In vivo single-cell CRISPR uncovers distinct TNF programmes in tumour evolution.

The tumour evolution model posits that malignant transformation is preceded by randomly distributed driver mutations in cancer genes, which cause clonal expansions in phenotypically normal tissues. Although clonal expansions can remodel entire tissues, the mechanisms that result in only a small number of clones transforming into malignant tumours remain unknown. Here we develop an in vivo single-cell CRISPR strategy to systematically investigate tissue-wide clonal dynamics of the 150 most frequently mutated squamous cell carcinoma genes.

Justice implications of health and food security policies for Indigenous peoples facing COVID-19: a qualitative study and policy analysis in Peru.

The spread of COVID-19 in Peru resulted in the declaration of a national health emergency, in which Indigenous peoples were identified as being particularly vulnerable due to their pre-existing poor health indicators and disadvantaged social conditions. The aim of this paper is to examine how the Peruvian government responded to the health and food needs of the Shawi and Ashaninka Indigenous peoples of Peru during the first 18 months of the pandemic (March 2020-August 2021). This study uses both official policy documents and real-world experiences to evaluate policy responses in terms of their immediate impact and their longer-term sustainability and contribution to the improvement of health, well-being and justice for Indigenous communities.

Policy responses to COVID-19 in Sri Lanka and the consideration of Indigenous Peoples.

COVID-19 has had uneven impacts on health and well-being, with Indigenous communities in the Global South facing some of the highest risks. Focusing on the experience of Sri Lanka, this study identifies key policy responses to COVID-19, documents how they evolved over two years of the pandemic, and examines if and how government responses have addressed issues pertaining to Indigenous Peoples. Drawing upon an analysis of policy documents (n = 110) and interviews with policymakers (n = 20), we characterize seven key policy responses implemented by the Sri Lankan government: i) testing for and identifying COVID-19; ii) quarantine procedures; iii) provisional clinical treatments; iv) handling other diseases during COVID-19; v) movement; vi) guidelines to be adhered to by the general public; and vii) health and vaccination.

Indigenous peoples and the COVID-19 pandemic: a systematic scoping review.

Past influenza pandemics including the Spanish flu and H1N1 have disproportionately affected Indigenous Peoples. We conducted a systematic scoping review to provide an overview of the state of understanding of the experience of Indigenous peoples during the first 18 months of the COVID-19 pandemic, in doing so we capture the state of knowledge available to governments and decision makers for addressing the needs of Indigenous peoples in these early months of the pandemic. We addressed three questions: (a) How is COVID-19 impacting the health and livelihoods of Indigenous peoples, (b) What system level challenges are Indigenous peoples experiencing, (c) How are Indigenous peoples responding? We searched Web of Science, Scopus, and PubMed databases and UN organization websites for publications about Indigenous peoples and COVID-19.

Global Catastrophic Risk and the Drivers of Scientist Attitudes Towards Policy.

An anthropogenic global catastrophic risk is a human-induced risk that threatens sustained and wide-scale loss of life and damage to civilisation across the globe. In order to understand how new research on governance mechanisms for emerging technologies might assuage such risks, it is important to ask how perceptions, beliefs, and attitudes towards the governance of global catastrophic risk within the research community shape the conduct of potentially risky research. The aim of this study is to deepen our understanding of emerging technology research culture as it relates to global catastrophic risks, and to shed new light on how new research governance mechanisms might be developed.

Interactions between climate and COVID-19.

In this Personal View, we explain the ways that climatic risks affect the transmission, perception, response, and lived experience of COVID-19. First, temperature, wind, and humidity influence the transmission of COVID-19 in ways not fully understood, although non-climatic factors appear more important than climatic factors in explaining disease transmission. Second, climatic extremes coinciding with COVID-19 have affected disease exposure, increased susceptibility of people to COVID-19, compromised emergency responses, and reduced health system resilience to multiple stresses.

Global policymakers and catastrophic risk.

There is a rapidly developing literature on risks that threaten the whole of humanity, or a large part of it. Discussion is increasingly turning to how such risks can be governed. This paper arises from a study of those involved the governance of risks from emerging technologies, examining the perceptions of global catastrophic risk within the relevant global policymaking community.

CDER risk assessment exercise to evaluate potential risks from the use of nanomaterials in drug products.

The Nanotechnology Risk Assessment Working Group in the Center for Drug Evaluation and Research (CDER) within the United States Food and Drug Administration was established to assess the possible impact of nanotechnology on drug products. The group is in the process of performing risk assessment and management exercises. The task of the working group is to identify areas where CDER may need to optimize its review practices and to develop standards to ensure review consistency for drug applications that may involve the application of nanotechnology.

Complement C1 esterase inhibitor levels linked to infections and contaminated heparin-associated adverse events.

Activation of kinin-kallikrein and complement pathways by oversulfated-chondroitin-sulfate (OSCS) has been linked with recent heparin-associated adverse clinical events. Given the fact that the majority of patients who received contaminated heparin did not experience an adverse event, it is of particular importance to determine the circumstances that increase the risk of a clinical reaction. In this study, we demonstrated by both the addition and affinity depletion of C1inh from normal human plasma, that the level of C1inh in the plasma has a great impact on the OSCS-induced kallikrein activity and its kinetics.

Gulf War Syndrome: potential role of infectious diseases.

Following the 1991 war with Iraq, some US, British, and Canadian veterans began experiencing diverse symptoms, which have been characterized as a possible 'Gulf War Syndrome'. Although veterans have been found to have a variety of illnesses, neither the existence nor etiology of a unique syndrome has been confirmed. In this review of current literature, the potential for infectious diseases to cause health problems nearly a decade after the Gulf War is evaluated.

Managing future Gulf War Syndromes: international lessons and new models of care.

After the 1991 Gulf War, veterans of the conflict from the United States, United Kingdom, Canada, Australia and other nations described chronic idiopathic symptoms that became popularly known as 'Gulf War Syndrome'. Nearly 15 years later, some 250 million dollars in United States medical research has failed to confirm a novel war-related syndrome and controversy over the existence and causes of idiopathic physical symptoms has persisted. Wartime exposures implicated as possible causes of subsequent symptoms include oil well fire smoke, infectious diseases, vaccines, chemical and biological warfare agents, depleted uranium munitions and post-traumatic stress disorder.

Resolving disputes about toxicological risks during military conflict : the US Gulf War experience.

In the last 15 years, the US and UK have fought two major wars in the Persian Gulf region. Controversy has arisen over the nature and causes of health problems among military veterans of these two wars. Toxic exposures have been hypothesised to cause the majority of the long-term health problems experienced by veterans of the 1991 Gulf War.

Treatment of Parkinson disease with diet-induced hyperketonemia: a feasibility study.

Ketones may bypass the defect in complex I activity implicated in Parkinson disease (PD). Five of seven volunteers with PD were able to prepare a "hyperketogenic" diet at home and adhere to it for 28 days. Substituting unsaturated for saturated fats appeared to prevent cholesterol increases in four volunteers.

The postwar hospitalization experience of Gulf War veterans participating in U.S. health registries.

In response to concerns that Gulf War veterans were experiencing increased morbidity resulting from wartime exposures in the Gulf War, the Department of Veterans Affairs and the Department of Defense (DoD) initiated clinical registries to provide systematic health evaluations for self-referred Gulf War veterans. The authors used Cox's proportional hazard modeling with data from all DoD hospitals to estimate the probability of hospitalization resulting from any cause, resulting from diagnosis in a major diagnostic category, and resulting from a specific diagnosis of interest. After adjusting for other risk factors, registry participants were 1.

Screening for vulnerability to psychological disorders in the military: an historical survey.

Objectives: To evaluate attempts in the military to screen for vulnerability to psychological disorders from World War I to the present.

Methods: An extensive literature review was conducted by hand-searching leading medical and psychological journals relating to World Wars I and II. Recent publications were surveyed electronically and UK archives investigated for British applications.

Mortality and postcombat disorders: U.K. veterans of the Boer War and World War I.

This study seeks to investigate the mortality rates of U.K. servicemen with postcombat syndromes following the Boer War and World War I.

Risk factors for hepatitis C virus infection among patients receiving health care in a Department of Veterans Affairs hospital.

A cross-sectional, seroepidemiological study was conducted to determine the prevalence and risk factors for hepatitis C virus (HCV) infection among veterans receiving health care from the VA. Among 274 evaluated outpatients, anti-HCV was found in 27 (9.9%).

The investigation of chronic fatigue syndrome: a case-study of the limitations of inductive inferences and non-falsifiable hypotheses in medical research.

Karl Popper's argument that deductive logic and falsifiable hypotheses are necessary for the growth of scientific knowledge has been controversial. One approach to assess the relevance of his ideas to medical science has been to evaluate examples of successful research. Another approach is to analyze an unsuccessful investigation.

Flashbacks and post-traumatic stress disorder: the genesis of a 20th-century diagnosis.

Background: It has been argued that post-traumatic stress disorder (PTSD) is a timeless condition, which existed before it was codified in modern diagnostic classifications but was described by different names such as 'railway spine' and 'shellshock'. Others have suggested that PTSD is a novel presentation that has resulted from a modern interaction between trauma and culture.

Aims: To test whether one core symptom of PTSD, the flashback, has altered in prevalence over time in soldiers subjected to the intense stress of combat.