As of August 2020, the United States is the global epicenter of the COVID-19 pandemic. Emerging data suggests that "essential" workers, who are disproportionately more likely to be racial/ethnic ...minorities and immigrants, bear a disproportionate degree of risk. We used publicly available data to build a series of spatial autoregressive models assessing county level associations between COVID-19 mortality and (1) percentage of individuals engaged in farm work, (2) percentage of households without a fluent, adult English-speaker, (3) percentage of uninsured individuals under the age of 65, and (4) percentage of individuals living at or below the federal poverty line. We further adjusted these models for total population, population density, and number of days since the first reported case in a given county. We found that across all counties that had reported a case of COVID-19 as of July 12, 2020 (n = 3024), a higher percentage of farmworkers, a higher percentage of residents living in poverty, higher density, higher population, and a higher percentage of residents over the age of 65 were all independently and significantly associated with a higher number of deaths in a county. In urban counties (n = 115), a higher percentage of farmworkers, higher density, and larger population were all associated with a higher number of deaths, while lower rates of insurance coverage in a county was independently associated with fewer deaths. In non-urban counties (n = 2909), these same patterns held true, with higher percentages of residents living in poverty and senior residents also significantly associated with more deaths. Taken together, our findings suggest that farm workers may face unique risks of contracting and dying from COVID-19, and that these risks are independent of poverty, insurance, or linguistic accessibility of COVID-19 health campaigns.
Pathological evidence for selective four-repeat (4R) tau deposition in certain dementias and exon 10-positioned MAPT mutations together suggest a 4R-specific role in causing disease. However, direct ...assessments of 4R toxicity have not yet been accomplished in vivo. Increasing 4R-tau expression without change to total tau in human tau-expressing mice induced more severe seizures and nesting behavior abnormality, increased tau phosphorylation, and produced a shift toward oligomeric tau. Exon 10 skipping could also be accomplished in vivo, providing support for a 4R-tau targeted approach to target 4R-tau toxicity and, in cases of primary MAPT mutation, eliminate the disease-causing mutation.
•Antisense oligonucleotide-mediated MAPT splicing is successful in vivo•Increasing 4R-tau induces tau phosphorylation and exacerbates seizures•Reducing 4R-tau is effective in human tau-expressing mouse models
Schoch et al. employ antisense oligonucleotide technology to manipulate tau isoforms, demonstrating that increased four-repeat tau drives toxic changes in a human tau mouse model. Reducing four-repeat tau was also achieved, suggesting application in human tauopathies.
Oil spills generate negative ecological, societal, economic, and public health impacts, and require rapid response to contain and mitigate damages. Prompt and effective emergency management of acute ...events like oil spills is highly dependent on the social, institutional, and ecological context. In August 2020, the wreckage of the MV Wakashio spilled 1000 tonnes of fuel oil along an ecologically sensitive coastline in Pointe d’Esny, Mauritius. In October 2021, an offshore pipeline split and released 78 tonnes of crude oil off the coast of Huntington Beach in California. We compare responses among three sets of stakeholders (government, non-governmental organizations, and local residents) during the first 10 days of both oil spills, which also occurred during the COVID-19 pandemic. In Mauritius, unfavorable weather conditions and COVID-19-related border closures that delayed international support impeded government action, creating a leadership and trust vacuum among residents regarding the immediate cleanup response. This perceived gap was subsequently complemented by NGOs coordinating improvised artisanal boom production and local volunteer cleanup efforts, with limited protection or public health training. By contrast, prompt state and local government intervention in Huntington Beach created a clear chain of command with NGOs and residents deferring to official guidance. In both cases, the oil spills created new policy opportunities to improve emergency management plans and reduce future risks. Our results demonstrate the influence of prior local expertise in managing earlier disasters and resources on governmental and organizational capacity. Incorporating and ensuring on-the-ground disaster expertise in response activities improves government-led crisis response, subsequently protecting ecosystems and residents. Effective multi-level crisis response helps address a range of environmental and social justice concerns related to negative impacts of spills on local communities. Our study discusses how learnings from disaster management can reinforce social-ecological resilience in coastal communities dealing with increasing anthropogenic stressors.
Each of the cardiomyopathies, classically categorized as hypertrophic cardiomyopathy, dilated cardiomyopathy (DCM), and arrhythmogenic right ventricular cardiomyopathy, has a signature genetic theme. ...Hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy are largely understood as genetic diseases of sarcomere or desmosome proteins, respectively. In contrast, >250 genes spanning >10 gene ontologies have been implicated in DCM, representing a complex and diverse genetic architecture. To clarify this, a systematic curation of evidence to establish the relationship of genes with DCM was conducted.
An international panel with clinical and scientific expertise in DCM genetics evaluated evidence supporting monogenic relationships of genes with idiopathic DCM. The panel used the Clinical Genome Resource semiquantitative gene-disease clinical validity classification framework with modifications for DCM genetics to classify genes into categories on the basis of the strength of currently available evidence. Representation of DCM genes on clinically available genetic testing panels was evaluated.
Fifty-one genes with human genetic evidence were curated. Twelve genes (23%) from 8 gene ontologies were classified as having definitive (
,
,
,
,
,
,
,
,
,
,
) or strong (
) evidence. Seven genes (14%;
,
,
,
,
,
,
) including 2 additional ontologies were classified as moderate evidence; these genes are likely to emerge as strong or definitive with additional evidence. Of these 19 genes, 6 were similarly classified for hypertrophic cardiomyopathy and 3 for arrhythmogenic right ventricular cardiomyopathy. Of the remaining 32 genes (63%), 25 (49%) had limited evidence, 4 (8%) were disputed, 2 (4%) had no disease relationship, and 1 (2%) was supported by animal model data only. Of the 16 evaluated clinical genetic testing panels, most definitive genes were included, but panels also included numerous genes with minimal human evidence.
In the curation of 51 genes, 19 had high evidence (12 definitive/strong, 7 moderate). It is notable that these 19 genes explain only a minority of cases, leaving the remainder of DCM genetic architecture incompletely addressed. Clinical genetic testing panels include most high-evidence genes; however, genes lacking robust evidence are also commonly included. We recommend that high-evidence DCM genes be used for clinical practice and that caution be exercised in the interpretation of variants in variable-evidence DCM genes.
Climate change impacts such as disasters and higher temperatures can disrupt academic learning and reduce academic performance. Here, we use two-ways linear fixed effects regression to estimate the ...effects of short-term school closures (1-5 days) due to wildfires, natural hazard impacts, infrastructure, and student safety on academic performance in California, focusing on mathematics and English scores from state assessments and college preparatory exams. Wildfires are responsible for the majority of school closures. Wildfires generate significant negative impacts on academic performance among younger students. We primarily find insignificant impacts on academic achievement due to school closures from other causes, including from the interaction between number of closure days and socioeconomic and racial/ethnic makeup of the school, across all causes. The effects of school closures lasting more than one week (6-10 days) are also generally insignificant, except for the negative impacts of wildfire closures on elementary school students. These results suggest that older students are resilient to most unexpected short-term school closures (1-5 days) or that teachers can make up lessons effectively after schoolwide closures.
Floral chemical defence strategies remain under-investigated, despite the significance of flowers to plant fitness. We used cyanogenic glycosides (CNglycs)-constitutive secondary metabolites that ...deter herbivores by releasing hydrogen cyanide, but also play other metabolic roles-to ask whether more apparent floral tissues and those most important for fitness are more defended as predicted by optimal defence theories, and what fine-scale CNglyc localisation reveals about function(s)? Florets of eleven species from the Proteaceae family were dissected to quantitatively compare the distribution of CNglycs within flowers and investigate whether distributions vary with other floral/plant traits. CNglycs were identified and their localisation in florets was revealed by matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI-MSI). We identified extremely high CNglyc content in floral tissues of several species (>1% CN), highly tissue-specific CNglyc distributions within florets, and substantial interspecific differences in content distributions, not all consistent with optimal defence hypotheses. Four patterns of within-flower CNglyc allocation were identified: greater tissue-specific allocations to (1) anthers, (2) pedicel (and gynophore), (3) pollen presenter, and (4) a more even distribution among tissues with higher content in pistils. Allocation patterns were not correlated with other floral traits (e.g. colour) or taxonomic relatedness. MALDI-MSI identified differential localisation of two tyrosine-derived CNglycs, demonstrating the importance of visualising metabolite localisation, with the diglycoside proteacin in vascular tissues, and monoglycoside dhurrin across floral tissues. High CNglyc content, and diverse, specific within-flower localisations indicate allocations are adaptive, highlighting the importance of further research into the ecological and metabolic roles of floral CNglycs.
Over the past century, scientific understanding of prescribed burns in California’s forests transitioned from being interpreted as ecologically harmful to highly beneficial. The state’s prescribed ...burn policies mirrored this evolution. Harold Biswell, a University of California at Berkeley ecologist, studied prescribed burns and became a major advocate for their use during the 1950s and 1960s. Drawing primarily on archival materials from Biswell and the state government, this historical case study presents an example of how a scientist successfully contributed to integrating research into policy and practice through consistent and targeted science communication to gain allies among environmental organizations, local stakeholders, and governments. Though at first isolated by his academic peers for proposing that fire could provide environmental benefits in forests, Biswell continued conducting and sharing his research and findings with academic and non-academic audiences. Over several decades, Biswell engaged in conversations which ultimately advanced policy changes at the state level to expand the use of prescribed burns. Despite lacking a formal role in government, Biswell used his academic platform to promote the policy implications of his research. Current and future researchers can draw on these lessons to advocate effectively for other science-informed policies.
Glycosaminoglycans (GAGs) are heterogeneous acidic polysaccharides involved in a range of biological functions. They have a significant influence on the regulation of cellular processes and the ...development of various diseases and infections. To fully understand the functional roles that GAGs play in mammalian systems, including disease processes, it is essential to understand their structural features. Despite having a linear structure and a repetitive disaccharide backbone, their structural analysis is challenging and requires elaborate preparative and analytical techniques. In particular, the extent to which GAGs are sulfated, as well as variation in sulfate position across the entire oligosaccharide or on individual monosaccharides, represents a major obstacle. Here, we summarize the current state‐of‐the‐art methodologies used for GAG sample preparation and analysis, discussing in detail liquid chromatograpy and mass spectrometry‐based approaches, including advanced ion activation methods, ion mobility separations and infrared action spectroscopy of mass‐selected species.
To systematically study the number of U.S. resident deaths from all causes, including suicide.
The more than 9,900 programs accredited by the Accreditation Council for Graduate Medical Education ...(ACGME) annually report the status of residents. The authors aggregated ACGME data on 381,614 residents in training during years 2000 through 2014. Names of residents reported as deceased were submitted to the National Death Index to learn causes of death. Person-year calculations were used to establish resident death rates and compare them with those in the general population.
Between 2000 and 2014, 324 individuals (220 men, 104 women) died while in residency. The leading cause of death was neoplastic disease, followed by suicide, accidents, and other diseases. For male residents the leading cause was suicide, and for female residents, malignancies. Resident death rates were lower than in the age- and gender-matched general population. Temporal patterns showed higher rates of death early in residency. Deaths by suicide were higher early in training, and during the first and third quarters of the academic year. There was no upward or downward trend in resident deaths over the 15 years of this study.
Neoplastic disease and suicide were the leading causes of death in residents. Data for death by suicide suggest added risk early in residency and during certain months of the academic year. Providing trainees with a supportive environment and with medical and mental health services is integral to reducing preventable deaths and fostering a healthy physician workforce.
PDF
