Ethnic differences in Glycaemic control in people with type 2 diabetes mellitus living in Scotland

Background and Aims: Previous studies have investigated the association between ethnicity and processes of care and intermediate outcomes of diabetes, but there are limited population-based studies available. The aim of this study was to use population-based data to investigate the relationships between ethnicity and glycaemic control in men and women with diabetes mellitus living in Scotland.<p></p> Methods: We used a 2008 extract from the population-based national electronic diabetes database of Scotland. The association between ethnicity with mean glycaemic control in type 2 diabetes mellitus was examined in a retrospective cohort study, including adjustment for a number of variables including age, sex, socioeconomic status, body mass index (BMI), prescribed treatment and duration of diabetes.<p></p> Results: Complete data for analyses were available for 56,333 White Scottish adults, 2,535 Pakistanis, 857 Indians, 427 Chinese and 223 African-Caribbeans. All other ethnic groups had significantly (p<0.05) greater proportions of people with suboptimal glycaemic control (HbA1c >58 mmol/mol, 7.5%) compared to the White Scottish group, despite generally younger mean age and lower BMI. Fully adjusted odds ratios for suboptimal glycaemic control were significantly higher among Pakistanis and Indians (1.85, 95% CI: 1.68–2.04, and 1.62,95% CI: 1.38–1.89) respectively.<p></p> Conclusions: Pakistanis and Indians with type 2 diabetes mellitus were more likely to have suboptimal glycaemic control than the white Scottish population. Further research on health services and self-management are needed to understand the association between ethnicity and glycaemic control to address ethnic disparities in glycaemic control.<p></p&gt

"Beads on a String" Star Formation Tied to one of the most Powerful AGN Outbursts Observed in a Cool Core Galaxy Cluster

With two central galaxies engaged in a major merger and a remarkable chain of 19 young stellar superclusters wound around them in projection, the galaxy cluster SDSS J1531+3414 ($z=0.335$) offers an excellent laboratory to study the interplay between mergers, AGN feedback, and star formation. New Chandra X-ray imaging reveals rapidly cooling hot ($T\sim 10^6$ K) intracluster gas, with two "wings" forming a concave density discontinuity near the edge of the cool core. LOFAR $144$ MHz observations uncover diffuse radio emission strikingly aligned with the "wings," suggesting that the "wings" are actually the opening to a giant X-ray supercavity. The steep radio emission is likely an ancient relic of one of the most energetic AGN outbursts observed, with $4pV > 10^{61}$ erg. To the north of the supercavity, GMOS detects warm ($T\sim 10^4$ K) ionized gas that enshrouds the stellar superclusters but is redshifted up to $+ 800$ km s$^{-1}$ with respect to the southern central galaxy. ALMA detects a similarly redshifted $\sim 10^{10}$ M$_\odot$ reservoir of cold ($T\sim 10^2$ K) molecular gas, but it is offset from the young stars by $\sim 1{-}3$ kpc. We propose that the multiphase gas originated from low-entropy gas entrained by the X-ray supercavity, attribute the offset between the young stars and the molecular gas to turbulent intracluster gas motions, and suggest that tidal interactions stimulated the "beads on a string" star formation morphology.Comment: Accepted by ApJ, 36 pages, 23 figure

Aetiology of Diarrhoea in a Birth Cohort of Children Aged 0-2 Year(s) in Rural Mirzapur, Bangladesh

The incidence of aetiology-specific diarrhoea and the pathogenicity of infectious agents in a birth cohort (n=252) in rural Bangladesh were determined. Stool specimens or rectal swabs were collected from diarrhoeal cases over two years and routinely on a monthly basis. Stool samples from children with diarrhoea were compared with stool samples from children without diarrhoea to calculate rates of isolation and pathogenicity of agents. In total, 1,750 stool specimens from diarrhoea patients and 5,679 stool specimens from children without diarrhoea were tested. An infectious agent was identified in 58% of the stool specimens from diarrhoea patients and 21.6% of the stool specimens from children without diarrhoea. The most commonly-isolated pathogens from all specimens were enterotoxigenic Escherichia coli (ETEC), enteroadherent E. coli, Shigella , Campylobacter jejuni , Giardia , and rotavirus. ETEC (ST and LT-ST toxin), enterotoxigenic Bacteroides fragilis , Shigella, and rotavirus were associated more with disease than with asymptomatic infections. Aetiology-specific infections were associated with acute episodes. The isolated enteropathogens were essentially the same as those found in other tropical rural settings. Enterotoxigenic B. fragilis was also identified as a pathogen. Ongoing vaccine efforts focusing on Shigella, rotavirus, and ETEC would be useful

Design Considerations for Tumor-Targeted Nanoparticles

Inorganic/organic hybrid nanoparticles are potentially useful in biomedicine, but to avoid non-specific background fluorescence and long-term toxicity, they need to be cleared from the body within a reasonable timescale1. Previously, we have shown that rigid spherical nanoparticles such as quantum dots can be cleared by the kidneys if they have a hydrodynamic diameter of approximately 5.5 nm and a zwitterionic surface charge2. Here, we show that quantum dots functionalized with high-affinity small-molecule ligands that target tumours can also be cleared by the kidneys if their hydrodynamic diameter is less than this value, which sets an upper limit of 5–10 ligands per quantum dot for renal clearance. Animal models of prostate cancer and melanoma show receptor-specific imaging and renal clearance within 4 h post-injection. This study suggests a set of design rules for the clinical translation of targeted nanoparticles that can be eliminated through the kidneys.National Science Foundation (U.S.) (NSF-0070319)National Institutes of Health (U.S.) (NIH GM68762)National Institutes of Health (U.S.) (NIH grant no. R33-EB-000673)National Institutes of Health (U.S.) ( NIH grant no. R01-CA-115296)National Institutes of Health (U.S.) (MIT-Harvard NanoMedical Consortium (1U54-CA119349, a Center of Cancer Nanotechnology Excellence))Bank of AmericaMedical Foundation, inc. (Charles A. King Trust Postdoctoral Research Fellowship Program)cance

Hypothalamic over-expression of VGF in the Siberian hamster increases energy expenditure and reduces body weight gain

VGF (non-acronymic) was first highlighted to have a role in energy homeostasis through experiments involving dietary manipulation in mice. Fasting increased VGF mRNA in the Arc and levels were subsequently reduced upon refeeding. This anabolic role for VGF was supported by observations in a VGF null (VGF-/-) mouse and in the diet-induced and gold-thioglucose obese mice. However, this anabolic role for VGF has not been supported by a number of subsequent studies investigating the physiological effects of VGF-derived peptides. Intracerebroventricular (ICV) infusion of TLQP-21 increased resting energy expenditure and rectal temperature in mice and protected against diet-induced obesity. Similarly, ICV infusion of TLQP-21 into Siberian hamsters significantly reduced body weight, but this was due to a decrease in food intake, with no effect on energy expenditure. Subsequently NERP-2 was shown to increase food intake in rats via the orexin system, suggesting opposing roles for these VGF-derived peptides. Thus to further elucidate the role of hypothalamic VGF in the regulation of energy homeostasis we utilised a recombinant adeno-associated viral vector to over-express VGF in adult male Siberian hamsters, thus avoiding any developmental effects or associated functional compensation. Initially, hypothalamic over-expression of VGF in adult Siberian hamsters produced no effect on metabolic parameters, but by 12 weeks post-infusion hamsters had increased oxygen consumption and a tendency to increased carbon dioxide production; this attenuated body weight gain, reduced interscapular white adipose tissue and resulted in a compensatory increase in food intake. These observed changes in energy expenditure and food intake were associated with an increase in the hypothalamic contents of the VGF-derived peptides AQEE, TLQP and NERP-2. The complex phenotype of the VGF-/- mice is a likely consequence of global ablation of the gene and its derived peptides during development, as well as in the adult

Carbon dioxide and methane measurements from the Los Angeles Megacity Carbon Project – Part 1: calibration, urban enhancements, and uncertainty estimates

We report continuous surface observations of carbon dioxide (CO_2) and methane (CH_4) from the Los Angeles (LA) Megacity Carbon Project during 2015. We devised a calibration strategy, methods for selection of background air masses, calculation of urban enhancements, and a detailed algorithm for estimating uncertainties in urban-scale CO_2 and CH_4 measurements. These methods are essential for understanding carbon fluxes from the LA megacity and other complex urban environments globally. We estimate background mole fractions entering LA using observations from four extra-urban sites including two marine sites located south of LA in La Jolla (LJO) and offshore on San Clemente Island (SCI), one continental site located in Victorville (VIC), in the high desert northeast of LA, and one continental/mid-troposphere site located on Mount Wilson (MWO) in the San Gabriel Mountains. We find that a local marine background can be established to within  ∼  1 ppm CO_2 and  ∼  10 ppb CH_4 using these local measurement sites. Overall, atmospheric carbon dioxide and methane levels are highly variable across Los Angeles. Urban and suburban sites show moderate to large CO_2 and CH_4 enhancements relative to a marine background estimate. The USC (University of Southern California) site near downtown LA exhibits median hourly enhancements of  ∼  20 ppm CO_2 and  ∼  150 ppb CH_4 during 2015 as well as  ∼  15 ppm CO_2 and  ∼  80 ppb CH_4 during mid-afternoon hours (12:00–16:00 LT, local time), which is the typical period of focus for flux inversions. The estimated measurement uncertainty is typically better than 0.1 ppm CO_2 and 1 ppb CH_4 based on the repeated standard gas measurements from the LA sites during the last 2 years, similar to Andrews et al. (2014). The largest component of the measurement uncertainty is due to the single-point calibration method; however, the uncertainty in the background mole fraction is much larger than the measurement uncertainty. The background uncertainty for the marine background estimate is  ∼  10 and  ∼  15 % of the median mid-afternoon enhancement near downtown LA for CO_2 and CH_4, respectively. Overall, analytical and background uncertainties are small relative to the local CO_2 and CH_4 enhancements; however, our results suggest that reducing the uncertainty to less than 5 % of the median mid-afternoon enhancement will require detailed assessment of the impact of meteorology on background conditions

Deep phenotyping and genomic data from a nationally representative study on dementia in India

The Harmonized Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD) is a nationally representative in-depth study of cognitive aging and dementia. We present a publicly available dataset of harmonized cognitive measures of 4,096 adults 60 years of age and older in India, collected across 18 states and union territories. Blood samples were obtained to carry out whole blood and serum-based assays. Results are included in a venous blood specimen datafile that can be linked to the Harmonized LASI-DAD dataset. A global screening array of 960 LASI-DAD respondents is also publicly available for download, in addition to neuroimaging data on 137 LASI-DAD participants. Altogether, these datasets provide comprehensive information on older adults in India that allow researchers to further understand risk factors associated with cognitive impairment and dementia.Peer reviewe

Consensus Recommendation for Mouse Models of Ocular Hypertension to Study Aqueous Humor Outflow and Its Mechanisms.

Due to their similarities in anatomy, physiology, and pharmacology to humans, mice are a valuable model system to study the generation and mechanisms modulating conventional outflow resistance and thus intraocular pressure. In addition, mouse models are critical for understanding the complex nature of conventional outflow homeostasis and dysfunction that results in ocular hypertension. In this review, we describe a set of minimum acceptable standards for developing, characterizing, and utilizing mouse models of open-angle ocular hypertension. We expect that this set of standard practices will increase scientific rigor when using mouse models and will better enable researchers to replicate and build upon previous findings

PDBe: improved findability of macromolecularstructure data in the PDB

© 2019 The Authors. Published by OUP. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1093/nar/gkz990The Protein Data Bank in Europe (PDBe), a founding member of the Worldwide Protein Data Bank (wwPDB), actively participates in the deposition, curation, validation, archiving and dissemination of macromolecular structure data. PDBe supports diverse research communities in their use of macromolecular structures by enriching the PDB data and by providing advanced tools and services for effective data access, visualization and analysis. This paper details the enrichment of data at PDBe, including mapping of RNA structures to Rfam, and identification of molecules that act as cofactors. PDBe has developed an advanced search facility with ∼100 data categories and sequence searches. New features have been included in the LiteMol viewer at PDBe, with updated visualization of carbohydrates and nucleic acids. Small molecules are now mapped more extensively to external databases and their visual representation has been enhanced. These advances help users to more easily find and interpret macromolecular structure data in order to solve scientific problems.The Protein Data Bank in Europe is supported by European Molecular Biology Laboratory-European Bioinformatics Institute; Wellcome Trust [104948]; Biotechnology and Biological Sciences Research Council [BB/N019172/1, BB/G022577/1, BB/J007471/1, BB/K016970/1, BB/K020013/1, BB/M013146/1, BB/M011674/1, BB/M020347/1, BB/M020428/1, BB/P024351/1]; European Union [284209]; ELIXIR and Open Targets. Funding for open access charge: EMB

“Beads-on-a-string” star formation tied to one of the most powerful active galactic nucleus outbursts observed in a cool-core galaxy cluster

With two central galaxies engaged in a major merger and a remarkable chain of 19 young stellar superclusters wound around them in projection, the galaxy cluster SDSS J1531+3414 (z = 0.335) offers an excellent laboratory to study the interplay between mergers, active galactic nucleus (AGN) feedback, and star formation. New Chandra X-ray imaging reveals rapidly cooling hot (T ∼ 106 K) intracluster gas, with two “wings” forming a concave density discontinuity near the edge of the cool core. LOFAR 144 MHz observations uncover diffuse radio emission strikingly aligned with the “wings,” suggesting that the “wings” are actually the opening to a giant X-ray supercavity. The steep radio emission is likely an ancient relic of one of the most energetic AGN outbursts observed, with 4pV > 1061 erg. To the north of the supercavity, GMOS detects warm (T ∼ 104 K) ionized gas that enshrouds the stellar superclusters but is redshifted up to +800 km s−1 with respect to the southern central galaxy. The Atacama Large Millimeter/submillimeter Array detects a similarly redshifted ∼1010 M ⊙ reservoir of cold (T ∼ 102 K) molecular gas, but it is offset from the young stars by ∼1–3 kpc. We propose that the multiphase gas originated from low-entropy gas entrained by the X-ray supercavity, attribute the offset between the young stars and the molecular gas to turbulent intracluster gas motions, and suggest that tidal interactions stimulated the “beads-on-a-string” star formation morphology