A call from 40 public health scientists for an end to the continuing humanitarian and environmental catastrophe in Gaza.

An under-recognised aspect of the current humanitarian catastrophe in Gaza is the impact of the war on the environment and the associated risks for human health. This commentary contextualises these impacts against the background of human suffering produced by the overwhelming violence associated with the use of military force against the general population of Gaza. In calling for an immediate cessation to the violence, the authors draw attention to the urgent need to rebuild the health care system and restore the physical and human infrastructure that makes a liveable environment possible and promotes human health and well-being, especially for the most vulnerable in the population. Environmental remediation should therefore form one of the most important parts of international efforts to assist reconstruction, through which we hope Palestinians and Israelis will achieve lasting peace, health, and sustainable development, all as part of accepted international human rights obligations.

An evaluation of clinical presentation and genetic testing approaches for patients with neuromuscular disorders.

Inherited neuromuscular disorders (NMDs) are a large group of genetic conditions characterized by impaired peripheral nerve, motor neuron, neuromuscular junction, or skeletal muscle function. These conditions are also known to have clinical and genetic heterogeneity and variable ages of onset. Clinical evaluation for NMDs has increasingly incorporated molecular genetics. However, genetic testing is complicated by the variety of testing options and the ambiguity of NMD phenotypes. Examining test selection and yield may elucidate testing recommendations and improve the diagnostic journey for these patients. This retrospective chart review evaluated the clinical presentations, genetic testing approaches, and diagnostic outcomes of 155 patients with suspected NMDs at Cincinnati Children's Hospital Medical Center. A total of 262 individual tests were ordered, averaging 1.7 tests per patient. The clinic utilized 26 separate genetic tests, with test yields ranging from 0% to 66%. Overall, 21% of patients received a genetic diagnosis. Of all the clinical findings evaluated, elevated CPK levels with or without muscle weakness were the most informative symptoms correlated with a diagnostic result. This study highlights several genetic testing considerations for NMDs, including the variability of diagnostic outcomes. This knowledge is relevant to clinicians and patients, especially during the pretest counseling and consenting process.

Early validity and reliability evidence for the American Board of Emergency Medicine Virtual Oral Examination.

Background: The American Board of Emergency Medicine (ABEM) in-person Oral Certification Examination (OCE) was halted abruptly in 2020 due to the COVID-19 pandemic. The OCE was reconfigured to be administered in a virtual environment starting in December 2020. Objectives: The purpose of this investigation was to determine whether there was sufficient validity and reliability evidence to support the continued use of the ABEM virtual Oral Examination (VOE) for certification decisions. Methods: This retrospective, descriptive study used multiple data sources to provide validity evidence and reliability data. Validity evidence focused on test content, response processes, internal structure (e.g., internal consistency and item response theory), and the consequences of testing. A multifaceted Rasch reliability coefficient was used to measure reliability. Study data were from two 2019 in-person OCEs and the first four VOE administrations. Results: There were 2279 physicians who took the 2019 in-person OCE examination and 2153 physicians who took the VOE during the study period. Among the OCE group, 92.0% agreed or strongly agreed that the cases on the examination were cases that an emergency physician should be expected to see; 91.1% of the VOE group agreed or strongly agreed. A similar pattern of responses given to a question about whether the cases on the examination were cases that they had seen. Additional evidence of validity was obtained by the use of the EM Model, the process for case development, the use of think-aloud protocols, and similar test performance patterns (e.g., pass rates). For reliability, the Rasch reliability coefficients for the OCE and the VOE during the study period were all >0.90. Conclusions: There was substantial validity evidence and reliability to support ongoing use of the ABEM VOE to make confident and defensible certification decisions.

Cellular and molecular characterization of two novel asparagine synthetase gene mutations linked to asparagine synthetase deficiency.

Asparagine synthetase (ASNS) catalyzes synthesis of asparagine (Asn) and Glu from Asp and Gln in an ATP-dependent reaction. Asparagine synthetase deficiency (ASNSD) results from biallelic mutations in the ASNS gene. Affected children exhibit congenital microcephaly, continued brain atrophy, seizures, and often premature mortality. However, the underlying mechanisms are unclear. This report describes a compound heterozygotic ASNSD child with two novel mutations in the ASNS gene, c.1118G>T (paternal) and c.1556G>A (maternal), that lead to G373V or R519H ASNS variants. Structural mapping suggested that neither variant participates directly in catalysis. Growth of cultured fibroblasts from either parent was unaffected in Asn-free medium, whereas growth of the child's cells was suppressed by about 50%. Analysis of Asn levels unexpectedly revealed that extracellular rather than intracellular Asn correlated with the reduced proliferation during incubation of the child's cells in Asn-free medium. Our attempts to ectopically express the G373V variant in either HEK293T or JRS cells resulted in minimal protein production, suggesting instability. Protein expression and purification from HEK293T cells revealed reduced activity for the R519H variant relative to WT ASNS. Expression of WT ASNS in ASNS-null JRS cells resulted in nearly complete rescue of growth in Asn-free medium, whereas we observed no proliferation for the cells expressing either the G373V or R519H variant. These results support the conclusion that the coexpression of the G373V and R519H ASNS variants leads to significantly reduced Asn synthesis, which negatively impacts cellular growth. These observations are consistent with the ASNSD phenotype.

Caregivers of individuals with Rubinstein-Taybi syndrome: Perspectives, experiences, and relationships with medical professionals.

Rubinstein-Taybi syndrome (RTS) is a rare genetic disorder. Family-centered care (FCC) is a healthcare delivery approach that aims to create an equal partnership between caregivers and providers. FCC has been shown to improve parental wellbeing, their knowledge of the condition and care, and improve their feelings of self-efficacy and personal control. The purpose of this study was to explore the healthcare experiences of family caregivers of children and adults with RTS to understand the issues they encounter when working with medical professionals and to examine their perspectives on how to improve FCC. Primary family caregivers of individuals with RTS took an online mixed-method survey that contained three primary components: a demographic survey, the Measures of Processes of Care-20 (MPOC-20) [a measure of the FCC an individual feels they receive], and a qualitative assessment of negative and positive interactions with medical professionals and priority areas for improvement. Qualitative data were analyzed using thematic analysis. Quantitative data were analyzed with descriptive statistics. An analysis of variance test was used to determine whether values statistically differed between different-age groups of individuals with RTS being cared for. Sixty-three caregivers completed the survey. The average score of the Providing General Information subscale of the MPOC-20 was 3.18, lower than that seen in other studies. The average scores of the other subscales of the MPOC-20 ranged from 4.60 to 5.02, comparable to other studies of caregivers of children with other medical conditions. All aspects of FCC were ranked as important by caregivers. There were no differences in MPOC-20 values between those caring for the individuals with RTS in different-age groups reviewed. In the qualitative responses, parents noted that experiences with medical professionals would be improved if healthcare providers actively provided FCC, collaborated with parents and other providers, respected caregivers' time and breadth of knowledge and lived experience, gave a more balanced description of the condition, showed greater respect toward their loved ones and included them in the conversation, and made an effort to learn about RTS. The changes that parents would like to see in their child's care were not specific to one discipline and could be implemented by all healthcare specialists. While caregivers report that they receive moderate levels of FCC, they indicated that areas of FCC could be improved.

How Canada Changed from Exporting Asbestos to Banning Asbestos: The Challenges That Had to Be Overcome.

Less than ten years ago, the asbestos industry enjoyed the support of every Quebec and Canadian political party. The Chrysotile Institute and the International Chrysotile Association, both located in Quebec, aggressively marketed asbestos around the world, claiming scientific evidence showed that chrysotile asbestos could be safely used. The industry created a climate of intimidation. Consequently, no groups advocating for victims of asbestos or campaigning for its outright ban existed in Quebec to challenge the industry. A campaign was launched to mobilize the scientific community to speak out. Working with scientists, activists, and asbestos victims around the world, a small group of Quebec scientists exposed the false arguments of the asbestos industry. They publicly and repeatedly challenged the unscientific and unethical asbestos policy of the government. By appealing to Quebec values and holding those in power accountable, the campaign won public support and succeeded against all odds in defeating the asbestos industry.

How Canada's Asbestos Industry Was Defeated in Quebec.

Less than a decade ago, the Quebec asbestos industry enjoyed support from all the political parties in the Canadian House of Commons and the Quebec National Assembly, as well as from business and union organizations. Two lobby organizations (Chrysotile Institute and International Chrysotile Association) had significant global impact in promoting asbestos use and defeating asbestos ban efforts in developing countries. Quebec's two asbestos mines planned to expand operations and make Quebec the second biggest global asbestos exporter. With the aid of lobbyists, public relations consultants, and government financing, the asbestos industry came close to succeeding. The article examines how a campaign of international solidarity, involving scientific experts, asbestos victims, and health activists in Quebec, Canada, and overseas, succeeded in closing the two mines and defeating the political and social power that the Quebec asbestos industry had wielded for a century. This victory ended Canada's destructive role as global propagandist for the asbestos industry.

Scientific journal publishes second eratum regarding false information by scientists funded by asbestos interests.

In a paper published on Epidemiology, Biostatistics and Public Health, Ilgren et al. claimed that cases of mesothelioma among workers of the Balangero (a municipality of the province of Turin, Northern Italy) chrysotile mine and nearby residents were not caused by chrysotile, but by other forms of asbestos. In support, they cited a reference where no pertaining evidence can be found. One year after the paper, an erratum was published by the journal editors in chief, warning that an erroneous citation was present. The erratum is weak and misleading, concealing the fact that a false statement was supported by such error and that it may serve the interests of the chrysotile industry, by dismissing evidence of chrysotile carcinogenicity. Some of the article authors, of the editors in chief and members of the journal editorial board had financial ties to asbestos interests.

Scientific journals and conflict of interest disclosure: what progress has been made?

The article addresses the failure of the scientific community to create an effective mechanism to protect the integrity of the scientific literature from improper influence by vested interests. The seriousness of this threat is increasingly recognized. Scientists willing to distort scientific research to serve vested interests receive millions of dollars for their services. Organizations such as the International Committee of Medical Journal Editors, the World Association of Medical Editors and the Committee on Publication Ethics (COPE) have launched initiatives to establish international standards for Conflict of Interest (COI) disclosure. COPE requires its 7,000 member journals to comply with its Code of Conduct for Journal Editors. While these initiatives are encouraging, they are internal educational endeavours only. Five examples are given showing failure of COPE member journals to comply with COPE's Code of Conduct. While COPE offers a complaint process, it involves only discussion and voluntary compliance. COPE neither polices nor enforces its Code. Instead of the current feeble, un-resourced process, which delivers neither transparency nor accountability, the article proposes the creation of a mechanism that will employ specific, effective measures to address contraventions of COI disclosure requirements.

Ethics, morality, and conflicting interests: how questionable professional integrity in some scientists supports global corporate influence in public health.

Clinical and public health research, education, and medical practice are vulnerable to influence by corporate interests driven by the for-profit motive. Developments over the last 10 years have shown that transparency and self-reporting of corporate ties do not always mitigate bias. In this article, we provide examples of how sound scientific reasoning and evidence-gathering are undermined through compromised scientific enquiry resulting in misleading science, decision-making, and policy intervention. Various medical disciplines provide reference literature essential for informing public, environmental, and occupational health policy. Published literature impacts clinical and laboratory methods, the validity of respective clinical guidelines, and the development and implementation of public health regulations. Said literature is also used in expert testimony related to resolving tort actions on work-related illnesses and environmental risks. We call for increased sensitivity, full transparency, and the implementation of effective ethical and professional praxis rules at all relevant regulatory levels to rout out inappropriate corporate influence in science. This is needed because influencing the integrity of scientists who engage in such activities cannot be depended upon.

Conflict of interest, tailored science, and responsibility of scientific institutions and journals.

Recent revelations have raised concerns on how conflicts of interest may involve even leading scientists and prestigious institutions and lead to bias in reporting and assessing scientific evidence. These have highlighted the need for action to safeguard scientific integrity and public health. The Italian Epidemiology Association has declared that the "biased and deliberately tailored use of the scientific evidence" by scientists with a conflict of interest serves to delay needed measures to prevent harm to public health from a polluting Italian steel plant's continuing chemical emissions. In France, unresolved concerns over conflict of interest forced the Centre for Research in Epidemiology and Public Health to cancel its imminent appointment of a prominent scientist as its Director. These negative events demonstrate the necessity for scientific institutions and journals to implement rigorous measures regarding conflict of interest and the safeguarding of scientific integrity and public health.