Genotyping concordance in DNA extracted from formalin‐fixed paraffin embedded (FFPE) breast tumor and whole blood for pharmacogenetic analyses

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135708/1/mol22015991868.pd

Feasibility and acceptability of a technology-based, rural weight management int ervention in older adults with obesity

Background Older adults with obesity residing in rural areas have reduced access to weight management programs. We determined the feasibility, acceptability and preliminary outcomes of an integrated technology-based health promotion intervention in rural-living, older adults using remote monitoring and synchronous video-based technology. Methods A 6-month, non-randomized, non-blinded, single-arm study was conducted from October 2018 to May 2020 at a community-based aging center of adults aged ≥65 years with a body mass index (BMI) ≥30 kg/m2. Weekly dietitian visits focusing on behavior therapy and caloric restriction and twice-weekly physical therapist-led group strength, flexibility and balance training classes were delivered using video-conferencing to participants in their homes. Participants used a Fitbit Alta HR for remote monitoring with data feedback provided by the interventionists. An aerobic activity prescription was provided and monitored. Results Mean age was 72.9±3.9 years (82% female). Baseline anthropometric measures of weight, BMI, and waist circumference were 97.8±16.3 kg, 36.5±5.2 kg/m2, and 115.5±13.0 cm, respectively. A total of 142 participants were screened (n=27 ineligible), and 53 consented. There were nine dropouts (17%). Overall satisfaction with the trial (4.7+ 0.6, scale: 1 (low) to 5 (high)) and with Fitbit (4.2+ 0.9) were high. Fitbit was worn an average of 81.7±19.3% of intervention days. In completers, mean weight loss was 4.6±3.5 kg or 4.7±3.5% (p\u3c 0.001). Physical function measures of 30-s sit-to-stand repetitions increased from 13.5±5.7 to 16.7±5.9 (p\u3c 0.001), 6-min walk improved by 42.0±77.3 m (p=0.005) but no differences were observed in gait speed or grip strength. Subjective measures of late-life function improved (3.4±4.7 points, p\u3c 0.001). Conclusions A technology-based obesity intervention is feasible and acceptable to older adults with obesity and may lead to weight loss and improved physical function. Clinical trial registration Registered on Clinicaltrials.gov #NCT03104205. Registered on April 7, 2017. First participant enrolled on October 1st, 2018

The Bolocam Galactic Plane Survey IV: 1.1 and 0.35 mm Dust Continuum Emission in the Galactic Center Region

The Bolocam Galactic Plane Survey (BGPS) data for a six square degree region of the Galactic plane containing the Galactic center is analyzed and compared to infrared and radio continuum data. The BGPS 1.1 mm emission consists of clumps interconnected by a network of fainter filaments surrounding cavities, a few of which are filled with diffuse near-IR emission indicating the presence of warm dust or with radio continuum characteristic of HII regions or supernova remnants. New 350 {\mu}m images of the environments of the two brightest regions, Sgr A and B, are presented. Sgr B2 is the brightest mm-emitting clump in the Central Molecular Zone and may be forming the closest analog to a super star cluster in the Galaxy. The Central Molecular Zone (CMZ) contains the highest concentration of mm and sub-mm emitting dense clumps in the Galaxy. Most 1.1 mm features at positive longitudes are seen in silhouette against the 3.6 to 24 {\mu}m background observed by the Spitzer Space Telescope. However, only a few clumps at negative longitudes are seen in absorption, confirming the hypothesis that positive longitude clumps in the CMZ tend to be on the near-side of the Galactic center, consistent with the suspected orientation of the central bar in our Galaxy. Some 1.1 mm cloud surfaces are seen in emission at 8 {\mu}m, presumably due to polycyclic aromatic hydrocarbons (PAHs). A ~0.2\degree (~30 pc) diameter cavity and infrared bubble between l \approx 0.0\degree and 0.2\degree surrounds the Arches and Quintuplet clusters and Sgr A. The bubble contains several clumpy dust filaments that point toward Sgr A\ast; its potential role in their formation is explored. [abstract truncated]Comment: 76 pages, 22 figures, published in ApJ: http://iopscience.iop.org/0004-637X/721/1/137

Ocean and coastal acidification off New England and Nova Scotia

Author Posting. © The Oceanography Society, 2015. This article is posted here by permission of The Oceanography Society for personal use, not for redistribution. The definitive version was published in Oceanography 28, no. 2 (2015): 182-197, doi:10.5670/oceanog.2015.41.New England coastal and adjacent Nova Scotia shelf waters have a reduced buffering capacity because of significant freshwater input, making the region’s waters potentially more vulnerable to coastal acidification. Nutrient loading and heavy precipitation events further acidify the region’s poorly buffered coastal waters. Despite the apparent vulnerability of these waters, and fisheries’ and mariculture’s significant dependence on calcifying species, the community lacks the ability to confidently predict how the region’s ecosystems will respond to continued ocean and coastal acidification. Here, we discuss ocean and coastal acidification processes specific to New England coastal and Nova Scotia shelf waters and review current understanding of the biological consequences most relevant to the region. We also identify key research and monitoring needs to be addressed and highlight existing capacities that should be leveraged to advance a regional understanding of ocean and coastal acidification.This project was supported in part by an appointment to the Internship/Research Participation Program at the Office of Water, US Environmental Protection Agency (EPA), administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and the EPA. JS acknowledges support from NASA grant from NNX14AL84G NASA-CCS

Temporal variability in foraminiferal morphology and geochemistry at the West Antarctic Peninsula: a sediment trap study

The West Antarctic Peninsula (WAP) exhibits strong spatial and temporal oceanographic variability, resulting in highly heterogeneous biological productivity. Calcifying organisms that live in the waters off the WAP respond to temporal and spatial variations in ocean temperature and chemistry. These marine calcifiers are potentially threatened by regional climate change with waters already naturally close to carbonate undersaturation. Future projections of carbonate production in the Southern Ocean are challenging due to the lack of historical data collection and complex, decadal climate variability. Here we present a 6-year-long record of the shell fluxes, morphology and stable isotope variability of the polar planktic foraminifera Neogloboquadrina pachyderma (sensu stricto) from near Palmer Station, Antarctica. This species is fundamental to Southern Ocean planktic carbonate production as it is one of the very few planktic foraminifer species adapted to the marine polar environments. We use these new data to obtain insights into its ecology and to derive a robust assessment of the response of this polar species to environmental change. Morphology and stable isotope composition reveal the presence of different growth stages within this tightly defined species. Inter- and intra-annual variability of foraminiferal flux and size is evident and driven by a combination of environmental forcing parameters, most importantly food availability, temperature and sea ice duration and extent. Foraminiferal growth occurs throughout the austral year and is influenced by environmental change, a large portion of which is driven by the Southern Annular Mode and El Niño–Southern Oscillation. A distinct seasonal production is observed, with the highest shell fluxes during the warmest and most productive months of the year. The sensitivity of calcifying foraminifera to environmental variability in this region, from weeks to decades, has implications both for their response to future climatic change and for their use as palaeoclimate indicators. A longer ice-free season could increase carbonate production in this region at least while carbonate saturation is still high enough to allow for thick tests to grow

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Comprehensive Evaluation of One-Carbon Metabolism Pathway Gene Variants and Renal Cell Cancer Risk

Folate and one-carbon metabolism are linked to cancer risk through their integral role in DNA synthesis and methylation. Variation in one-carbon metabolism genes, particularly MTHFR, has been associated with risk of a number of cancers in epidemiologic studies, but little is known regarding renal cancer.Tag single nucleotide polymorphisms (SNPs) selected to produce high genomic coverage of 13 gene regions of one-carbon metabolism (ALDH1L1, BHMT, CBS, FOLR1, MTHFR, MTR, MTRR, SHMT1, SLC19A1, TYMS) and the closely associated glutathione synthesis pathway (CTH, GGH, GSS) were genotyped for 777 renal cell carcinoma (RCC) cases and 1,035 controls in the Central and Eastern European Renal Cancer case-control study. Associations of individual SNPs (n = 163) with RCC risk were calculated using unconditional logistic regression adjusted for age, sex and study center. Minimum p-value permutation (Min-P) tests were used to identify gene regions associated with risk, and haplotypes were evaluated within these genes.The strongest associations with RCC risk were observed for SLC19A1 (P(min-P) = 0.03) and MTHFR (P(min-P) = 0.13). A haplotype consisting of four SNPs in SLC19A1 (rs12483553, rs2838950, rs2838951, and rs17004785) was associated with a 37% increased risk (p = 0.02), and exploratory stratified analysis suggested the association was only significant among those in the lowest tertile of vegetable intake.To our knowledge, this is the first study to comprehensively examine variation in one-carbon metabolism genes in relation to RCC risk. We identified a novel association with SLC19A1, which is important for transport of folate into cells. Replication in other populations is required to confirm these findings

Post–COVID-19 Conditions Among Children 90 Days After SARS-CoV-2 Infection

IMPORTANCE Little is known about the risk factors for, and the risk of, developing post-COVID-19 conditions (PCCs) among children. OBJECTIVES To estimate the proportion of SARS-CoV-2-positive children with PCCs 90 days after a positive test result, to compare this proportion with SARS-CoV-2-negative children, and to assess factors associated with PCCs. DESIGN, SETTING, AND PARTICIPANTS This prospective cohort study, conducted in 36 emergency departments (EDs) in 8 countries between March 7, 2020, and January 20, 2021, included 1884 SARS-CoV-2-positive children who completed 90-day follow-up; 1686 of these children were frequency matched by hospitalization status, country, and recruitment date with 1701 SARS-CoV-2-negative controls. EXPOSURE SARS-CoV-2 detected via nucleic acid testing. MAIN OUTCOMES AND MEASURES Post-COVID-19 conditions, defined as any persistent, new, or recurrent health problems reported in the 90-day follow-up survey. RESULTS Of 8642 enrolled children, 2368 (27.4%) were SARS-CoV-2 positive, among whom 2365 (99.9%) had index ED visit disposition data available; among the 1884 children (79.7%) who completed follow-up, the median age was 3 years (IQR, 0-10 years) and 994 (52.8%) were boys. A total of 110 SARS-CoV-2-positive children (5.8%; 95% CI, 4.8%-7.0%) reported PCCs, including 44 of 447 children (9.8%; 95% CI, 7.4%-13.0%) hospitalized during the acute illness and 66 of 1437 children (4.6%; 95% CI, 3.6%-5.8%) not hospitalized during the acute illness (difference. 5.3%; 95% CI, 2.5%-8.5%). Among SARS-CoV-2-positive children, the most common symptom was fatigue or weakness (21 [1.1%]). Characteristics associated with reporting at least 1 PCC at 90 days included being hospitalized 48 hours or more compared with no hospitalization (adjusted odds ratio [aOR], 2.67 [95% CI, 1.63-4.38]); having 4 or more symptoms reported at the index ED visit compared with 1 to 3 symptoms (4-6 symptoms: aOR, 2.35 [95% CI, 1.28-4.31]; >= 7 symptoms: aOR, 4.59 [95% CI, 2.50 8.44]); and being 14 years of age or older compared with younger than 1 year (aOR, 2.67 [95% CI, 1.43-4.99]). SARS-CoV-2-positive children were more likely to report PCCs at 90 days compared with those who tested negative, both among those who were not hospitalized (55 of 1295 [4.2%; 95% CI, 3.2%-5.5%] vs 35 of 1321[2.7%; 95% CI, 1.9%-3.7%]; difference, 1.6% [95% CI, 0.2%-3.0%]) and those who were hospitalized (40 of 391[10.2%; 95% CI, 7.4%-13.7%] vs 19 of 380 [5.0%; 95% CI, 3.0%-7.7%]; difference, 5.2% [95% CI, 1.5%-9.1%]). In addition, SARS-CoV-2 positivity was associated with reporting PCCs 90 days after the index ED visit (aOR, 1.63 [95% CI, 1.14-2.35]), specifically systemic health problems (eg, fatigue, weakness, fever; aOR, 2.44 [95% CI, 1.19-5.00]). CONCLUSIONS AND RELEVANCE In this cohort study, SARS-CoV-2 infection was associated with reporting PCCs at 90 days in children. Guidance and follow-up are particularly necessary for hospitalized children who have numerous acute symptoms and are older.This studywas supported by grants from the Canadian Institutes of Health Research (operating grant: COVID-19-clinical management); the Alberta Health Services-University of Calgary-Clinical Research Fund; the Alberta Children's Hospital Research Institute; the COVID-19 Research Accelerator Funding Track (CRAFT) Program at the University of California, Davis; and the Cincinnati Children's Hospital Medical Center Division of Emergency Medicine Small Grants Program. Dr Funk is supported by the University of Calgary Eyes-High PostDoctoral Research Fund. Dr Freedman is supported by the Alberta Children's Hospital Foundation Professorship in Child Health andWellness

Monkeys and Humans Share a Common Computation for Face/Voice Integration

Speech production involves the movement of the mouth and other regions of the face resulting in visual motion cues. These visual cues enhance intelligibility and detection of auditory speech. As such, face-to-face speech is fundamentally a multisensory phenomenon. If speech is fundamentally multisensory, it should be reflected in the evolution of vocal communication: similar behavioral effects should be observed in other primates. Old World monkeys share with humans vocal production biomechanics and communicate face-to-face with vocalizations. It is unknown, however, if they, too, combine faces and voices to enhance their perception of vocalizations. We show that they do: monkeys combine faces and voices in noisy environments to enhance their detection of vocalizations. Their behavior parallels that of humans performing an identical task. We explored what common computational mechanism(s) could explain the pattern of results we observed across species. Standard explanations or models such as the principle of inverse effectiveness and a “race” model failed to account for their behavior patterns. Conversely, a “superposition model”, positing the linear summation of activity patterns in response to visual and auditory components of vocalizations, served as a straightforward but powerful explanatory mechanism for the observed behaviors in both species. As such, it represents a putative homologous mechanism for integrating faces and voices across primates