The complications encountered include acute respiratory distress syndrome, acute cardiac injury and secondary infection. When a comparison was made between non-ICU and ICU patients, the later had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNF α ( Chaolin et al., 2020 ).

The diagnosis of coronavirus is based on antigen detection of specific strain of coronavirus through the nasopharyngeal swab, and the genetic material RNA is mainly detected via blood and urine ( Harapan et al., 2020 ). Although no specific treatment measures are available so far. However, - Favipiravir, Lopinavir–Ritonavir, Ribavirin and Interferon have shown to provide some relief to few patients with elderly patients requiring ventilators, once diagnosed with the disease ( Harapan et al., 2020 , Chaolin et al., 2020 ). Additionally, Remdesivir and hydroxychloroquine have also been found to show potent antiviral activity recently ( Harapan et al., 2020 , Cynthia et al., 2020 ).

3. Overview of ozone (O 3 )

3.1. chemistry of ozone.

Ozone is a gas composed of trioxygen and is unstable molecule due to its mesomeric states. It is acrid in odor, a colorless-transparent gas, explosive in liquid and solid form, has a half-life of 40 min at 20 °C and about 140 min at 0 °C. Ozone occurs at less than 20 μ g/m 3 from the surface of the earth, and mainly provides protection against UV radiation coming from the sunrays ( Di Paolo et al., 2004 ). The medical grade ozone is composed of pure O 2 and pure O 3 in the ratio of 0.1%–5% and 95–99.5% respectively ( Rowen and Robins, 2020 , Komali, 2012 ). Ozone can be produced by one of the three means by ultra-violet system (produces only low amount of O 3 ), by cold plasma system and by corona discharge system (produces high amount of O 3 ) ( Komali, 2012 , Elvis and Ekta, 2011 ). Ozone has high affinity for double covalent bonds like C—C, which are present in polyunsaturated fatty acids that are carried by albumin molecules. Hence these results in creation of ozone molecules with longer half life called ozonides — ROS and lipid oxidation products like peroxides, hydroperoxides and aldehydes. They act as messengers of biochemical and immunomodulatory effects of ozone ( Hernández et al., 2020 ).

3.2. Medical uses of ozone

Ozonized water is used as a spray or a compress; and used in dental medicine, geriatric developments, circulatory disorders, viral diseases, macular degeneration, rheumatism/arthritis, infected-wounds, AIDS, SARS and cancer. It also decreases the blood cholesterol, has antioxidant responses, used in treatment of hypoxic, it modifies the oxygenation in resting muscle and used in complementary treatment of ischemic syndromes ( Elvis and Ekta, 2011 ). It has been shown that a single subcutaneous injection of ozone in mouse with spared nerve injury of sciatic nerve reduces neuropathic pain ( Elvis and Ekta, 2011 ).

(a) Peripheral obstructive arterial diseases : Ozone induces glycolysis to increase ATP and 2, 3-DPG. This causes a shift in the sigmoidal O 2 – binding curve of hemoglobin to right in turn resulting in release of O 2 in ischemic tissues. This results in conversion of H 2 O 2 to H 2 O in RBC in presence of GSH. This reaction is mainly responsible for healing ischemic tissues and has been shown that even stage IV of the disease, where there is necrosis of toes and unbearable pain can be delayed by ozonated AHT in 50%. Ozone also stimulates HO-1, HSP70 and Nrf2 which induce antioxidants, nuclear transcription factor and hypoxia inducible factor - 1 α (HIF – 1 α ). This induces VEGF, EPO and glycolytic enzymes to promote cell proliferation and survival. VEGF induces neo-angiogenesis to increase the blood flow which further increases EPO to enhance oxygen delivery. Moreover the glycolytic enzymes promote metabolism of glucose to increase the biosynthesis of NO and CO which also increase the blood flow and oxygen delivery to hypoxic tissues ( Sagai and Bocci, 2011 ).

(b) Age-related macular degeneration : The condition is mainly caused by death of photoreceptors in fovea centralis and of pigmented retinal epithelium to cause chronic hypoxia. Ozone (AHT) helps by increasing the delivery of oxygen to retina ( Sagai and Bocci, 2011 ).

(c) Diabetes mellitus : Ozone is found to reduce HbA 1 C, CRP, nonenzymatic glycosylation, aldose reductase activity, advanced glycated end products and antioxidant–prooxidant​ balance ( Sagai and Bocci, 2011 ).

(d) Cancer : In a study by Sweet et al. it was shown that when an experimental attempt was done to insufflate an ozone and oxygen mixture into the peritoneum, it led to higher rate of survival of treated rabbits ( Sagai and Bocci, 2011 ).

(e) Neurodegenerative diseases : Nrf2 and HIF - 1 α induced by ozone through activation of HO-1 play an important role in neuroprotection and suppression of neuro-inflammation in neurodegenerative diseases ( Sagai and Bocci, 2011 ).

(f) Skin and mucosal infections : Ozone is used in diabetic foot, ischemic ulcers, necrosis, decubitus, abscesses, anal fissures, fistulae, aphthous stomatitis, osteomyelitis, stomatitis, vulvovaginitis and onychomycosis ( Sagai and Bocci, 2011 ).

(g) Backache and orthopedic diseases : when 30–35 μ g/ml of ozone is directly administered into the center of intersomatic space corresponding to disc herniation, it dissolves in the water of nucleus pulposus and reacts with macromolecular glycoproteins composed of carbohydrates and polypeptide chains (proteoglycans, collagen II and IV). This generates OH − which reabsorbs hydrolytic products and free water, thus causing shrinkage of nucleus and disappearance of herniated material ( Sagai and Bocci, 2011 ).

3.3. Mechanism of ozone in killing the viruses

Ozone disrupts viral proteins, lipoproteins, lipids, glycolipids, or glycoproteins, making them susceptible to oxidizing effect and participates in redox reactions. It also damages the viral envelope glycoproteins and peplomers, which are essential for the attachment of virus to host receptors. Coronaviruses contain cysteine residues in their spike and envelope proteins ( Rowen and Robins, 2020 ). These cysteine residues are made of sulfhydryl groups called thiol groups (R-SH). These thiol groups in a reduced state in the virus play a pivotal role in the viral entry and viral membrane fusion with the host cell membrane as described in the viral structure. Hence, when ozone reacts with these thiol groups/sulfhydryl groups, it oxidizes them into to sulphonic acid residues (R-SO 3 -H) as shown in Fig. 3  ( Fernández-Cuadros et al., 2020 ). This process can be enhanced at higher temperatures. Ozone by altering these cysteine residues decreases the growth of the virus by 2 log lower than the wild type virus ( Rowen and Robins, 2020 ). In addition, coronaviruses have a cysteine dependent papain (a cysteine dependent protein enzyme) which is oxidized and degraded to sulfonate/sulphonic acid.

Mechanism of ozone in preventing the binding of S-spike protein residues to the ACE2 receptor ( Fernández-Cuadros et al., 2020 ).

The spike proteins also have tryptophan which can be degraded by ozone ( Rowen and Robins, 2020 , Fernández-Cuadros et al., 2020 ). Ozone incorporation into the serum of the human body produces lipid and protein peroxides which have antiviral effects. Ozone also alters viral envelope and viral genome significantly enough resulting in nonpathogenic dysfunctional viruses. These attenuated viruses help in evoking a unique immunological response to various strains of a particular virus creating a host-specific auto vaccine ( de Wit et al., 2016 , Bocci, 1992 ). Besides the antibodies produced in the body to respond to any virus itself, it produces many highly active forms of ozone. Therefore, the addition of ozone essentially enhances the antigen–antibody response against viral infections in the host ( Di Paolo et al., 2004 ).

3.4. Mechanism of therapeutic actions of ozone

In blood, ozone combines and gets dissolved in the plasma propagating the decomposition of the gas into a variety of reactive oxygen species like superoxide anion ( O 2 • ¯ ), hydrogen peroxide (H 2 O 2 ) and hydroxyl radical (OH • ) ions ( Di Paolo et al., 2004 , Elvis and Ekta, 2011 ). Moreover, the peroxidation of plasma lipids results in formation of Lipid Oxidation Products (LOPS) ( Di Paolo et al., 2004 ). The above two mechanisms mainly help in enhancing the defense mechanisms ( Di Paolo et al., 2004 , Azuma et al., 2014 ). Ozone activates cytoplasmic transcription factors by secondary messengers like (a) hypoxia-inducible factor 1- α (HIF-1 α ), (b) Nuclear factor kappa beta (NF- κ β ) and (c) Nuclear factor erythroid – 2 – related factor 2 (Nrf2) ( Hernández et al., 2020 ).

In addition to the above, there is also production of hyper soluble antioxidants ( Di Paolo et al., 2004 ) and ozonides ( Rowen and Robins, 2020 ). The hydrogen peroxide produced by oxidizing effect of ozone mainly results in shifting the hemoglobin dissociation curve in the RBCs to the right and releasing oxygen, inducing glycolysis which increase ATP, thus reducing hypoxia ( Rowen and Robins, 2020 , Hernández et al., 2020 ). They also cause production of interleukins (IL-6), interferon gamma (antiviral action) ( Rowen and Robins, 2020 ), TNF, TGF, nitrogen oxide in the leukocytes, release of growth factors in platelets, and propagates the antioxidant effect in all cells ( Di Paolo et al., 2004 , Bocci, 1992 ). Ozone also stimulates Kreb’s cycle enhancing the oxidation carboxylation of pyruvate to produce ATP, reduces the amount of NADH, thus promoting the oxidation of cytochrome C, production of a vasodilator and prostacycline, activation of glutathione peroxide, catalase and superoxide dismutase ( Rowen and Robins, 2020 , Elvis and Ekta, 2011 ).

Ozone also activates the macrophages and neutrophils, accelerates the manifestation of major histocompatibility complex (MHC) Class I and II on diseased cells, lymphocytes and monocytes, and is also responsible for the improvement of cyto-toxicity either antibody-mediated or MHC-inhibited, or via natural killer (NK) cells enhancing the immune responses against many micro-organisms including viruses ( Bocci, 1992 ). Ozone by activating H 2 O 2 in neutrophils and lymphocytes causes activation of tyrosine kinase which phosphorylates NF- κ β , thus activating cytokines ( Hernández et al., 2020 ). Effect of ozone on lung tissue can be varied. Ozone can increase specific and mean airway resistance and respiratory rate, and also reduce the maximal trans-pulmonary pressure and tidal volume ( Elvis and Ekta, 2011 ). Ozone when given at appropriate dosage levels, mainly adds on to the preexisting oxidative stress in the body thus reaching the calculated dosage necessary to combat the infections. It is thus said to have a precise therapeutic window ( Di Paolo et al., 2004 ). Therefore, very low doses are not effective as they are masked by the existing antioxidants and very high doses can be toxic mainly to the pulmonary system. In terms of atherosclerosis, chronic viral infections, neurodegenerative diseases, tumor growth and aging; ozone administration can actually balance and maintain the antioxidant levels in the body, while the endogenous ROS go down during chronic oxidative stresses. Furthermore, it can also slow down the process of depletion of endogenous ROS and hence a long term calculated therapy with ozone can restore their levels in the body in the above mentioned conditions ( Di Paolo et al., 2004 ). If the period of stress continues, ozone therapy can enhance the production of existing heat-shock proteins (HSP), glucose-regulated proteins (GRP) and oxidative shock proteins (OSP) ( Di Paolo et al., 2004 ). O 2 - O 3 acts on nitric oxide and iNOS signaling pathways. NO inhibits palmitoylation of S (spike) protein of SARS CoV2, hence prevents the binding of S protein to ACE2 receptor primarily in lung tissue ( Franzini et al., 2020 ).

Ozone therapy (OT) utilizes around 1 to 5% ozone in 95 to 99% trioxygen as a gas (around 10 to 70 mcg ozone/cc gas). This blend is called “medical ozone” ( Rowen and Robins, 2020 ). It is suggested that ozone in the form of autohemotherapy can combat infections ( de Wit et al., 2016 , Di Paolo et al., 2004 ), where the minor ozone autohemotherapy and major ozone autohemotherapy involves the use of 5 to 10 mL and 200 to 250 mL of blood respectively as described by Wolff in 1974. The process is relatively straightforward: first, blood will be collected in a glass having sodium citrate of heparin, kept in vicinity of O 2 ∕ O 3 mixture at concentrations varying from 15 to 80 μ g/mL for around 5 to 10 min and then reinfused into the intend patients. This is typically carried out two times a week for about 7 to 8 weeks. Besides being used in various vascular and cardiovascular diseases, it is found to be effective in chronic viral infections like Herpes Zoster, Hepatitis, Herpes I and II, Acinetobacterbaumanni, C.difficile, MRSA ( Elvis and Ekta, 2011 ) and also in fungal and bacterial infections ( Di Paolo et al., 2004 , Rowen and Robins, 2020 ). It is also seen that activation of immunity occurs at 30–55 μ g/cc ( Elvis and Ekta, 2011 ).

Ozone is also said to have anti-hypoxic effects wherein, (i) it improves the transportation of oxygen and in cellular metabolism like glycolysis, Krebs cycle, (ii) it induces negative charge in RBCs increasing the blood cell elasticity and (iii) it improves the metabolism of inflamed tissues by increasing their oxygenation and reduces local inflammatory processes ( Gupta and Mansi, 2012 ). It also increases the synthesis of ribosomes, and mitochondria in the cells thus enhancing aerobic respiration and enhances the protein anabolism. Ozone is also known for the increased production of NO which helps in vasodilation of arterioles and veins and also in angiogenesis ( Gupta and Mansi, 2012 ).

3.5. Proposed dosage of ozone and related evidences

Ozone is not toxic when it is given at concentrations of 0.05 ppm for a continuous period of 8 h ( Gupta and Mansi, 2012 ). Ozone is found to play a major role in the field of endodontics and prosthodontics. In a study conducted by Komali (2012) , ozone was used as oil to lubricate, and irrigate the canals of the teeth, and was later used at a concentration of 30 ml to slowly insufflate the canals for 45 to 60 s This resulted in activation of fibroblasts and increased the activity of healing. In another study by the same author, the gram positive and gram negative bacteria were killed by 0.5–4 mg/l of ozonized water in the oral mucosa ( Komali, 2012 ). The study also states that using 20 mg/h of ozone reduces the Methicillin-resistant Staphylococcus aureus (MRSA) and E-coli T1 phage virus bacteria from 3.1  ×  10(3) CFU/mL to 1.0  ×  10(0) CFU/mL in 10 min later during the oral activity ( Komali, 2012 ).

4. Case studies

4.1. ozone gas as a virus decontaminating agent.

Hudson et al. (2009) have developed an ozone gas-based portable apparatus to decontaminate the buildings such as the rooms in health-care facilities, hotels, etc using the anti-viral properties of ozone. They tested against 12 viruses, which include influenza, strain H3N2, etc., and including the mouse coronavirus (MCV) in DBT cells. They observed that at the peak ozone gas concentration of 20–25 ppm, it required only a short-period of high-humidity (relatively humidity of > 90%) to reach the maximum anti-viral efficacy.

Furthermore, their experiment also emphasized that the nature of surface on which the samples containing the inoculum was placed did not affect the result. Interestingly, the materials like plastics, glass, cotton, stainless steel and fabrics showed the same level of inactivation. The study also highlighted that the size of the inoculum, degree of dilution of virus, and presence of any cellular debris also did not influence the anti-viral efficacies. In addition, the presence of human blood, tissues and corpses were also proven not to alter the degree of inactivation of viruses. This study also showed that when specific amounts of virus were sprayed in 2 chambers with and without ozone gas, 99% of viruses were inactivated in the chamber sprayed with ozone gas. They also highlighted that there was not even a single virus which was resistant to ozone. Finally, they also demonstrated the removal of ozone from the environment using a built-in catalytic converter equipped with the apparatus.

4.2. Ozone therapy as a novel treatment for “conventionally untreatable” viral illnesses

Rowen and Robins (2020) have proposed the use of ozone on treating the coronavirus in the context that the coronaviruses are abundance in cysteine, which must not be damaged for effective viral properties. However, the sulfhydryl functional groups are susceptible to oxidation and the O 3 therapy can make use of this vulnerability to deactivate the virus. They have highlighted that ozone therapy could assist the human system in deactivating the thiols in viruses in tissues and in blood by creating more oxidized environment. Notably, the spike protein of coronavirus is also abundance in tryptophan ( Broer et al., 2006 ), which is vulnerable to oxidation  ( Virender and Nigel, 2010 ) next to cysteine.

Further, in this report they have mentioned that how ozone was used to treat patients infected with Ebola epidemic (dated back in October 2014), where they employed the Directly Administered Oxygen/Ozone gas Intravenously (DIV) using ozone of concentrations of 30–55 mcg of ozone/cc in a quantity of 20 cc and administered it to 5 patients on board over few min and found that all the 5 patients survived the attack of the virus. They mentioned that the treatment required an ozone generator, which could be run on car battery, medical-grade compressed O 2 , a syringe (and butterfly-type needle for the DIV technique). However, this method was found to cause few side effects including transient chest tightness, cough and irritation of veins. Nevertheless this method carried negligible cost and produced low waste materials in comparison to the autohaemotherapy and could be effectively employed during epidemics.

4.3. A cohort study on ozone therapy for SARS-CoV-2 pneumonia patients

Hernandez et al. (2020) have conducted cohort study on 18 COVID-19 confirmed patients with severe pneumonia. The mean age of the patients was 68 years with SD of 15 years, and 72.2% (n = 13) of the patients were male. Out of 18 patients, the ozonated autohemotherapy was given to 9 patients (50%). In the study, they observed that in an unadjusted comparison, the ozonated autohemotherapy required significantly shorter time to achieve the clinical improvement with higher proportion of patients, who achieved clinical improvements in 14 days. Similarly, in risk adjusted studies, it required shorter mean time to achieve the clinical improvement ( Fig. 4 ).

Kaplan–Meier survival curves ( Hernandez et al., 2020 ).

Notably, the following were highlighted as limitations of this study; small sample size, wide adjusted estimates of 95% Cls, possibility of unmeasured residuals, requires external validity. On the other hand, the key strengths of the study were considered as its observations on the real world COVID-19 patients and the use of regression modeling for the primary clinical outcome and risk-adjustments​ analyses, where it is claimed to provide new data denoting to the effective contribution of ozonated-autohaemotherapy towards treating severe COVID-19 pneumonia.

4.4. Cytoprotective properties of ozone therapy in treating the COVID-19

The report by Martínez-Sánchez et al. (2020) highlights that the action mechanism of ozone involves the modulation of O 2 ∕ O 3 as the Keap1/Nrf2/ARE pathways and the reduction of IL-6 and IL-1. In such process, as the homeostasis of free radicals and antioxidant balance are associated with the O 2 ∕ O 3 modulation (typically known as the ozone therapy), it can induce the cytoprotective effect which can be effectively exploited to treat the clinical conditions caused by SARS-CoV/COVID-19 ( Fig. 5 (a)–(b)). It has also been highlighted that the underlying principles and action mechanisms of cytoprotective activity of ozone therapy have been demonstrated clinically with other viruses and therefore future clinical studies are highly needed to validate and establish the potential use of ozone therapy in treating COVID-19.

(a) Nrf2/IL-1 β as biomarkers of balance Nrf2/NF- κ B pathway activation after and before O 2 ∕ O 3 treatment [Control-healthy volunteers; EM-Multiple sclerosis; EM+O3-Multiple sclerosis treated with O 2 /O 3 ], (b) Rate of the fold change values of NF- κ B/Nrf2 as index of balance NF- κ B/Nrf2 pathway activation with and without O 2 ∕ O 3 treatment [Control-Cardiomyocytes culture; DoX-cells plus doxorubicin; DoX+3- cell treated with doxorubicin (100 nM) and ozone] ( Martínez-Sánchez et al., 2020 ).

4.5. Ozone therapy-major autohemotherapy (MAH): A preliminary evaluation

Study 1 Zheng et al. (2020) have demonstrated their experience in treating two patients confirmed with COVID-19 by ozone therapy called major autohemotherapy (MAH). In this treatment, the MAH was given to two patients (two males of 53 and 66 years old) once on a daily basis consequently for 7 days. In each turn, 100 mL of venous blood was taken and blended with ozone gas at 1:1 ratio of O 2 ∕ O 3 to blood volume, with the end-concentration of O 2 ∕ O 3 being 20 μ g/mL. Upon the MAH-treatment, their symptoms disappeared rapidly and started recovering. It was observed that as compared to the baseline chest-imaging, the subsequent serial CT-scans exhibited progressively absorbed bilateral lung lesions. Later, the patients were discharged after meeting the necessary various criteria. Further, no adverse effects associated with MAH-treatment were observed and reported. In addition to this, they also highlighted that these two results were compared with two other cases of similar age and illness without subjecting to MAH-treatment, where they realized that the patients without MAH required extended duration of viral disinfection and treatment. They concluded that the ozone therapy-MAH may be a promising modality in treating and limiting the COVID-19 infections and further clinical studies are needed to evaluate the parameters such as dosage, effectiveness and duration of treatment. Notably, this clinical study was later approved by the Clinical Research Ethics Committee of Renmin Hospital of Wuhan University (WDRY2020-K020).

Study 2: In a study conducted by  Franzini et al. (2020) 78 positive elderly patients were considered. Among them many were also suffering from ARDS and interstitial pneumonia. O 2 – O 3 treatment was given to all these patients and their lab parameters were drawn and subjected to analysis. It was observed that there was a major reduction in inflammation burst (CRP  ≤  30%, IL-6  ≤  25%), a reduction in D-dimer ( ≤ 35%) and an elevation in pulmonary function indicated by O 2 saturation% ≥ 10%, and PaO 2 /FiO 2 ≥ 6%. Ozone was delivered to these patients by withdrawing 200 ml of blood from patients, then they were collected in a CE certified SANO 3 bag, treated with 45  μ g/ml of O 2 – O 3 mixture and then introduced into patient’s blood. This autohaemotherapy reported 0.7 adverse events for every 100,000 treatments. The treatment lasted for 30 min and was also found to be cost-effective. This treatment lasted from 5–5 cycles with 100-200 ml of O 2 – O 3 once a day for 5 consecutive days (dosage: 45  μ g/ml). Reduction was observed in inflammatory parameters like pro-calcitonin, PCT and fasting glucose. The greatest variability was seen with respect to serum lactate (mean: −8.220% ± 39.91SD) and PaO2/FiO2 (mean: ＋13.812% ± 58.897SD). In the same study patients having aortic dissection were also studied, in whom an increase in PO 2 and SatO2 were observed with ozone concentrations of 40  μ g/ml, 80  μ g/ml and 160 μ g/ml and hence concluded that ozone does not harm erythrocytes ( Franzini et al., 2020 ).

4.6. Intravenous ozonated saline: A novel therapy for COVID-19

Among many adjunctive ozone therapies for COVID-19, one of the recognized mechanisms is to improve the oxygenation of blood/tissue to avert the failures in multi-organ due to hypoxia. In this direction, Thorp et al. (2020) have examined the effect of ozonated-saline, which administered intravenously, on the oxygenation in human body. The obtained results showed that the intravenously administered ozonated-saline improved the oxygenation of blood/tissues and extended the ability of person to stay in a hypoxic-environment.

4.7. Ozone as a non-drug therapy

Wang et al. (2020a) have proposed non-drug therapy based techniques using light, thermal and gas-phase sources to combat the coronaviruses. Their proposal includes the following three techniques; (i) A new ventilator based on thermal and micro ozone, (ii) A treatment cabin based on far-infrared (IR), thermal-oxygen, thermal-air and thermal-micro ozone and (iii) Cold plasma physical treatment based on the pulse plasma to produce micro ozone to be inhaled to kill the viruses. However, these treatment plans are still in infant state and they have to be optimized and tested before the human use. It has been highlighted that as compared with the drug-based therapies, these physical techniques are safer as they would not cause any side effects, user-friendly and cost-effective.

4.8. Ozone to combat COVID-19 in environment

Apart from the possible applications of ozone-based therapies to combat coronaviruses in human, ozone has also been demonstrated to combat the coronaviruses in the environment through the mechanisms such as face masks, Lee et al. (2020) hand sanitizers ( Anon, 2020 ) and disinfectants to inactivate the viruses in food industries ( Roberto et al., 2020 ).

Lee et al. (2020) have demonstrated the loss of infectivity of virus to the human cell line (MRC-5) when introduced to ozone gas even for a short-period of time (1 min). Notably, in this investigation the human-coronavirus (HCoV-229E) was used instead of SARS-CoV-2 and the O 3 gas was generated via a system called dielectric barrier-discharge plasma (BDP) generator. Interestingly, the study also demonstrated that there was no functional and structural decline occurred in the face-masks even after their exposure to O 3 gas for 5 min. in this mechanism, the augmentation of HCoV-229E-RNA, as observed through reverse-transcription polymerase chain reaction, indicated that the loss of viral activity by ozone could be primarily due to the damage of envelop-proteins or viral-envelopes ( Fig. 6 ).

Schematic-diagram describing the disinfection of a face mask contaminated by a coronavirus using ozone produced by a dielectric barrier discharge plasma generator ( Lee et al., 2020 ).

Very recently, Samir K. Pal and his group ( Anon, 2020 ) have developed a long lasting hand sanitizer called “nano-sanitizer” consisting of alcohol encapsulated by the ozone-impregnated​ peroxidized lipid layers. Apparently, the ozone-impregnated peroxidized lipid layer protects the alcohol molecules and keep them long lasting on the surface on which it is sprayed. This nano sanitizer overcomes the existing problems with typical hand sanitizers such as dehydration of skin owing to frequent-use and instant anti-microbial activity without any protective action. Thus, this nano sanitizer ensures the hygienic and convenient sanitization for durable period of time.

5. Challenges in ozone treatment

One of the major drawbacks is with respect to airway hyperactivity and inflammation, because ozone must never be inhaled. Ozone reacts with Polyunsaturated Fatty Acids (PUFA) found in lipids of alveolar lining layer as mentioned before to form Lipid Ozonation Products. In addition to this, ozone in presence of water forms hydrogen peroxide and many aldehydes. This results in activation of specific lipases like phospholipase A 2 /phospholipase C which produces arachidonic acid. Arachidonic acid finally produces prostaglandins, platelet activating factor via cyclooxygenases and lipoxygenases enzymes. This interaction of ozone with various biomolecules also releases 4-hydroxynonenal, lipoperoxyl radicals, malonylaldehyde, isoprastanes, and ozonide in addition to hydrogen peroxide, of which hydrogen peroxide and 4-hydroxynonenal are most toxic and activate signal transduction pathways like NF- κ β , NO-synthase, protein kinases to enhance the release of TNF α , IL-1, IL-8, IFN γ , and TGF β 1. This enhances the production of ROS and hypochlorous acid with high inflow of neutrophils and activated macrophages, thus creating a vicious cycle ( Elvis and Ekta, 2011 , Sagai and Bocci, 2011 ).

Ozone can also form 3 β -hydroxy-5-oxo-5,6-secocholestan-6-al which can cause pulmonary toxicity, Alzheimer’s disease and atherosclerosis. Furthermore, the excess peroxidation can alter the membrane permeability, where the loss of functional groups can inactivate enzymes causing cell injury and cell death. Ozone can combine with NO 2 to form photochemical smog, hence can damage lung alveoli. It has been stated that antioxidants vitamin C, E are both useful in nullifying the oxidant effect of ozone ( Elvis and Ekta, 2011 ). Hence the above mentioned reactions can be prevented when mixed with human blood since ozone equilibrates with extracellular and intraerythrocytic water and then to hemoglobin to get completely oxidized (pO 2 increases from 40 to 400 mmHg]. Hence it is proposed that the dosage of ozone must be 25% of potent antioxidant capacity of plasma ( Sagai and Bocci, 2011 ).

6. Conclusion

COVID-19 is an unprecedented pandemic situation in the world. In pursuit of various treatment modalities, the drug-based therapy is considered to be more effective in all levels. However, the non-drug based approaches such as ozone ( O 3 ) therapy could be useful in combating coronaviruses and other deadly viruses in human body as well as in environment ( Valdenassi et al., 2020 ). There are multiple mechanisms proposed for anti-viral properties of ozone, which include (i) veridical properties, (ii) inhibition of viral-replication, (iii) oxygenation of blood and tissues, (iv) inhibition of inflammatory mediators, (v) activation of immune defenses via endogenous antioxidant, (vi) up regulation of HO-1 in endothelial cells, (vii) resisting the formation of micro-thrombus, (viii) delivery of more oxygen to tissues by stimulating the 2–3 diphosphoglycerate, (ix) promoting of immune activity through nuclear-factor and (x) cytoprotective activity ( Rowen, 2019 , Toon, 2020 , Simonetti et al., 2019 , Kahle et al., 2015 ). The major drawback of this therapy is considered to be its dosage, which could turn adverse upon if an optimum dosage is not administered as required by the patient. The other targets for controlling the infection include (i) spike protein based vaccine, (ii) Inhibition of transmembrane protease serine 2 (TMPRSS2) activity, (iii) blocking ACE2 receptor, and (iv) delivering excessive soluble form of ACE2 all of which requires further investigation and research. Accordingly, the meticulous and comprehensive research along with extensive clinical trials, ozone therapy can be effectively deployed across the world, even to the people below poverty line. Ozone therapy can be brought forefront with technological developments in all levels and promising to treat coronavirus and other deadly viruses in the world ( Rubio-Romero et al., 2020 , Coccia, 2017 , Sterpetti, 2020 ).

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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After Robin Williams took his own life, news media covered the story in great detail, leading many to argue that such reporting violated the family’s privacy.

Responding to Child Migration

An influx of children migrants posed logistical and ethical dilemmas for U.S. authorities while intensifying ongoing debate about immigration.

Retracting Research: The Case of Chandok v. Klessig

A researcher makes the difficult decision to retract a published, peer-reviewed article after the original research results cannot be reproduced.

Sacking Social Media in College Sports

In the wake of questionable social media use by college athletes, the head coach at University of South Carolina bans his players from using Twitter.

Selling Enron

Following the deregulation of electricity markets in California, private energy company Enron profited greatly, but at a dire cost.

Snyder v. Phelps

Freedom of speech was put on trial in a case involving the Westboro Baptist Church and their protesting at the funeral of U.S. Marine Matthew Snyder.

Something Fishy at the Paralympics

Rampant cheating has plagued the Paralympics over the years, compromising the credibility and sportsmanship of Paralympian athletes.

Sports Blogs: The Wild West of Sports Journalism?

Deadspin pays an anonymous source for information related to NFL star Brett Favre, sparking debate over the ethics of “checkbook journalism.”

Stangl & the Holocaust

Franz Stangl was the most effective Nazi administrator in Poland, killing nearly one million Jews at Treblinka, but he claimed he was simply following orders.

Teaching Blackface: A Lesson on Stereotypes

A teacher was put on leave for showing a blackface video during a lesson on racial segregation, sparking discussion over how to teach about stereotypes.

The Astros’ Sign-Stealing Scandal

The Houston Astros rode a wave of success, culminating in a World Series win, but it all came crashing down when their sign-stealing scheme was revealed.

The Central Park Five

Despite the indisputable and overwhelming evidence of the innocence of the Central Park Five, some involved in the case refuse to believe it.

The CIA Leak

Legal and political fallout follows from the leak of classified information that led to the identification of CIA agent Valerie Plame.

The Collapse of Barings Bank

When faced with growing losses, investment banker Nick Leeson took big risks in an attempt to get out from under the losses. He lost.

The Costco Model

How can companies promote positive treatment of employees and benefit from leading with the best practices? Costco offers a model.

The FBI & Apple Security vs. Privacy

How can tech companies and government organizations strike a balance between maintaining national security and protecting user privacy?

The Miss Saigon Controversy

When a white actor was cast for the half-French, half-Vietnamese character in the Broadway production of Miss Saigon , debate ensued.

The Sandusky Scandal

Following the conviction of assistant coach Jerry Sandusky for sexual abuse, debate continues on how much university officials and head coach Joe Paterno knew of the crimes.

The Varsity Blues Scandal

A college admissions prep advisor told wealthy parents that while there were front doors into universities and back doors, he had created a side door that was worth exploring.

Providing radiation therapy to cancer patients, Therac-25 had malfunctions that resulted in 6 deaths. Who is accountable when technology causes harm?

Welfare Reform

The Welfare Reform Act changed how welfare operated, intensifying debate over the government’s role in supporting the poor through direct aid.

Wells Fargo and Moral Emotions

In a settlement with regulators, Wells Fargo Bank admitted that it had created as many as two million accounts for customers without their permission.

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HBS Case Selections

Innovation at Moog Inc.

• Brian J. Hall
• Ashley V. Whillans
• Davis Heniford
• Dominika Randle
• Caroline Witten

Innovation at Google Ads: The Sales Acceleration and Innovation Labs (SAIL) (A)

• Linda A. Hill
• Emily Tedards

Juan Valdez: Innovation in Caffeination

• Michael I. Norton
• Jeremy Dann

UGG Steps into the Metaverse

• Shunyuan Zhang
• Sharon Joseph
• Sunil Gupta
• Julia Kelley

Metaverse Wars

• David B. Yoffie
• Matt Higgins

Roblox: Virtual Commerce in the Metaverse

• Ayelet Israeli
• Nicole Tempest Keller

Timnit Gebru: "SILENCED No More" on AI Bias and The Harms of Large Language Models

• Tsedal Neeley
• Stefani Ruper

Hugging Face: Serving AI on a Platform

• Shane Greenstein
• Kerry Herman
• Sarah Gulick

SmartOne: Building an AI Data Business

• Karim R. Lakhani
• Pippa Tubman Armerding
• Gamze Yucaoglu
• Fares Khrais

Honeywell and the Great Recession (A)

• Sandra J. Sucher
• Susan Winterberg

Target: Responding to the Recession

• Ranjay Gulati
• Catherine Ross
• Richard S. Ruback
• Royce Yudkoff

Hometown Foods: Changing Price Amid Inflation

• Julian De Freitas
• Jeremy Yang
• Das Narayandas

Elon Musk's Big Bets

• Eric Baldwin

Elon Musk: Balancing Purpose and Risk

• Shikhar Ghosh
• Sarah Mehta

Tesla's CEO Compensation Plan

• Krishna G. Palepu
• John R. Wells
• Gabriel Ellsworth

China Rapid Finance: The Collapse of China's P2P Lending Industry

• William C. Kirby
• Bonnie Yining Cao
• John P. McHugh

Forbidden City: Launching a Craft Beer in China

• Christopher A. Bartlett
• Carole Carlson

Booking.com

• Stefan Thomke
• Daniela Beyersdorfer

Innovation at Uber: The Launch of Express POOL

• Chiara Farronato
• Alan MacCormack

Racial Discrimination on Airbnb (A)

• Michael Luca
• Scott Stern
• Hyunjin Kim

GitLab and the Future of All-Remote Work (A)

• Prithwiraj Choudhury
• Emma Salomon

TCS: From Physical Offices to Borderless Work

Creating a virtual internship at goldman sachs.

• Iavor Bojinov

Unilever's Response to the Future of Work

• William R. Kerr
• Emilie Billaud
• Mette Fuglsang Hjortshoej

AT&T, Retraining, and the Workforce of Tomorrow

• Joseph B. Fuller
• Carl Kreitzberg

Leading Change in Talent at L'Oreal

• Lakshmi Ramarajan
• Vincent Dessain
• Emer Moloney
• William W. George
• Andrew N. McLean

Eve Hall: The African American Investment Fund in Milwaukee

• Steven S. Rogers
• Alterrell Mills

United Housing - Otis Gates

• Mercer Cook

The Home Depot: Leadership in Crisis Management

• Herman B. Leonard
• Marc J. Epstein
• Melissa Tritter

The Great East Japan Earthquake (B): Fast Retailing Group's Response

• Hirotaka Takeuchi
• Kenichi Nonomura
• Dena Neuenschwander
• Meghan Ricci
• Kate Schoch
• Sergey Vartanov

Insurer of Last Resort?: The Federal Financial Response to September 11

• David A. Moss
• Sarah Brennan

Under Armour

• Rory McDonald
• Clayton M. Christensen
• Daniel West
• Jonathan E. Palmer
• Tonia Junker

Hunley, Inc.: Casting for Growth

• John A. Quelch
• James T. Kindley

Bitfury: Blockchain for Government

• Mitchell B. Weiss
• Elena Corsi

Deutsche Bank: Pursuing Blockchain Opportunities (A)

• Lynda M. Applegate
• Christoph Muller-Bloch

Maersk: Betting on Blockchain

• Scott Johnson

Yum! Brands

• Jordan Siegel
• Christopher Poliquin

Bharti Airtel in Africa

• Tanya Bijlani

Li & Fung 2012

• F. Warren McFarlan
• Michael Shih-ta Chen
• Keith Chi-ho Wong

Sony and the JK Wedding Dance

• John Deighton
• Leora Kornfeld

United Breaks Guitars

David dao on united airlines.

• Benjamin Edelman
• Jenny Sanford

Marketing Reading: Digital Marketing

• Joseph Davin

Social Strategy at Nike

• Mikolaj Jan Piskorski
• Ryan Johnson

The Tate's Digital Transformation

Social strategy at american express, mellon financial and the bank of new york.

• Carliss Y. Baldwin
• Ryan D. Taliaferro

The Walt Disney Company and Pixar, Inc.: To Acquire or Not to Acquire?

• Juan Alcacer
• David J. Collis

Dow's Bid for Rohm and Haas

• Benjamin C. Esty

Finance Reading: The Mergers and Acquisitions Process

• John Coates

Apple: Privacy vs. Safety? (A)

• Henry W. McGee
• Nien-he Hsieh
• Sarah McAra

Sidewalk Labs: Privacy in a City Built from the Internet Up

• Leslie K. John

Data Breach at Equifax

• Suraj Srinivasan
• Quinn Pitcher
• Jonah S. Goldberg

Apple's Core

• Noam Wasserman

Design Thinking and Innovation at Apple

• Barbara Feinberg

Apple Inc. in 2012

• Penelope Rossano

Iz-Lynn Chan at Far East Organization (Abridged)

• Anthony J. Mayo
• Dana M. Teppert

Barbara Norris: Leading Change in the General Surgery Unit

• Boris Groysberg
• Nitin Nohria
• Deborah Bell

Adobe Systems: Working Towards a "Suite" Release (A)

• David A. Thomas
• Lauren Barley
• Jan W. Rivkin

Starbucks Coffee Company: Transformation and Renewal

• Nancy F. Koehn
• Kelly McNamara
• Nora N. Khan
• Elizabeth Legris

JCPenney: Back in Business

• K. Shelette Stewart
• Christine Snively

Home Nursing of North Carolina

Castronics, llc, gemini investors, angie's list: ratings pioneer turns 20.

• Robert J. Dolan

Basecamp: Pricing

• Frank V. Cespedes
• Robb Fitzsimmons

J.C. Penney's "Fair and Square" Pricing Strategy

J.c. penney's 'fair and square' strategy (c): back to the future.

• Jose B. Alvarez

Osaro: Picking the best path

• James Palano
• Bastiane Huang

HubSpot and Motion AI: Chatbot-Enabled CRM

• Thomas Steenburgh

GROW: Using Artificial Intelligence to Screen Human Intelligence

• Ethan S. Bernstein
• Paul D. McKinnon
• Paul Yarabe

Arup: Building the Water Cube

• Robert G. Eccles
• Amy C. Edmondson
• Dilyana Karadzhova

(Re)Building a Global Team: Tariq Khan at Tek

Managing a global team: greg james at sun microsystems, inc. (a).

• Thomas J. DeLong

Organizational Behavior Reading: Leading Global Teams

Ron ventura at mitchell memorial hospital.

• Heide Abelli

Anthony Starks at InSiL Therapeutics (A)

• Gary P. Pisano
• Vicki L. Sato

Wolfgang Keller at Konigsbrau-TAK (A)

• John J. Gabarro

The 2010 Chilean Mining Rescue (A)

• Faaiza Rashid

IDEO: Human-Centered Service Design

• Ryan W. Buell
• Andrew Otazo
• Benjamin Jones
• Alexis Brownell

David Neeleman: Flight Path of a Servant Leader (A)

• Matthew D. Breitfelder

Coach Hurley at St. Anthony High School

• Scott A. Snook
• Bradley C. Lawrence

Shapiro Global

• Michael Brookshire
• Monica Haugen
• Michelle Kravetz
• Sarah Sommer

Kathryn McNeil (A)

• Joseph L. Badaracco Jr.
• Jerry Useem

Carol Fishman Cohen: Professional Career Reentry (A)

• Myra M. Hart
• Robin J. Ely
• Susan Wojewoda

Alex Montana at ESH Manufacturing Co.

• Michael Kernish

Michelle Levene (A)

• Tiziana Casciaro
• Victoria W. Winston

John and Andrea Rice: Entrepreneurship and Life

• Howard H. Stevenson
• Janet Kraus
• Shirley M. Spence

Partner Center

2020 DPDx Case Studies

2020 | 2019 | 2018 | 2017 | 2016 | 2015 | 2014 | 2013 | 2012 | 2011 | 2010 | 2009 | 2008 | 2007 | 2006 | 2005

56-year-old Korean immigrant sought medical attention for non-specific abdominal pain and mild, intermittent diarrhea.

A 42-year-old State Park employee sought medical care due to fatigue, insomnia, intermittent bloating, and mild anemia.

A 45-year-old male who recently returned from a trip overseas to Korea presented to his primary care clinic for an annual checkup at a clinic in the United States.

During a field study in Cambodia, stool ova and parasite (O&P) examinations were performed on participants in rural villages. Unusual eggs were found in the formalin-ethyl acetate concentrated stool specimen of one middle-aged woman.

A 53-year-old woman from Florida presented to a dermatology clinic with a raised, itchy, red rash on her torso that persisted over the past six months and did not respond to topical treatments.

A 25-year-old man with fever and myalgia presented to an urgent care clinic in Pennsylvania, and no travel history was obtained at that time.

As part of a refugee screening program, a young child had a fecal ova and parasite (O & P) examination which included a formalin-ethyl acetate (FEA) fecal concentration.

At a regional diagnostic laboratory, where specimens from the southeastern United States are evaluated, the objects shown in Figures A and B were observed on a wet mount preparation from a fecal formalin-ethyl acetate (FEA) concentrate.

In Singapore, a 54-year-old man with an extensive travel history to Vietnam, Thailand, and France presented to a clinic with prolonged fever, urticarial rash, and muscle aches.

A 67-year-old male from Houston, TX sought medical evaluation following 3 days of abdominal pain, diarrhea, and fatigue after returning from a two-week summer vacation in Nairobi, Kenya.

An 18-year-old male living in India presented with recurrent periumbilical abdominal pain for one week. Other symptoms included mild anemia and eosinophilic leukocytosis.

A 24-year-old man from Thailand presented to his healthcare provider with complaints of gastrointestinal pain and weight loss. He also reported seeing thin worms in his stool on rare occasion.

A group of college students traveled to Brazil on a rafting and camping trip for two weeks. Malaria prophylaxis was highly recommended however one student declined.

A 58 year-old-man from Peru visiting relatives in the United States was killed in a traffic accident. An autopsy revealed cysts in his liver of which a few were excised and sent to pathology for identification.

A 4-year-old boy went for a routine medical examination with his parents after they returned from a one-year sabbatical, studying primates in their natural habitat in central Africa.

A 24-year-old female exchange student from Guinea reported to the clinic with headaches, itchy skin, and enlarged lymph nodes.

A 60-year-old non-smoking male patient presented to his primary care physician with a chronic cough and shortness of breath. He reported no recent travel outside of the Southern United States.

A 29-year-old female patient presented to her primary care physician reporting a 15-day history of whitish, vaginal discharge associated with itching.

A 3-year-old boy was seen by a pediatrician for gastrointestinal pain and watery diarrhea. His parents conveyed that he has a propensity for putting insects in his mouth and sometimes eating them.

A 29-year-old man sought medical attention with his health care provider with a complaint of itchy maculopapular rash on several areas of his body.

A 63-year-old man returned from visiting with family in Nigeria. He developed fever, chills and a mild headache three days before presenting to the clinic.

A 69-year-old male patient from a rural town in Georgia experiencing symptoms of productive cough with blood, hematochezia (rectal bleeding) and chest pain sought medical attention at the county health clinic.

DPDx is an educational resource designed for health professionals and laboratory scientists. For an overview including prevention, control, and treatment visit www.cdc.gov/parasites/ .

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Top 40 Most Popular Case Studies of 2018

Cases about food and agriculture took center stage in 2018. A case on the coffee supply chain remained the top case and cases on burgers, chocolate, and palm oil all made the top ten.

Cases about food and agriculture took center stage in 2018. A case on the coffee supply chain remained the top case and cases on burgers, chocolate, and palm oil all made the top ten, according to data compiled by Yale School of Management Case Research and Development Team (SOM CRDT).

Other topics in the top ten included corporate social responsibility, healthcare, solar energy, and financial inclusion.

The annual ranking of the 40 most popular Yale School of Management case studies combines data from publishers, Google analytics, SOM class syllabi, and other measures of interest and adoption. This is the second year that SOM CRDT has published its Top 40 list.

Cases published in 2018 on the top 40 list included Marina Bay Sands Hotel (#13), AgBiome (#18), Canary Wharf (#20), Mastercard (#21), and Peabody Museum (#35). Both the Marina Bay Sands and Peabody cases were featured in major student competitions in 2018.

The cases on the Top 40 list represent a variety of different business disciplines, as Yale SOM cases tend to combine a variety of perspectives. For example, the top coffee case can be taught in marketing, operations, and strategy classes. The number two case on Shake Shack covers finance, strategy, and even innovation and design. The list features a number of cases related to the interplay of state and commerce and social enterprise, traditional strengths of the Yale SOM curriculum.

While there are many US-based cases among the top 40, a range of locales are highlighted among the top 40 entries. Cases set in France (AXA), Great Britain (Cadbury, Canary Wharf, George Hudson), Indonesia (Palm Oil, Golden Agri), China (Ant Financial, Alibaba), India (SELCO, Project Sammaan), Singapore (Marina Bay Sands), Canada (Air Canada, Potash Corporation of Saskatchewan), and South Africa (Project Masiluleke) made the top 40 list.

SOM CRDT has been working to increase the number of women featured as case protagonists. The 2018 list boasts 13 cases where women play prominent roles in the narrative.

The top 40 list also demonstrates a wide range of SOM faculty involvement. Thirty different faculty members worked as case supervisors on the top 40 cases.

Read on to learn more about the top 10 most popular cases followed by a complete list of the top 40 cases of 2018. A selection of the top 40 cases are available for purchase through our online store . 

#1 - Coffee 2016

Faculty Supervision: Todd Cort

Coffee 2016 asks students to consider the coffee supply chain and generate ideas for what can be done to equalize returns across various stakeholders. The case draws a parallel between coffee and wine. Both beverages encourage connoisseurship, but only wine growers reap a premium for their efforts to ensure quality.  The case describes the history of coffee production across the world, the rise of the “third wave” of coffee consumption in the developed world, the efforts of the Illy Company to help coffee growers, and the differences between “fair” trade and direct trade. Faculty have found the case provides a wide canvas to discuss supply chain issues, examine marketing practices, and encourage creative solutions to business problems. 

#2 - Shake Shack IPO

Faculty Supervision: Jake Thomas and Geert Rouwenhorst

From an art project in a New York City park, Shake Shack developed a devoted fan base that greeted new Shake Shack locations with cheers and long lines. When Shake Shack went public on January 30, 2015, investors displayed a similar enthusiasm. Opening day investors bid up the $21 per share offering price by 118% to reach $45.90 at closing bell. By the end of May, investors were paying $92.86 per share. Students are asked if this price represented a realistic valuation of the enterprise and if not, what was Shake Shack truly worth? The case provides extensive information on Shake Shack’s marketing, competitors, operations and financials, allowing instructors to weave a wide variety of factors into a valuation of the company.

#3 - IBM Corporate Service Corps

Faculty Supervision: David Bach in cooperation with University of Ghana Business School and EGADE

The case considers IBM’s Corporate Service Corps (CSC), a program that had become the largest pro bono consulting program in the world. The case describes the program’s triple-benefit: leadership training to the brightest young IBMers, brand recognition for IBM in emerging markets, and community improvement in the areas served by IBM’s host organizations. As the program entered its second decade in 2016, students are asked to consider how the program can be improved. The case allows faculty to lead a discussion about training, marketing in emerging economies, and various ways of providing social benefit. The case highlights the synergies as well as trade-offs between pursuing these triple benefits.

#4 - Children’s Premier

Faculty Supervision: Edieal Pinker

The case describes Children’s Premier, a popular group practice in Greenwich, Connecticut which, due to a change in the state’s vaccination law, decides to dramatically change its business model. Did the group make the right adjustments in order to stay competitive and cover their increasing costs? Should the new practices cause a newcomer to the practice to look elsewhere for his children?

#5 - Design at Mayo

Faculty Supervision: Rodrigo Canales and William Drentell

The case describes how the Mayo Clinic, one of the most prominent hospitals in the world, engaged designers and built a research institute, the Center for Innovation (CFI), to study the processes of healthcare provision. The case documents the many incremental innovations the designers were able to implement and the way designers learned to interact with physicians and vice-versa.

In 2010 there were questions about how the CFI would achieve its stated aspiration of “transformational change” in the healthcare field. Students are asked what would a major change in health care delivery look like? How should the CFI's impact be measured? Were the center's structure and processes appropriate for transformational change? Faculty have found this a great case to discuss institutional obstacles to innovation, the importance of culture in organizational change efforts, and the differences in types of innovation.

This case is freely available to the public.

#6 - AXA: Creating New Corporate Responsibility Metrics

Faculty Supervision: Todd Cort and David Bach

The case describes AXA’s corporate responsibility (CR) function. The company, a global leader in insurance and asset management, had distinguished itself in CR since formally establishing a CR unit in 2008. As the case opens, AXA’s CR unit is being moved from the marketing function to the strategy group occasioning a thorough review as to how CR should fit into AXA’s operations and strategy. Students are asked to identify CR issues of particular concern to the company, examine how addressing these issues would add value to the company, and then create metrics that would capture a business unit’s success or failure in addressing the concerns.

#7 - Cadbury: An Ethical Company Struggles to Insure the Integrity of Its Supply Chain

Faculty Supervision: Ira Millstein

The case describes revelations that the production of cocoa in the Côte d’Ivoire involved child slave labor. These stories hit Cadbury especially hard. Cadbury's culture had been deeply rooted in the religious traditions of the company's founders, and the organization had paid close attention to the welfare of its workers and its sourcing practices. The US Congress was considering legislation that would allow chocolate grown on certified plantations to be labeled “slave labor free,” painting the rest of the industry in a bad light. Chocolate producers had asked for time to rectify the situation, but the extension they negotiated was running out. Students are asked whether Cadbury should join with the industry to lobby for more time?  What else could Cadbury do to ensure its supply chain was ethically managed?

#8 - Palm Oil 2016

Faculty Supervision: Kenneth Richards in cooperation with National University of Singapore Business School and David Bach

The case looks at the palm oil industry in Indonesia and how the industry effects deforestation and native rights. The case focuses on a proposal forwarded by leading palm oil traders and environmental NGOs that would ban the sale of palm oil from deforested land. The proposal is opposed by elements of the government, and smaller palm oil companies. Some voices in the Indonesian government are suggesting an agreement to end deforestation needs to be scrapped. What should companies and NGOs do?

#9 - Ant Financial

Faculty Supervision: K. Sudhir in cooperation with Renmin University of China School of Business

In 2015, Ant Financial’s MYbank (an offshoot of Jack Ma’s Alibaba company) was looking to extend services to rural areas in China by providing small loans to farmers. Microloans have always been costly for financial institutions to offer to the unbanked (though important in development) but MYbank believed that fintech innovations such as using the internet to communicate with loan applicants and judge their credit worthiness would make the program sustainable. Students are asked whether MYbank could operate the program at scale? Would its big data and technical analysis provide an accurate measure of credit risk for loans to small customers? Could MYbank rely on its new credit-scoring system to reduce operating costs to make the program sustainable?

#10 - SELCO

Faculty Supervision: Tony Sheldon

The case looks at SELCO, an Indian company that specialized in bringing solar electric products to the poor. In 2009, the company needed a new growth strategy. As students consider the company’s dilemma, the raw case allows them to view video interviews with company leaders and customers, inspect maps of SELCO’s service areas, see videos describing how SELCO’s products were being used, consider articles on India’s electricity grid and socio-economic conditions, read about the company’s founding, consult the company’s organization charts, income statements and balance sheets, inspect the company’s innovative products, review the company’s business models, read news articles about the company’s success, etc.

SELCO, India's innovative solar electric company, was at a strategic crossroads. Should it go “deeper” and serve even poorer people or go “wider” and expand beyond its current geographical areas?

40 Most Popular Case Studies of 2018

Click on the case title to learn more about the dilemma. A selection of our most popular cases are available for purchase via our online store .

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Detectives Just Used DNA To Solve A 1956 Double Homicide. They May Have Made History

Sharon Pruitt-Young

Clippings from the Great Falls Tribune were part of the Cascade County Sheriff's Office investigative file into the 1956 murders of Patricia Kalitzke and Lloyd Duane Bogle. Traci Rosenbaum/USA Today Network via Reuters Co. hide caption

Clippings from the Great Falls Tribune were part of the Cascade County Sheriff's Office investigative file into the 1956 murders of Patricia Kalitzke and Lloyd Duane Bogle.

It was only three days into 1956 when three boys from Montana, out for a hike on a normal January day, made a gruesome discovery they were unlikely to ever forget.

During a walk near the Sun River, they found 18-year-old Lloyd Duane Bogle, dead from a gunshot wound to the head. They found him on the ground near his car, and someone had used his belt to tie his hands behind his back, according to a report from the Great Falls Tribune . The next day brought another disturbing discovery: A county road worker found 16-year-old Patricia Kalitzke's body in an area north of Great Falls, the paper reports. She had been shot in the head, just as Bogle had been, but she had also been sexually assaulted.

Their killings went unsolved until this week when investigators announced they had cracked what is believed to be the oldest case solved with DNA and forensic genealogy.

The victims were discovered in a lover's lane

Bogle, an airman hailing from Texas, and Kalitzke, a junior at Great Falls High School, had fallen for each other and were even considering marriage, the Tribune reports. The place where they were believed to have been killed was a known "lover's lane," according to a clipping from a local newspaper posted on a memorial page.

But their love story was brutally cut short by the actions of a killer whose identity would not be revealed for more than 60 years. And it was not for lack of trying: Early on in the case, investigators followed numerous leads, but none of them panned out. The case eventually went cold.

For decades, the Cascade County Sheriff's Office continued to work on it, with multiple detectives attempting to make progress over the years. One such investigator was Detective Sgt. Jon Kadner, who was assigned the case in 2012 — his first cold case, he said during an interview with NPR. He was immediately met with the daunting task of digitizing the expansive case file, an endeavor that took months.

He continued to work on the Kalitzke/Bogle case even while handling the newer cases that were landing on his desk all the time, but he had a feeling that more was needed to get to the bottom of what had happened to the couple all those decades ago.

"My first impression was that the only way we're gonna ever solve this is through the use of DNA," Kadner said.

Detectives turned to a new forensic investigation

Fortunately, Kadner had something to work with. During Kalitzke's autopsy in 1956, coroners had taken a vaginal swab, which had been preserved on a microscopic slide in the years since, according to the Great Falls Tribune report. Phil Matteson, a now-retired detective with the sheriff's office, sent that sample to a local lab for testing in 2001, and the team there identified sperm that did not belong to Bogle, her boyfriend, the paper reports.

Armed with this knowledge, Kadner in 2019 sought out the assistance of Bode Technology. After forensic genealogy was used to finally nab the Golden State Killer the year prior, law enforcement officials were becoming increasingly aware of the potential to use that technology to solve cold cases — even decades-old cases like Kalitzke and Bogle's.

With the help of partnering labs, forensic genealogists are able to use preserved samples to create a DNA profile of the culprit and then use that profile to search public databases for any potential matches. In most cases, those profiles can end up linking to distant relatives of the culprit — say, a second or third cousin. By searching public records (such as death certificates and newspaper clippings), forensic genealogists are then able to construct a family tree that can point them right to the suspect, even if that suspect has never provided their DNA to any public database.

In this case, "Our genealogists, what they're going to do is independently build a family tree from this cousin's profile," Andrew Singer, an executive with Bode Technology, told NPR. He called it "a reverse family tree. ... We're essentially going backwards. We're starting with a distant relative and trying to work back toward our unknown sample."

It worked: DNA testing led investigators to a man named Kenneth Gould. Before moving to Missouri in 1967, Gould had lived with his wife and children in the Great Falls area around the time of the murders, according to the Tribune .

"It felt great because for the first time in 65 years we finally had a direction and a place to take the investigation," Kadner told NPR. "Because it was all theories up to that point ... we finally had a match and we had a name. That changed the whole dynamic of the case."

Investigators' goal is a safer world

But there was one big problem: Gould had died in 2007 and his remains had been cremated, according to the Tribune . The only way to prove his guilt or his innocence was to test the DNA of his remaining relatives.

Detectives had an uncomfortable task ahead of them: letting a dead man's family know that, despite the fact that he'd never previously been identified as a person of interest, he was now the key suspect in a double homicide and rape.

Authorities traveled to Missouri, where they spoke with Gould's children and told them about the Kalitzke/Bogle case and eventually identified their father as a suspect, Kadner said. They asked for the family's help in either proving or disproving that Gould was the man responsible and the family complied.

The test results said Gould was the guy. With the killer finally identified, Kadner was able to reach out to the victims' surviving relatives and deliver the closure that had taken more than 60 years to procure. It was a bittersweet revelation: They were grateful for answers, but for many of the older people in the family, it was a struggle to have those wounds reopened.

"They're excited, but at the same time, it has brought up a lot of memories," Kadner said.

Now, the sheriff's office is considering forming a cold case task force, as other law enforcement agencies have done. The hope is that they'll be able to provide more families with the answers they deserve and, in many cases, have spent years waiting for.

"If there's new technology and we are able to potentially solve something, we want to keep working at it, because ultimately we're trying to do it for the family," he said. "Give them some closure."

The Kalitzke/Bogle case is one of the oldest criminal cases that has been solved using forensic genealogy, and authorities are hopeful that they'll be able to use this ever-advancing technology to solve cold cases dating back even further — although new state legislation restricting forensic genealogy could complicate matters.

Even without that complication, Singer explained to NPR, the success rate depends heavily on how well the evidence has been preserved over the years. Still, he hopes that it can be used to help law enforcement improve public safety and "[prevent] tomorrow's victim."

"It's really fantastic technology and it's going to solve a lot of cold cases," Singer said.

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Methodology

• What Is a Case Study? | Definition, Examples & Methods

What Is a Case Study? | Definition, Examples & Methods

Published on May 8, 2019 by Shona McCombes . Revised on June 22, 2023.

A case study is a detailed study of a specific subject, such as a person, group, place, event, organization, or phenomenon. Case studies are commonly used in social, educational, clinical, and business research.

A case study research design usually involves qualitative methods , but quantitative methods are sometimes also used. Case studies are good for describing , comparing, evaluating and understanding different aspects of a research problem .

Table of contents

When to do a case study, step 1: select a case, step 2: build a theoretical framework, step 3: collect your data, step 4: describe and analyze the case, other interesting articles.

A case study is an appropriate research design when you want to gain concrete, contextual, in-depth knowledge about a specific real-world subject. It allows you to explore the key characteristics, meanings, and implications of the case.

Case studies are often a good choice in a thesis or dissertation . They keep your project focused and manageable when you don’t have the time or resources to do large-scale research.

You might use just one complex case study where you explore a single subject in depth, or conduct multiple case studies to compare and illuminate different aspects of your research problem.

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Once you have developed your problem statement and research questions , you should be ready to choose the specific case that you want to focus on. A good case study should have the potential to:

• Provide new or unexpected insights into the subject
• Challenge or complicate existing assumptions and theories
• Propose practical courses of action to resolve a problem
• Open up new directions for future research

TipIf your research is more practical in nature and aims to simultaneously investigate an issue as you solve it, consider conducting action research instead.

Unlike quantitative or experimental research , a strong case study does not require a random or representative sample. In fact, case studies often deliberately focus on unusual, neglected, or outlying cases which may shed new light on the research problem.

Example of an outlying case studyIn the 1960s the town of Roseto, Pennsylvania was discovered to have extremely low rates of heart disease compared to the US average. It became an important case study for understanding previously neglected causes of heart disease.

However, you can also choose a more common or representative case to exemplify a particular category, experience or phenomenon.

Example of a representative case studyIn the 1920s, two sociologists used Muncie, Indiana as a case study of a typical American city that supposedly exemplified the changing culture of the US at the time.

While case studies focus more on concrete details than general theories, they should usually have some connection with theory in the field. This way the case study is not just an isolated description, but is integrated into existing knowledge about the topic. It might aim to:

• Exemplify a theory by showing how it explains the case under investigation
• Expand on a theory by uncovering new concepts and ideas that need to be incorporated
• Challenge a theory by exploring an outlier case that doesn’t fit with established assumptions

To ensure that your analysis of the case has a solid academic grounding, you should conduct a literature review of sources related to the topic and develop a theoretical framework . This means identifying key concepts and theories to guide your analysis and interpretation.

There are many different research methods you can use to collect data on your subject. Case studies tend to focus on qualitative data using methods such as interviews , observations , and analysis of primary and secondary sources (e.g., newspaper articles, photographs, official records). Sometimes a case study will also collect quantitative data.

Example of a mixed methods case studyFor a case study of a wind farm development in a rural area, you could collect quantitative data on employment rates and business revenue, collect qualitative data on local people’s perceptions and experiences, and analyze local and national media coverage of the development.

The aim is to gain as thorough an understanding as possible of the case and its context.

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In writing up the case study, you need to bring together all the relevant aspects to give as complete a picture as possible of the subject.

How you report your findings depends on the type of research you are doing. Some case studies are structured like a standard scientific paper or thesis , with separate sections or chapters for the methods , results and discussion .

Others are written in a more narrative style, aiming to explore the case from various angles and analyze its meanings and implications (for example, by using textual analysis or discourse analysis ).

In all cases, though, make sure to give contextual details about the case, connect it back to the literature and theory, and discuss how it fits into wider patterns or debates.

If you want to know more about statistics , methodology , or research bias , make sure to check out some of our other articles with explanations and examples.

• Normal distribution
• Degrees of freedom
• Null hypothesis
• Discourse analysis
• Control groups
• Mixed methods research
• Non-probability sampling
• Quantitative research
• Ecological validity

Research bias

• Rosenthal effect
• Implicit bias
• Cognitive bias
• Selection bias
• Negativity bias
• Status quo bias

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Impact of livestock industry on climate change : Case Study in South Korea

Affiliations.

• 1 Department of Animal Science and Technology, Chung-Ang University, Anseong 17546, Korea.
• 2 Farm and Table Co. Ltd., Seoul 06339, Korea.
• 3 Department of Agricultural Biotechnology, Center for Food and Bioconvergence, and Research Institute of Agriculture and Life Science, Seoul National University, Seoul 08826, Korea.
• 4 Department of Food and Nutrition, Sookmyung Women's University, Seoul 04310, Korea.
• 5 Department of Animal Science and Technology, Sunchon National University, Suncheon 57922, Korea.
• PMID: 37946432
• DOI: 10.5713/ab.23.0256

In recent years, there has been a growing argument attributing the primary cause of global climate change to livestock industry, which has led to the perception that the livestock industry is synonymous with greenhouse gas (GHG) emissions. However, a closer examination of the global GHG emission by sector reveals that the energy sector responsible for the majority, accounting for 76.2% of the total, while agriculture contributes 11.9%. According to data from the Food and Agriculture Organization of the United Nations (FAO), the total GHG emissions associate with the livestock supply chain amount to 14.5%. Within this, emissions from direct sources, such as enteric fermentation and livestock manure treatment, which are not part of the front and rear industries, represent only 7%. Although it is true that the increase in meat consumption driven by global population growth and rising incomes, has contributed to higher methane (CH4) emissions resulting from enteric fermentation in ruminant animals, categorizing the livestock industry as the primary source of GHG emissions oversimplifies a complex issue and disregards objective data. Therefore, it may be a misleading to solely focus on the livestock sector without addressing the significant emissions from the energy sector, which is the largest contributor to GHG emissions. The top priority should be the objective and accurate measurement of GHG emissions, followed by the development and implementation of suitable reduction policies for each industrial sector with significant GHG emissions contributions.

Keywords: Carbon Footprint; Climate Change; Environment; Greenhouse Gases; Livestock Industry.

A blockbuster gun rights case lands at the Supreme Court. Here are three justices to watch.

The controversial case tests the limits of a blockbuster second amendment decision that requires gun prohibitions to be grounded in the nation's history..

WASHINGTON − With the nation reeling from the deadliest mass shooting of the year , the Supreme Court this week will hash out a Second Amendment dispute that could have enormous consequences for victims of domestic violence .

On Tuesday, the court will hear oral arguments about a law banning people who are subject to a domestic violence restraining order from owning a gun. Studies indicate that women are five times more likely to die from domestic violence if a gun is present.

The case centers on a Texas man involved in five shootings between 2020 and 2021 who pleaded guilty to a federal crime: possessing a firearm despite being the subject of a domestic violence restraining order. His appeal to the Supreme Court could have sweeping implications for other gun prohibitions.

That's because his attorneys are relying on a blockbuster Supreme Court decision from just over a year ago to challenge the constitutionality of the federal law he was charged with violating. In that case, the court ruled that gun regulations must be "consistent with this nation's historical tradition of firearm regulation" to survive court challenges. Justice Stephen Breyer, who has since retired, noted a study in his dissent about the increased risk for domestic violence victims when guns are present.

"It's common sense: Domestic abusers should not have guns," said Esta Soler, president of Futures without Violence, a group that advocates for ending domestic violence. "When guns and domestic violence mix, women and children die."

LGBTQ rights: Legal fight over gender-affirming care reaches the Supreme Court. Here's what's next.

The Supreme Court will hear arguments in the case, U.S. v. Rahimi, at 10 a.m. EST Tuesday.

Here are three justices to watch − and why − when those arguments get underway.

Kavanaugh: No 'blank check' on guns

Justice Brett Kavanaugh and Chief Justice John Roberts are always important to watch because they sit at the ideological center of the court and can swing the outcome of a case one way or the other .

That could be particularly true on guns. While both conservatives voted to knock down the New York gun licensing law at issue in Bruen , they also both signed onto a concurring opinion that spelled out some limits to that decision. Kavanaugh stressed that the court's landmark decision last year should not be read to cast doubt on prohibitions on the "possession of firearms by felons and the mentally ill."

States, Kavanaugh wrote, could still mandate licenses for gun purchases, requiring people to be fingerprinted and submit to background checks, training and mental health records checks.

Domestic violence wasn't raised in the court's opinion nor Kavanaugh's concurring opinion. Breyer noted the study in his dissent in last year's gun ruling that found a woman is five times more likely to be killed by a partner if he has access to a gun. Justice Samuel Alito asked in a concurring opinion why that was relevant to the questions resolved in Bruen.

Barrett: 'Dangerous people'

Justice Amy Coney Barrett will be important to watch because she addressed similar questions four years ago as an appeals court judge in Chicago. Barrett's position there could give the conservatives a way to rule against Rahimi while still honoring the precedent they set down last year.

"History is consistent with common sense," Barrett wrote in a dissenting opinion in 2019 . "It demonstrates that legislatures have the power to prohibit dangerous people from possessing guns."

The 7th U.S. Circuit Court of Appeals case dealt with a Wisconsin man barred from owning a gun because he was convicted of felony mail fraud in a scheme to defraud Medicare. In a 2-1 decision, the appeals court upheld laws that barred the man from owning a gun because of his conviction. Barrett dissented, writing that people can't be denied rights just because they are felons but that people deemed dangerous might be out of luck.

Eighteen months after Barrett's opinion appeared, President Donald Trump nominated her to the Supreme Court .

Thomas: In search of 'original meaning'

Justice Clarence Thomas is often considered the Supreme Court's foremost proponent of originalism , the practice of interpreting the words of the Constitution as they would have been understood by the framers at the time of the nation's founding. It was Thomas who wrote the majority opinion in Bruen , holding that gun restrictions must be "consistent with  this nation's historical tradition of firearm regulation " in order to survive a legal challenge.

Thomas, who almost always asks the first question in arguments these days, will be closely watched for any sign of attempting to square his originalist ideology with the government's defense of the law on restraining orders.

Critics say the Rahimi case pokes a hole in the wisdom of attempting to understand what the framers had in mind when the Second Amendment was adopted in 1791. Back then, after all, women had fewer legal rights and guns were rarely used in domestic disputes, according to a brief in the case filed by 18 legal historians.

"If domestic violence in the eighteenth century had been strongly linked to firearms, such violence could have and almost certainly would have been regulated as a threat to the public peace," the historians told the court this year.

Related: Guns in America: Supreme Court agrees to hear challenge to Trump-era ban on bump stocks

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• 07 November 2023

Nature retracts controversial superconductivity paper by embattled physicist

• Davide Castelvecchi

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Physicist Ranga Dias is under investigation by his institution, the University of Rochester in New York. Credit: Lauren Petracca/New York Times/Redux/eyevine

Nature has retracted a controversial paper 1 claiming the discovery of a superconductor — a material that carries electrical currents with zero resistance — capable of operating at room temperature and relatively low pressure.

Why a blockbuster superconductivity claim met a wall of scepticism

The text of the retraction notice states that it was requested by eight co-authors. “They have expressed the view as researchers who contributed to the work that the published paper does not accurately reflect the provenance of the investigated materials, the experimental measurements undertaken and the data-processing protocols applied,” it says, adding that these co-authors “have concluded that these issues undermine the integrity of the published paper”. (The Nature news team is independent from its journals team.)

It is the third high-profile retraction of a paper by the two lead authors, physicists Ranga Dias at the University of Rochester in New York and Ashkan Salamat at the University of Nevada, Las Vegas (UNLV). Nature withdrew a separate paper last year 2 and Physical Review Letters retracted one this August 3 . It spells more trouble in particular for Dias, whom some researchers allege plagiarized portions of his PhD thesis . Dias has objected to the first two retractions and not responded regarding the latest. Salamat approved the two this year.

“It is at this point hardly surprising that the team of Dias and Salamat has a third high-profile paper being retracted,” says Paul Canfield, a physicist at Iowa State University in Ames and at Ames National Laboratory. Many physicists had seen the Nature retraction as inevitable after the other two — and especially since The Wall Street Journal and Science reported in September that 8 of the 11 authors of the paper — including Salamat — had requested it in a letter to the journal.

Dias and Salamat did not respond to a request for comment by Nature ’s news team. The retraction states that he and two other co-authors — Nugzari Khalvashi-Sutter and Sasanka Munasinghe, both at Rochester — "have not stated whether they agree or disagree with this retraction".

Early scepticism

This year’s report by Dias and Salamat is the second significant claim of superconductivity to crash and burn in 2023. In July, a separate team at a start-up company in Seoul described 4 , 5 a crystalline purple material dubbed LK-99 — made of copper, lead, phosphorus and oxygen — that they said showed superconductivity at normal pressures and at temperatures up to at least 127 °C (400 kelvin). There was much online excitement and many attempts to reproduce the results, but researchers quickly reached a consensus that the material was not a superconductor at all .

LK-99 isn’t a superconductor — how science sleuths solved the mystery

Superconductors are important in many applications, from magnetic resonance imaging machines to particle colliders, but their use has been limited by the need to keep them at extremely low temperatures. For decades, researchers have been developing new materials with the dream of finding one that exhibits superconductivity without any refrigeration.

Specialists in the field have been sceptical since this year’s Dias and Salamat paper was published, says Lilia Boeri, a physicist at the Sapienza University of Rome. This, she says, is in part because of controversies swirling around the team and in part because the latest paper was not written to what she considers a high standard.

“Virtually every serious condensed-matter physicist I know saw right away that there were serious problems with the work,” says Peter Armitage, an experimental physicist at Johns Hopkins University in Baltimore, Maryland. In particular, members of the community took issue with measurements of the material’s electrical resistance, saying it was not clear whether the property truly dropped to zero, or whether Dias and Salamat had subtracted a background signal from a key plot of resistance to create the appearance that it did. Critics say that it should not be necessary to remove background from this type of measurement. In today's text, the journal stated, "An investigation by the journal and post-publication review have concluded that these concerns are credible, substantial and remain unresolved."

Stunning room-temperature-superconductor claim is retracted

Armitage adds that the publication of the paper also raises questions about the editorial review process at Nature , and why reviewers didn’t catch the issues.

“The highly qualified expert reviewers we selected raised a number of questions about the original submission, which were largely resolved in later revisions,“ says Karl Ziemelis, chief physical sciences editor at Nature . “What the peer-review process cannot detect is whether the paper as written accurately reflects the research as it was undertaken.”

“Decisions about what to accept for publication are not always easy to make,” Ziemelis continues. “And there may be conflicts, but we strive to take an unbiased position and to ensure the interests of the community always drive our deliberations.”

Audible clamour

Nature published the now-retracted paper on 8 March. That week, Dias himself presented the results to a standing-room-only audience at a meeting of the American Physical Society in Las Vegas. Over the audible clamour of the crowd assembled outside the room’s doors — where conference staff limited entry to avoid violating fire regulations — Dias briefly described a compound made of hydrogen, lutetium and small amounts of nitrogen that was a superconductor at temperatures up to 21 °C (294 kelvin) when kept at a pressure of around 1 gigapascal (10,000 times atmospheric pressure).

‘A very disturbing picture’: another retraction imminent for controversial physicist

Many teams had already created and experimented with similar hydrogen-rich materials, called hydrides, after a milestone discovery in 2015. A group led by physicist Mikhail Eremets at the Max Planck Institute for Chemistry in Mainz, Germany, reported 6 superconductivity in a hydrogen–sulfur compound at −70 °C (203 kelvin); at the time, this was a record-high operating temperature for a superconductor. But Eremets’s material required a much higher pressure of 145 gigapascals (1.4 million times atmospheric pressure) — comparable to the crushing conditions at the centre of Earth.

Since then, researchers have made hydride superconductors that push closer and closer to operating at room temperature, but all of them work only under extreme pressures. When Dias and Salamat published their paper in Nature in March, they seemed to have made a significant step towards a material that could find practical applications.

But some specialists were already wary because of the first Nature retraction . And some say they immediately found the fresh claims to be improbable. For instance, the material described in the paper was supposed to have around three hydrogen atoms for every lutetium atom. But if so, the lutetium would tend to donate an electron to each hydrogen, resulting in a kind of salt, says Artem Oganov, a materials scientist at the Skolkovo Institute of Science and Technology in Moscow. “You get either an insulator or an extremely poor metal,” he says — not a superconductor.

One lab says it has partially reproduced Dias and Salamat’s results using a sample provided by the Rochester team 7 . But many others, which tried creating their own samples and running tests, could not. And in the meantime, other causes for concern have arisen. An investigation launched by Physical Review Letters before it retracted its paper by Dias and Salamat found “apparent data fabrication”, as Nature ’s news team reported in July . And an investigation launched by Nature ’s journals team after it received an anonymous critique of data in this year’s paper found that “the credibility of the published results are in question”, according to September’s news story in Science .

Credibility concerns

Armitage does not think that Dias and Salamat will be able to keep doing research, pointing to the investigation findings and allegations of plagiarism in Dias’s PhD thesis. The University of Rochester has confirmed to Nature that it has launched an investigation into the integrity of Dias’s work, which is being conducted now by external experts. The university’s spokesperson did not answer questions about whether the institution has yet disciplined Dias. UNLV did not answer Nature ’s queries about whether Salamat is being investigated, saying that “UNLV does not publicly discuss personnel matters”, but that it “is committed to maintaining the highest standards for research integrity campus wide”.

How would room-temperature superconductors change science?

Canfield says that the Dias–Salamat collaboration has spread a “foul vapour” over the field, which “is scaring young researchers and funding agencies away”.

“I have some colleagues who simply are afraid that this case of Dias puts a shadow of doubt on the credibility of our field in general,” Eremets says.

Ho-Kwang Mao, director of the Center for High Pressure Science and Technology Advanced Research in Beijing, is more sanguine. “I do not think it will affect the funding for superconductivity research other than more careful reviews, which is not necessarily bad,” he says.

Hai-Hu Wen, director of the Center for Superconducting Physics and Materials at Nanjing University in China, agrees. “Actually, it seems more easy to get funding for the research of superconductivity since some government officials seem to be influenced by the expectation of a room-temperature superconductor,” he says.

But Boeri says she has heard researchers complain that the controversies — the allegations of PhD thesis plagiarism and the findings of apparent data fabrication — have made it harder to recruit students to work on superconductors. “We face a serious communication problem, to make people understand that the field is healthy — that although there may be some bad apples, the community’s standards are much higher,” she says.

“Serious people continue to do amazing and interesting work,” Armitage says. “Sure, they can be disheartened by this nonsense, but it won’t stop the science.”

doi: https://doi.org/10.1038/d41586-023-03398-4

Additional reporting by Lauren Wolf.

Dasenbrock-Gammon, N. et al. Nature 615 , 244–250 (2023); retraction https://doi.org/10.1038/s41586-023-06774-2 (2023).

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Snider, E. et al. Nature 586 , 373–377 (2022); retraction 610 , 804 (2022).

Durkee, D. et al. Phys. Rev. Lett. 127 , 016401 (2021); retraction 131 , 079902 (2023).

Lee, S. et al. Preprint at https://arxiv.org/abs/2307.12037 (2023).

Lee, S., Kim, J.-H. & Kwon, Y.-W. Preprint at https://arxiv.org/abs/2307.12008 (2023).

Drozdov, A. P., Eremets, M. I., Troyan, I. A., Ksenofontov, V. & Shylin, S. I. Nature 525 , 73–76 (2015).

Salke, N. P., Mark, A. C., Ahart, M. & Hemley, R. J. Preprint at https://arxiv.org/abs/2306.06301 (2023).

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