Characteristics and Outcomes of People With Gout Hospitalized Due to COVID-19: Data From the COVID-19 Global Rheumatology Alliance Physician-Reported Registry

Objective: To describe people with gout who were diagnosed with coronavirus disease 2019 (COVID-19) and hospitalized and to characterize their outcomes. Methods: Data on patients with gout hospitalized for COVID-19 between March 12, 2020, and October 25, 2021, were extracted from the COVID-19 Global Rheumatology Alliance registry. Descriptive statistics were used to describe the demographics, comorbidities, medication exposures, and COVID-19 outcomes including oxygenation or ventilation support and death. Results: One hundred sixty-three patients with gout who developed COVID-19 and were hospitalized were included. The mean age was 63 years, and 85% were male. The majority of the group lived in the Western Pacific Region (35%) and North America (18%). Nearly half (46%) had two or more comorbidities, with hypertension (56%), cardiovascular disease (28%), diabetes mellitus (26%), chronic kidney disease (25%), and obesity (23%) being the most common. Glucocorticoids and colchicine were used pre-COVID-19 in 11% and 12% of the cohort, respectively. Over two thirds (68%) of the cohort required supplemental oxygen or ventilatory support during hospitalization. COVID-19-related death was reported in 16% of the overall cohort, with 73% of deaths documented in people with two or more comorbidities. Conclusion: This cohort of people with gout and COVID-19 who were hospitalized had high frequencies of ventilatory support and death. This suggests that patients with gout who were hospitalized for COVID-19 may be at risk of poor outcomes, perhaps related to known risk factors for poor outcomes, such as age and presence of comorbidity

Effects of Alcohol on the Acquisition and Expression of Fear Potentiated Startle in Mouse Lines Selectively Bred for High and Low Alcohol Preference

Rationale: Anxiety disorders and alcohol-use disorders frequently co-occur in humans perhaps because alcohol relieves anxiety. Studies in humans and rats indicate that alcohol may have greater anxiolytic effects in organisms with increased genetic propensity for high alcohol consumption. Objectives and Methods: The purpose of this study was to investigate the effects of moderate doses of alcohol (0.5, 1.0, 1.5 g/kg) on the acquisition and expression of anxiety-related behavior using a fear-potentiated startle (FPS) procedure. Experiments were conducted in two replicate pairs of mouse lines selectively bred for high- (HAP1 and HAP2) and low- (LAP1 and LAP2) alcohol preference; these lines have previously shown a genetic correlation between alcohol preference and FPS (HAP\u3eLAP; Barrenha and Chester 2007). In a control experiment, the effect of diazepam (4.0 mg/kg) on the expression of FPS was tested in HAP2 and LAP2 mice. Results: The 1.5 g/kg alcohol dose moderately decreased the expression of FPS in both HAP lines but not LAP lines. Alcohol had no effect on the acquisition of FPS in any line. Diazepam reduced FPS to a similar extent in both HAP2 and LAP2 mice. Conclusions: HAP mice may be more sensitive to the anxiolytic effects of alcohol than LAP mice when alcohol is given prior to the expression of FPS. These data collected in two pairs of HAP/LAP mouse lines suggest that the anxiolytic response to alcohol in HAP mice may be genetically correlated with their propensity toward high alcohol preference and robust FPS

Luminescence Dating in Fluvial Settings: Overcoming the Challenge of Partial Bleaching

Optically stimulated luminescence (OSL) dating is a versatile technique that utilises the two most ubiquitous minerals on Earth (quartz or K-feldspar) for constraining the timing of sediment deposition. It has provided accurate ages in agreement with independent age control in many fluvial settings, but is often characterised by partial bleaching of individual grains. Partial bleaching can occur where sunlight exposure is limited and so only a portion of the grains in the sample was exposed to sunlight prior to burial, especially in sediment-laden, turbulent or deep water columns. OSL analysis on multiple grains can provide accurate ages for partially bleached sediments where the OSL signal intensity is dominated by a single brighter grain, but will overestimate the age where the OSL signal intensity is equally as bright (often typical of K-feldspar) or as dim (sometimes typical of quartz). In such settings, it is important to identify partial bleaching and the minimum dose population, preferably by analysing single grains, and applying the appropriate statistical age model to the dose population obtained for each sample. To determine accurate OSL ages using these age models, it is important to quantify the amount of scatter (or overdispersion) in the well-bleached part of the partially bleached dose distribution, which can vary between sediment samples depending upon the bedrock sources and transport histories of grains. Here, we discuss how the effects of partial bleaching can be easily identified and overcome to determine accurate ages. This discussion will therefore focus entirely on the burial dose determination for OSL dating, rather than the dose-rate, as only the burial doses are impacted by the effects of partial bleaching

Association analysis identifies 65 new breast cancer risk loci

Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry. We identified 65 new loci that are associated with overall breast cancer risk at P < 5 × 10-8. The majority of credible risk single-nucleotide polymorphisms in these loci fall in distal regulatory elements, and by integrating in silico data to predict target genes in breast cells at each locus, we demonstrate a strong overlap between candidate target genes and somatic driver genes in breast tumours. We also find that heritability of breast cancer due to all single-nucleotide polymorphisms in regulatory features was 2-5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the use of genetic risk scores for individualized screening and prevention.We thank all the individuals who took part in these studies and all the researchers, clinicians, technicians and administrative staff who have enabled this work to be carried out. Genotyping of the OncoArray was principally funded from three sources: the PERSPECTIVE project, funded by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research, the ‘Ministère de l’Économie, de la Science et de l’Innovation du Québec’ through Genome Québec, and the Quebec Breast Cancer Foundation; the NCI Genetic Associations and Mechanisms in Oncology (GAME-ON) initiative and Discovery, Biology and Risk of Inherited Variants in Breast Cancer (DRIVE) project (NIH Grants U19 CA148065 and X01HG007492); and Cancer Research UK (C1287/A10118 and C1287/A16563). BCAC is funded by Cancer Research UK (C1287/A16563), by the European Community’s Seventh Framework Programme under grant agreement 223175 (HEALTH-F2-2009-223175) (COGS) and by the European Union’s Horizon 2020 Research and Innovation Programme under grant agreements 633784 (B-CAST) and 634935 (BRIDGES). Genotyping of the iCOGS array was funded by the European Union (HEALTH-F2-2009-223175), Cancer Research UK (C1287/A10710), the Canadian Institutes of Health Research for the ‘CIHR Team in Familial Risks of Breast Cancer’ program, and the Ministry of Economic Development, Innovation and Export Trade of Quebec, grant PSR-SIIRI-701. Combining of the GWAS data was supported in part by The National Institute of Health (NIH) Cancer Post-Cancer GWAS initiative grant U19 CA 148065 (DRIVE, part of the GAME-ON initiative)

Analysis of late Quaternary linear dune development in the Thar Desert, India

Linear dunes are the most widespread dune type worldwide and act as important geoproxies of late Quaternary environmental change in deserts. They are less common in the Thar Desert, India than other dune types, especially parabolic forms, and to date their development history is poorly understood. Here we investigate a linear dunefield in the northern Thar through analysis of a series of excavated full dune profile sites and the application of optically stimulated luminescence (OSL) dating to provide chronometric control. Results show that linear dunes have been present since at least ~58 ka and were active throughout much of the Holocene. The early Holocene, a period marked by strong Indian summer monsoon winds (e.g., Gill et al., 2017), has been shown as the last major phase of dune accumulation recorded in all sites, with ages ranging from ~11.6–8.6 ka. Two spatially restricted records of dune accumulation have also been identified during the later part of Holocene: ~4–3 ka and ~2–1 ka, attributed to localised reworking within the dunes. The suite of luminescence ages generated from the study region confirms the principle recognised in other dunefields (e.g., the south-western Kalahari; Stone and Thomas, 2008) and theoretically (Bailey and Thomas, 2014) that age records from individual dunes are unlikely to capture the developmental history of dunefields

Holocene dune activity in the Thar Desert, India

The Thar Desert dune system in north-west India and eastern Pakistan provides a rich archive of past environmental, geomorphological and climatic change. Much of the knowledge about the timing of dune accumulation in the Thar stems from scattered and sporadic records, based on older luminescence dating protocols. If the Thar dune record is to be incorporated within a growing multiproxy framework of past climate and environmental dynamics, it is necessary to generate a systematic record of the timing of dunefield accumulation. From this, relationships to climate and other drivers of dune activity may then be better established. To this end, an intensive programme of field sampling and optically stimulated luminescence (OSL) dating was carried out from a dunefield in the east-central Thar Desert. This study presents the first detailed Holocene dune accumulation history from the region, and sheds light on the development of the multi-generational parabolic dune systems. In contrast to previously published work, we identify the importance of the Holocene and the last millennium as periods with a number of preserved accumulation phases. OSL ages suggest that accumulation was persistent during the early and mid-Holocene (within 11.7-5.5 ka), late Holocene (2-1 ka), as well as two major phases in the last millennium (600 – 200 a and within the last 70 a). Potential drivers of dune mobility in the last century include a strong anthropogenic dimension. Rapid net accumulation is recorded in the last 70 years, with rates varying between 2 and 5 m/year, in an environment where agricultural pressures have increased dramatically with the advent of irrigation schemes expanding into dunefield areas. © 2019 John Wiley &amp; Sons, Ltd

Geoarchaeological insights into the location of Indus settlements on the plains of northwest India

This article presents a geomorphological and micromorphological study of the locational context of four Indus civilisation archaeological sites—Alamgirpur, Masudpur I and VII, and Burj—all situated on the Sutlej-Yamuna interfluve in northwest India. The analysis indicates a strong correlation between settlement foundation and particular landscape positions on an extensive alluvial floodplain. Each of the analysed sites was located on sandy levees and/or riverbank deposits associated with former channels. These landscape positions would have situated settlements above the level of seasonal floodwater resulting from the Indian summer monsoon. In addition, the sandy soils on the margins of these elevated landscape positions would have been seasonally replenished with water, silt, clay, and fine organic matter, considerably enhancing their capacity for water retention and fertility and making them particularly suitable for agriculture. These former landscapes are obscured by recent modification and extensive agricultural practices. These geoarchaeological evaluations indicate that there is a hidden landscape context for each Indus settlement. This specific type of interaction between humans and their local context is an important aspect of Indus cultural adaptations to diverse, variable, and changing environments