Comparative Analysis of Cas9 Activators Across Multiple Species

Several groups have generated programmable transcription factors based on the versatile Cas9 protein, yet their relative potency and effectiveness across various cell types and species remain unexplored. Here, we compare Cas9 activator systems and examine their ability to induce robust gene expression in several human, mouse, and fly cell lines. We also explore the potential for improved activation through the combination of the most potent activator systems and assess the role of cooperativity in maximizing gene expression

Measuring emotional and social wellbeing in Aboriginal and Torres Strait Islander populations: an analysis of a Negative Life Events Scale

Aboriginal and Torres Strait Islander Australians experience widespread socioeconomic disadvantage and health inequality. In an attempt to make Indigenous health research more culturally-appropriate, Aboriginal and Torres Strait Islander Australians have called for more attention to the concept of emotional and social wellbeing (ESWB). Although it has been widely recognised that ESWB is of crucial importance to the health of Aboriginal and Torres Strait Islander peoples, there is little consensus on how to measure in Indigenous populations, hampering efforts to better understand and improve the psychosocial determinants of health. This paper explores the policy and political context to this situation, and suggests ways to move forward. The second part of the paper explores how scales can be evaluated in a health research setting, including assessments of endorsement, discrimination, internal and external reliability

A global experiment on motivating social distancing during the COVID-19 pandemic

Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e., a controlling message) compared with no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared with the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing. Controlled motivation was associated with more defiance and less long-term behavioral intention to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Genetic research in Indigenous health: significant progress, substantial challenges

This article looks at the measurements and biological samples used in health research, it is the extraction and analysis of genetic material that has caused the most controversy in indigenous health research across the globe. No other kind of research has a specific international non-governmental organisation dedicated to opposing it — the Indigenous People’s Council on Biocolonialism. This United States-based organisation was founded in 1999 in the wake of the Human Genome Diversity Project (HGDP). That project was a worldwide effort to collect DNA samples from indigenous populations for population genetic research that aimed to understand the ancient migration of Homo sapiens out of Africa beginning 100 000 years ago, and populating the rest of the world

Genetics and Indigenous communities: ethical issues

 Indigenous people stand to benefit from advances in genomic technology, but genetic research in Indigenous communities has been controversial. This article reviews the ethical issues that Indigenous people and others have raised with reference to genetic research projects and biobanks. The ethical issues that apply to Indigenous people should be seen as additional to ‘conventional’ ethical issues that apply to all people, rather than replacing them. The additional ethical concerns discussed include group harm; cultural beliefs relating to biospecimens and human origins; community engagement and collective consent; benefit; ownership; and whether biospecimens can and should be ‘repatriated.&rsquo

All in the blood: a review of Aboriginal Australians\u27 cultural beliefs about blood and implications for biospecimen research

Public participation in medical research and biobanking is considered key to advances in scientific discovery and translation to improved health care. Cultural concerns relating to blood have been found to affect the participation of indigenous peoples and minorities in research, but such concerns are rarely specified in the literature. This article presents a review of the role of blood in Australian Aboriginal cultures. We discuss the range of meanings and uses of blood in traditional culture, including their use in ceremonies, healing, and sorcery. We draw on more recent literature on Aboriginal Australians and biomedicine to consider how traditional beliefs may be changing over time. These findings provide an empirical basis for researchers and bioethicists to develop culturally grounded strategies to boost the participation of Aboriginal Australians in biomedical research. They also serve as a model for integrating anthropological literature with bioethical concerns that could be applied to other indigenous and minority groups

Genetic research and Aboriginal and Torres Strait Islander Australians

While human genetic research promises to deliver a range of health benefits to the population, genetic research that takes place in Indigenous communities has proven controversial. Indigenous peoples have raised concerns, including a lack of benefit to their communities, a diversion of attention and resources from non-genetic causes of health disparities and racism in health care, a reinforcement of "victim-blaming" approaches to health inequalities, and possible misuse of blood and tissue samples. Drawing on the international literature, this article reviews the ethical issues relevant to genetic research in Indigenous populations and considers how some of these have been negotiated in a genomic research project currently under way in a remote Aboriginal community. We consider how the different levels of Indigenous research governance operating in Australia impacted on the research project and discuss whether specific guidelines for the conduct of genetic research in Aboriginal and Torres Strait Islander communities are warranted