Psychological Impairment and Extreme Weather Event (EWE) Exposure, 1980–2020: A Global Pooled Analysis Integrating Mental Health and Well-being Metrics

Extreme Weather Events (EWEs) impose a substantial health and socio-economic burden on exposed populations. Projected impacts on public health, based on increasing EWE frequencies since the 1950s, alongside evidence of human-mediated climatic change represents a growing concern. To date, the impacts of EWEs on mental health remain ambiguous, largely due to the inherent complexities in linking extreme weather phenomena with psychological status. This exploratory investigation provides a new empirical and global perspective on the psychological toll of EWEs by exclusively focusing on psychological morbidity among individuals exposed to such events. Morbidity data collated from a range of existing psychological and well-being measures have been integrated to develop a single (“holistic”) metric, namely, psychological impairment. Morbidity, and impairment, were subsequently pooled for key disorders-, specifically PTSD, anxiety and depression. A “composite” (any impairment) post-exposure pooled-prevalence rate of 23% was estimated, with values of 24% calculated for depression and ⁓17% for both PTSD and anxiety. Notably, calculated pooled odds ratios (pOR = 1.9) indicate a high likelihood of any negative psychological outcome (+90%) following EWE exposure. Pooled analyses of reported risk factors (p \u3c 0.05) highlight the pronounced impacts of EWEs among individuals with higher levels of event exposure or experienced stressors (14.5%) and socio-demographic traits traditionally linked to vulnerable sub-populations, including female gender (10%), previous history (i.e., pre-event) of psychological impairment (5.5%), lower socio-economic status (5.5%), and a lower education level (5.2%). Inherent limitations associated with collating mental health data from populations exposed to EWEs, and key knowledge gaps in the field are highlighted. Study findings provide a robust evidence base for developing and implementing public health intervention strategies aimed at ameliorating the psychological impacts of extreme weather among exposed populations

Network segregation in a model of misinformation and fact checking

Misinformation under the form of rumor, hoaxes, and conspiracy theories spreads on social media at alarming rates. One hypothesis is that, since social media are shaped by homophily, belief in misinformation may be more likely to thrive on those social circles that are segregated from the rest of the network. One possible antidote is fact checking which, in some cases, is known to stop rumors from spreading further. However, fact checking may also backfire and reinforce the belief in a hoax. Here we take into account the combination of network segregation, finite memory and attention, and fact-checking efforts. We consider a compartmental model of two interacting epidemic processes over a network that is segregated between gullible and skeptic users. Extensive simulation and mean-field analysis show that a more segregated network facilitates the spread of a hoax only at low forgetting rates, but has no effect when agents forget at faster rates. This finding may inform the development of mitigation techniques and overall inform on the risks of uncontrolled misinformation online

Sustaining the Digital Humanities in the UK

The Sustaining Digital Humanities in the UK report is timely for the UK Digital Humanities (DH) landscape. The establishment of UK Research and Innovation (UKRI) has created an opportune moment for the strategic planning of research infrastructure between and across all the research areas. Led by Giles Bergel and Pip Willcox, this report is based on the findings of a workshop held at the University of Oxford’s e-Research Centre (OeRC) on 21 June 2018 and sponsored by the Software Sustainability Institute. The workshop was led by an advisory board of Digital Humanities practitioners, representing a range of career stages, roles, and disciplines. The workshop’s organisers and advisory board are the joint authors of this report, with contributions from workshop participants. The mission of the Software Sustainability Institute (SSI) is to cultivate better, more sustainable, research software to enable world-class research. Currently celebrating its 10th year, the SSI has achieved broadening engagement across academic communities including humanities – for example as a longstanding supporter of the Digital Humanities at Oxford Summer School (DHOxSS), and with SSI Fellows in the arts and humanities areas. This report was commissioned by the SSI with the aim of advancing its mission within the humanities. Digital Humanities, a broad intersection of models, methods, tools, materials, career paths and affiliations, in both established and novel disciplines was identified as the area within the humanities that most closely aligns with the SSI’s role

Overcoming Barriers to Vaccination By Empowering Citizens to Make Deliberate Choices

Copyright © The authors. Overcoming Barriers to Vaccination By Empowering Citizens to Make Deliberate Choices is one of ten in-depth transatlantic reports published by The British Academy exploring COVID-19 vaccine engagement in the UK and the US. For more details, see: https://www.thebritishacademy.ac.uk/news/the-british-academy-publishes-studies-examining-covid-vaccine-engagement-in-uk-and-usa/.British Academy (COVG7210005); Department for Business, Energy and Industrial Strategy.https://www.thebritishacademy.ac.uk/news/the-british-academy-publishes-studies-examining-covid-vaccine-engagement-in-uk-and-usa

Author Correction: A consensus-based transparency checklist.

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Reduced levels of dopamine and altered metabolism in brains of HPRT knock-out rats: a new rodent model of Lesch-Nyhan Disease

Lesch-Nyhan disease (LND) is a severe neurological disorder caused by loss-of-function mutations in the gene encoding hypoxanthine phosphoribosyltransferase (HPRT), an enzyme required for efficient recycling of purine nucleotides. Although this biochemical defect reconfigures purine metabolism and leads to elevated levels of the breakdown product urea, it remains unclear exactly how loss of HPRT activity disrupts brain function. As the rat is the preferred rodent experimental model for studying neurobiology and diseases of the brain, we used genetically-modified embryonic stem cells to generate an HPRT knock-out rat. Male HPRT-deficient rats were viable, fertile and displayed normal caged behaviour. However, metabolomic analysis revealed changes in brain biochemistry consistent with disruption of purine recycling and nucleotide metabolism. Broader changes in brain biochemistry were also indicated by increased levels of the core metabolite citrate and reduced levels of lipids and fatty acids. Targeted MS/MS analysis identified reduced levels of dopamine in the brains of HPRT-deficient animals, consistent with deficits noted previously in human LND patients and HPRT knock-out mice. The HPRT-deficient rat therefore provides a new experimental platform for future investigation of how HPRT activity and disruption of purine metabolism affects neural function and behaviour

Induction of autophagy is a key component of all-trans-retinoic acid-induced differentiation in leukemia cells and a potential target for pharmacological modulation

Acute myeloid leukemia (AML) is characterized by the accumulation of immature blood cell precursors in the bone marrow. Pharmacologically overcoming the differentiation block in this condition is an attractive therapeutic avenue, which has achieved success only in a subtype of AML, acute promyelocytic leukemia (APL). Attempts to emulate this success in other AML subtypes have thus far been unsuccessful. Autophagy is a conserved protein degradation pathway with important roles in mammalian cell differentiation, particularly within the hematopoietic system. In the study described here, we investigated the functional importance of autophagy in APL cell differentiation. We found that autophagy is increased during all-trans-retinoic acid (ATRA)-induced granulocytic differentiation of the APL cell line NB4 and that this is associated with increased expression of LC3II and GATE-16 proteins involved in autophagosome formation. Autophagy inhibition, using either drugs (chloroquine/3-methyladenine) or short-hairpin RNA targeting the essential autophagy gene ATG7, attenuates myeloid differentiation. Importantly, we found that enhancing autophagy promotes ATRA-induced granulocytic differentiation of an ATRA-resistant derivative of the non-APL AML HL60 cell line (HL60-Diff-R). These data support the development of strategies to stimulate autophagy as a novel approach to promote differentiation in AML

Like-minded sources on Facebook are prevalent but not polarizing

Many critics raise concerns about the prevalence of ‘echo chambers’ on social media and their potential role in increasing political polarization. However, the lack of available data and the challenges of conducting large-scale field experiments have made it difficult to assess the scope of the problem 1,2. Here we present data from 2020 for the entire population of active adult Facebook users in the USA showing that content from ‘like-minded’ sources constitutes the majority of what people see on the platform, although political information and news represent only a small fraction of these exposures. To evaluate a potential response to concerns about the effects of echo chambers, we conducted a multi-wave field experiment on Facebook among 23,377 users for whom we reduced exposure to content from like-minded sources during the 2020 US presidential election by about one-third. We found that the intervention increased their exposure to content from cross-cutting sources and decreased exposure to uncivil language, but had no measurable effects on eight preregistered attitudinal measures such as affective polarization, ideological extremity, candidate evaluations and belief in false claims. These precisely estimated results suggest that although exposure to content from like-minded sources on social media is common, reducing its prevalence during the 2020 US presidential election did not correspondingly reduce polarization in beliefs or attitudes

Adenoviral-mediated correction of methylmalonyl-CoA mutase deficiency in murine fibroblasts and human hepatocytes

<p>Abstract</p> <p>Background</p> <p>Methylmalonic acidemia (MMA), a common organic aciduria, is caused by deficiency of the mitochondrial localized, 5'deoxyadenosylcobalamin dependent enzyme, methylmalonyl-CoA mutase (MUT). Liver transplantation in the absence of gross hepatic dysfunction provides supportive therapy and metabolic stability in severely affected patients, which invites the concept of using cell and gene delivery as future treatments for this condition.</p> <p>Methods</p> <p>To assess the effectiveness of gene delivery to restore the defective metabolism in this disorder, adenoviral correction experiments were performed using murine <it>Mut </it>embryonic fibroblasts and primary human methylmalonyl-CoA mutase deficient hepatocytes derived from a patient who harbored two early truncating mutations, E224X and R228X, in the <it>MUT </it>gene. Enzymatic and expression studies were used to assess the extent of functional correction.</p> <p>Results</p> <p>Primary hepatocytes, isolated from the native liver after removal subsequent to a combined liver-kidney transplantation procedure, or <it>Mut </it>murine fibroblasts were infected with a second generation recombinant adenoviral vector that expressed the murine methylmalonyl-CoA mutase as well as eGFP from distinct promoters. After transduction, [1-¹⁴C] propionate macromolecular incorporation studies and Western analysis demonstrated complete correction of the enzymatic defect in both cell types. Viral reconstitution of enzymatic expression in the human methylmalonyl-CoA mutase deficient hepatocytes exceeded that seen in fibroblasts or control hepatocytes.</p> <p>Conclusion</p> <p>These experiments provide proof of principle for viral correction in methylmalonic acidemia and suggest that hepatocyte-directed gene delivery will be an effective therapeutic treatment strategy in both murine models and in human patients. Primary hepatocytes from a liver that was unsuitable for transplantation provided an important resource for these studies.</p