General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT ...consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10
) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.
The High Altitude Water Cherenkov (HAWC) collaboration recently published their 2HWC catalog, listing 39 very high energy (VHE; >100 GeV) gamma-ray sources based on 507 days of observation. Among ...these, 19 sources are not associated with previously known teraelectronvolt (TeV) gamma-ray sources. We have studied 14 of these sources without known counterparts with VERITAS and Fermi-LAT. VERITAS detected weak gamma-ray emission in the 1 TeV-30 TeV band in the region of DA 495, a pulsar wind nebula coinciding with 2HWC J1953+294, confirming the discovery of the source by HAWC. We did not find any counterpart for the selected 14 new HAWC sources from our analysis of Fermi-LAT data for energies higher than 10 GeV. During the search, we detected gigaelectronvolt (GeV) gamma-ray emission coincident with a known TeV pulsar wind nebula, SNR G54.1+0.3 (VER J1930+188), and a 2HWC source, 2HWC J1930+188. The fluxes for isolated, steady sources in the 2HWC catalog are generally in good agreement with those measured by imaging atmospheric Cherenkov telescopes. However, the VERITAS fluxes for SNR G54.1+0.3, DA 495, and TeV J2032+4130 are lower than those measured by HAWC, and several new HAWC sources are not detected by VERITAS. This is likely due to a change in spectral shape, source extension, or the influence of diffuse emission in the source region.
Human microbiomes assemble in an ordered, reproducible manner yet there is limited information about early colonisation and development of bacterial communities that constitute the oral microbiome.
...The aim of this study was to determine the effect of exposure to breastmilk on assembly of the infant oral microbiome during the first 20 months of life.
The oral microbiomes of 39 infants, 13 who were never breastfed and 26 who were breastfed for more than 10 months, from the longitudinal VicGeneration birth cohort study, were determined at four ages. In total, 519 bacterial taxa were identified and quantified in saliva by sequencing the V4 region of the bacterial 16S rRNA genes.
There were significant differences in the development of the oral microbiomes of never breastfed and breastfed infants. Bacterial diversity was significantly higher in never breastfed infants at 2 months, due largely to an increased abundance of Veillonella and species from the Bacteroidetes phylum compared with breastfed infants.
These differences likely reflect breastmilk playing a prebiotic role in selection of early-colonising, health-associated oral bacteria, such as the Streptococcus mitis group. The microbiomes of both groups became more heterogenous following the introduction of solid foods.
Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) down-regulates angiotensin-converting enzyme 2, potentially increasing angiotensin II. We hypothesized that losartan ...compared to usual care decreases mortality and is safe in patients hospitalized with coronavirus disease 2019 (COVID-19). We aimed to evaluate the effect of losartan versus usual care on 28-day mortality in patients hospitalized for acute COVID-19. Methods Eligibility criteria included adults admitted for acute COVID-19. Exclusion criteria were hypotension, hyperkalemia, acute kidney injury, and use of angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors within 7 days. Participants were randomized to losartan 25–100 mg/day orally for the hospital duration or 3 months or the control arm (usual care) in 29 hospitals in Canada and France. The primary outcome was 28-day mortality. Secondary outcomes were hospital mortality, organ support, and serious adverse events (SAEs). Results The trial was stopped early because of a serious safety concern with losartan. In 341 patients, any SAE and hypotension were significantly higher in the losartan versus usual care groups (any SAE: 39.8% vs 27.2%, respectively, P = .01; hypotension: 30.4% vs 15.3%, respectively, P < .001) in both ward and intensive care patients. The 28-day mortality did not differ between losartan (6.5%) versus usual care (5.9%) (odds ratio, 1.11 95% confidence interval, .47–2.64; P = .81), nor did organ dysfunction or secondary outcomes. Conclusions Caution is needed in deciding which patients to start or continue using ARBs in patients hospitalized with pneumonia to mitigate risk of hypotension, acute kidney injury, and other side effects. ARBs should not be added to care of patients hospitalized for acute COVID-19. Clinical Trials Registration NCT04606563.
Oesophagogastric adenocarcinomas (OAC) are obesity-associated malignancies, underpinned by severe immune dysregulation. We have previously shown that natural killer (NK) cells preferentially migrate ...to OAC omentum, where they undergo phenotypic and functional alterations and apoptosis. Furthermore, we have identified the CX3CR1:fractalkine (CX3CL1) pathway as pivotal in their recruitment to omentum. Here, we elucidate whether exposure to the soluble microenvironment of OAC omentum, and in particular fractalkine and IL-15 affects NK cell homing capacity towards oesophageal tumour. Our data uncover diminished NK cell migration towards OAC tumour tissue conditioned media (TCM) following exposure to omental adipose tissue conditioned media (ACM) and reveal that this migration can be rescued with CX3CR1 antagonist E6130. Furthermore, we show that fractalkine has opposing effects on NK cell migration towards TCM, when used alone or in combination with IL-15 and uncover its inhibitory effects on IL-15-mediated stimulation of death receptor ligand expression. Interestingly, treatment with fractalkine and/or IL-15 do not significantly affect NK cell adhesion to MAdCAM-1, despite changes they elicit to the expression of integrin α4β7. This study provides further evidence that CX3CR1 antagonism has therapeutic utility in rescuing NK cells from the deleterious effects of the omentum and fractalkine in OAC, thus limiting their dysfunction.
We have conducted a survey of 328 protostars in the Orion molecular clouds with the Atacama Large Millimeter/submillimeter Array at 0.87 mm at a resolution of ∼0 1 (40 au), including observations ...with the Very Large Array at 9 mm toward 148 protostars at a resolution of ∼0 08 (32 au). This is the largest multiwavelength survey of protostars at this resolution by an order of magnitude. We use the dust continuum emission at 0.87 and 9 mm to measure the dust disk radii and masses toward the Class 0, Class I, and flat-spectrum protostars, characterizing the evolution of these disk properties in the protostellar phase. The mean dust disk radii for the Class 0, Class I, and flat-spectrum protostars are , , and au, respectively, and the mean protostellar dust disk masses are 25.9 , , , respectively. The decrease in dust disk masses is expected from disk evolution and accretion, but the decrease in disk radii may point to the initial conditions of star formation not leading to the systematic growth of disk radii or that radial drift is keeping the dust disk sizes small. At least 146 protostellar disks (35% of 379 detected 0.87 mm continuum sources plus 42 nondetections) have disk radii greater than 50 au in our sample. These properties are not found to vary significantly between different regions within Orion. The protostellar dust disk mass distributions are systematically larger than those of Class II disks by a factor of >4, providing evidence that the cores of giant planets may need to at least begin their formation during the protostellar phase.
The use of self expandable metal stents in the palliation of malignant dysphagia and oesophago-respiratory fistulae has increased in recent years. The aim of this study was to report a comprehensive ...4 year audit of a Specialist Unit's experience with the expandable stent. 200 expandable metal stents were deployed for palliation of non operable malignant dysphagia or fistulae. Per-operative, early (<30 days) and late (>30 days) complications specific to the stent were documented. Stents were successfully positioned in all patients. There was no mortality associated with the insertion and no perforation. Dysphagia was palliated initially in 93 per cent of cases. The mean dysphagia score improved significantly from 3.2 to 1.5 (p<0.01). This significant benefit persisted at 3 months and 6 months of follow-up. The commonest complication was stent migration (5.5%) and 23 patients (11%) required a second stent insertion. Oesophago-respiratory fistulae were successfully palliated in all cases. This study demonstrates the effectiveness of self expandable metallic stents in the palliation of non operable malignant dysphagia and oesophago-respiratory fistulae. The minimal risk of significant complications and low incidence of reintervention should establish this approach as first line palliation in these patients.
In 1987, the University of Guelph established a large tree-based intercropping system on 30
ha of prime agricultural land in southern Ontario, Canada. The purpose was to investigate various aspects ...of intercropping trees with prime agricultural crops. In this study, objectives were to investigate tree competitive effects (i.e., shading and competition for soil moisture) on under-story crop net assimilation (NA), growth, and yield. The effects of tree competition on corn (C4 plant) and soybean (C3 plant) photosynthesis and productivity in the intercropped system were studied during the 1997 and 1998 growing seasons. Corn and soybeans were intercropped with hybrid poplar (
clone-DN-177) and silver maple (
Acer sacharrinum) at a within-row spacing of 6 m and between-row spacing of 12.5 or 15
m. Trees were absent from control rows. Tree rows were oriented approximately north and south. Twelve crop locations were sampled around each tree. These were at 2 and 6
m east and west of the tree, located along a primary axis running through the tree trunk and perpendicular to the tree row, and at 2
m north and south of each location along the primary axis. Net assimilation and plant water deficit measurements were made three times daily (morning, noon, afternoon) on sampling days in July. Generally, tree competition significantly reduced photosynthetic radiation (PAR), net assimilation (NA), and growth and yield of individual soybean or corn plants growing nearer (2
m) to tree rows in both years and soil moisture in 1998. NA was highly correlated with growth and yield of both crops. These correlations were higher for corn than soybeans in both years, with corn, rather than soybeans being more adversely impacted by tree shading. In 1997, poplar, rather than maple, had the greatest competitive effect on NA. In 1997, the lowest plant water deficits, for soybeans and for corn, were observed for the maple treatment. Nonetheless, in both years, daily plant water deficits were non-significantly and poorly correlated with NA and growth and yield of both crops. However, soil moisture (5 and 15
cm depth) was significantly correlated with soybeans yield in 1998. Possible remediation strategies are discussed to reduce tree competitive interactions on agricultural crops.
•Alcohol use is adversely associated with viral suppression (VS).•Antiretroviral therapy mediates the relationship between alcohol use and VS.•Associations between alcohol use and VS differ by ...gender.
Alcohol use is common among persons living with HIV (PWH) in Uganda and associated with poor HIV care outcomes; findings regarding the relationship between alcohol use and viral suppression (VS) have been inconclusive.
Data from two rounds (2017–2020) of the Rakai Community Cohort Study, an open population-based cohort study in the Rakai region, Uganda, were analyzed. Two alcohol exposures were explored: past year alcohol use and alcohol-related consequences. Multivariable models (GEE) were used to estimate associations between alcohol exposures and VS for the overall sample and stratified by sex, adjusting for repeated measurement. Causal mediation by ART use was explored.
Over half (55 %) of participants (n = 3823 PWH) reported alcohol use at baseline; 37.8 % of those reporting alcohol use reported alcohol-related consequences. ART use and VS at baseline significantly differed by alcohol use with person reporting alcohol use being less likely to be on ART or VS. Alcohol use was significantly associated with decreased odds of VS among women but not men (adj. OR 0.72 95 % CI 0.58−0.89, p = 0.0031). However, among males who use alcohol, experiencing alcohol-related consequences was significantly associated with decreased odds of VS (adj. OR 0.69 95 % CI 0.54−0.88, p = 0.0034). The relationships between both alcohol exposures and VS were not significant in models restricted to persons on ART.
We provide sex-stratified estimates of associations between two alcohol measures and VS in the context of current HIV treatment guidelines. This study confirms that alcohol use is adversely associated with VS but ART use mediates this pathway, suggesting that initiation and retention on ART are critical steps to addressing alcohol-related disparities in VS.
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