Socio-economic position and cardiovascular risk in rural Indian adolescents: evidence from the Andhra Pradesh children and parents study (APCAPS).

OBJECTIVES: This study examined association between socio-economic position and cardiovascular risk factors in adolescents to investigate whether childhood socio-economic position is a risk factor for future cardiovascular disease, independently of adult behaviours. STUDY DESIGN AND METHODS: Participants (n = 1128, 46% girls, aged 13-18 years) were members of a birth cohort (Andhra Pradesh Children and Parents Study or APCAPS) established to investigate long-term effects of a pregnancy and childhood nutritional supplementation trial conducted in 29 villages near Hyderabad in South India. Cross-sectional associations between socio-economic position and cardiovascular risk factors were examined using linear regression models. RESULTS: The mean BMI was 16.7 kg/m(2) for boys and 17.8 kg/m(2) for girls. Socio-economic position was positively associated with fat mass index (0.15 kg/m(2); 95% CI: 0.05-0.25) and inversely associated with central-peripheral skinfold ratio (-0.04; 95% CI: -0.06 to -0.01) and, in boys, fasting triglycerides (-0.05; 95% CI: -0.09 to -0.01). Association of socio-economic position with other risk factors (blood pressure, arterial stiffness, fasting glucose, insulin and cholesterol) was weak and inconsistent, and did not persist after adjustment for potential confounders, including age, sex, pubertal stage, height, adiposity and nutrition supplementation. CONCLUSIONS: The study thus showed that lower socio-economic position may be associated with greater central adiposity and higher triglyceride levels in these settings. Socio-economic gradient in cardiovascular risk may strengthen in future with later economic and lifestyle changes. Cardiovascular disease prevention strategies should therefore focus on the youth from the low income group

Postaragonite phases of CaCO3 at lower mantle pressures

The stability, structure and properties of carbonate minerals at lower mantle conditions has significant impact on our understanding of the global carbon cycle and the composition of the interior of the Earth. In recent years, there has been significant interest in the behavior of carbonates at lower mantle conditions, specifically in their carbon hybridization, which has relevance for the storage of carbon within the deep mantle. Using high-pressure synchrotron X-ray diffraction in a diamond anvil cell coupled with direct laser heating of CaCO3 using a CO2 laser, we identify a crystalline phase of the material above 40 GPa − corresponding to a lower mantle depth of around 1,000 km − which has first been predicted by ab initio structure predictions. The observed sp2 carbon hybridized species at 40 GPa is monoclinic with P21/c symmetry and is stable up to 50 GPa, above which it transforms into a structure which cannot be indexed by existing known phases. A combination of ab initio random structure search (AIRSS) and quasi-harmonic approximation (QHA) calculations are used to re-explore the relative phase stabilities of the rich phase diagram of CaCO3. Nudged elastic band (NEB) calculations are used to investigate the reaction mechanisms between relevant crystal phases of CaCO3 and we postulate that the mineral is capable of undergoing sp2-sp3 hybridization change purely in the P21/c structure − forgoing the accepted post-aragonite Pmmn structure

Gender differences in self-reported camouflaging in autistic and non-autistic adults.

Social camouflaging describes the use of strategies to compensate for and mask autistic characteristics during social interactions. A newly developed self-reported measure of camouflaging (Camouflaging Autistic Traits Questionnaire) was used in an online survey to measure gender differences in autistic (n = 306) and non-autistic adults (n = 472) without intellectual disability for the first time. Controlling for age and autistic-like traits, an interaction between gender and diagnostic status was found: autistic females demonstrated higher total camouflaging scores than autistic males (partial η2 = 0.08), but there was no camouflaging gender difference for non-autistic people. Autistic females scored higher than males on two of three Camouflaging Autistic Traits Questionnaire subscales: Masking (partial η2 = 0.05) and Assimilation (partial η2 = 0.06), but not on the Compensation subscale. No differences were found between non-autistic males and females on any subscale. No differences were found between non-binary individuals and other genders in either autistic or non-autistic groups, although samples were underpowered. These findings support previous observations of greater camouflaging in autistic females than males and demonstrate for the first time no self-reported gender difference in non-autistic adults

Comparing [C II], H I, and CO dynamics of nearby galaxies

The HI and CO components of the interstellar medium (ISM) are usually used to derive the dynamical mass M-dyn of nearby galaxies. Both components become too faint to be used as a tracer in observations of high-redshift galaxies. In those cases, the 158 mu m line of atomic carbon ([CII]) may be the only way to derive M-dyn. As the distribution and kinematics of the ISM tracer affects the determination of M-dyn, it is important to quantify the relative distributions of HI, CO, and [CII]. HI and CO are well-characterized observationally, however, for [CII] only very few measurements exist. Here we compare observations of CO, HI, and [CII] emission of a sample of nearby galaxies, drawn from the HERACLES, THINGS, and KINGFISH surveys. We find that within R-25, the average [CII] exponential radial profile is slightly shallower than that of the CO, but much steeper than the HI distribution. This is also reflected in the integrated spectrum ("global profile"), where the [CII] spectrum looks more like that of the CO than that of the HI. For one galaxy, a spectrally resolved comparison of integrated spectra was possible; other comparisons were limited by the intrinsic line-widths of the galaxies and the coarse velocity resolution of the [CII] data. Using high-spectral-resolution SOFIA [CII] data of a number of star forming regions in two nearby galaxies, we find that their [CII] linewidths agree better with those of the CO than the HI. As the radial extent of a given ISM tracer is a key input in deriving M-dyn from spatially unresolved data, we conclude that the relevant length-scale to use in determining M-dyn based on [CII] data, is that of the well-characterized CO distribution. This length scale is similar to that of the optical disk

Impaired allocentric spatial processing in posttraumatic stress disorder.

A neurobiological dual representation model of PTSD proposes that reduced hippocampus-dependent contextual processing contributes to intrusive imagery due to a loss of control over hippocampus-independent sensory and affective representations. We investigated whether PTSD sufferers show impaired allocentric spatial processing indicative of reduced hippocampal functioning. Trauma-exposed individuals with (N=29) and without (N=30) a diagnosis of PTSD completed two tests of spatial processing: a topographical recognition task comprising perceptual and memory components, and a test of memory for objects' locations within a virtual environment in which the test is from either the same viewpoint as presentation (solvable with egocentric memory) or a different viewpoint (requiring allocentric memory). Participants in the PTSD group performed significantly worse on allocentric spatial processing than trauma-exposed controls. Groups performed comparably on egocentric memory and non-spatial memory for lists of objects. Exposure to repeated incident trauma was also associated with significantly worse spatial processing in the PTSD group. Results show a selective impairment in allocentric spatial processing, implicating weak hippocampal functioning, as predicted by a neurobiological dual representation model of PTSD. These findings have important clinical implications for cognitive therapy

Is social camouflaging associated with anxiety and depression in autistic adults?

BACKGROUND: There is inconsistent evidence for a clear pattern of association between 'camouflaging' (strategies used to mask and/or compensate for autism characteristics during social interactions) and mental health. METHODS: This study explored the relationship between self-reported camouflaging and generalised anxiety, depression, and social anxiety in a large sample of autistic adults and, for the first time, explored the moderating effect of gender, in an online survey. RESULTS: Overall, camouflaging was associated with greater symptoms of generalised anxiety, depression, and social anxiety, although only to a small extent beyond the contribution of autistic traits and age. Camouflaging more strongly predicted generalised and social anxiety than depression. No interaction between camouflaging and gender was found. LIMITATIONS: These results cannot be generalised to autistic people with intellectual disability, or autistic children and young people. The sample did not include sufficient numbers of non-binary people to run separate analyses; therefore, it is possible that camouflaging impacts mental health differently in this population. CONCLUSIONS: The findings suggest that camouflaging is a risk factor for mental health problems in autistic adults without intellectual disability, regardless of gender. We also identified levels of camouflaging at which risk of mental health problems is highest, suggesting clinicians should be particularly aware of mental health problems in those who score at or above these levels

Discovery of high affinity inhibitors of Leishmania donovani N-myristoyltransferase

N-Myristoyltransferase (NMT) is a potential drug target in Leishmania parasites. Scaffold-hopping from published inhibitors yielded the serendipitous discovery of a chemotype selective for Leishmania donovani NMT; development led to high affinity inhibitors with excellent ligand efficiency. The binding mode was characterised by crystallography and provides a structural rationale for selectivity

Cohort profile: Andhra Pradesh Children and Parents Study (APCAPS).

The Andhra Pradesh Children and Parents Study (APCAPS) was originally established to study the long-term effects of early-life undernutrition on risk of cardiovascular disease. Its aims were subsequently expanded to include trans-generational influences of other environmental and genetic factors on chronic diseases in rural India. It builds on the Hyderabad Nutrition Trial (HNT) conducted in 1987-90 to compare the effects on birthweight of a protein-calorie supplement for pregnant women and children. The index children of HNT and their mothers were retraced and examined in 2003-05, and the children re-examined as young adults aged 18-21 years in 2009-10. The cohort was expanded to include both parents and siblings of the index children in a recently completed follow-up conducted in 2010-12 (N=∼6225 out of 10,213 participants). Recruitment of the remaining residents of these 29 villages (N=∼55,000) in Ranga Reddy district of Andhra Pradesh is now under way. Extensive data on socio-demographic, lifestyle, medical, anthropometric, physiological, vascular and body composition measures, DNA, stored plasma, and assays of lipids and inflammatory markers on APCAPS participants are available. Details of how to access these data are available from the corresponding author

Effect of integration of supplemental nutrition with public health programmes in pregnancy and early childhood on cardiovascular risk in rural Indian adolescents: long term follow-up of Hyderabad nutrition trial.

OBJECTIVE: To determine whether integration of nutritional supplementation with other public health programmes in early life reduces the risk of cardiovascular disease in undernourished populations. DESIGN: Approximately 15 years' follow-up of participants born within an earlier controlled, community trial of nutritional supplementation integrated with other public health programmes. SETTING: 29 villages (15 intervention, 14 control) near Hyderabad city, south India. PARTICIPANTS: 1165 adolescents aged 13-18 years. INTERVENTION: Balanced protein-calorie supplementation (2.51 MJ, 20 g protein) offered daily to pregnant women and preschool children aged under 6 years, coupled with integrated delivery of vertical public health programmes. MAIN OUTCOME MEASURES: Height, adiposity, blood pressures, lipids, insulin resistance (homoeostasis model assessment (HOMA) score), and arterial stiffness (augmentation index). RESULTS: The participants from the intervention villages were 14 mm (95% confidence interval 4 to 23; P=0.007) taller than controls but had similar body composition. The participants from the intervention villages had more favourable measures of insulin resistance and arterial stiffness: 20% (3% to 39%; P=0.02) lower HOMA score and 3.3% (1% to 5.7%; P=0.008) lower augmentation index. No strong evidence existed for differences in blood pressures and serum lipids. CONCLUSIONS: In this undernourished population, integrated delivery of supplemental nutrition with other public health programmes in pregnancy and early childhood was associated with a more favourable profile of cardiovascular disease risk factors in adolescence. This pragmatic study provides the most robust evidence to date on this important hypothesis for which classic trials are unlikely. Improved maternal and child nutrition may have a role in reducing the burden of cardiovascular disease in low income and middle income countries

Screening the human exome: a comparison of whole genome and whole transcriptome sequencing

BACKGROUND: There is considerable interest in the development of methods to efficiently identify all coding variants present in large sample sets of humans. There are three approaches possible: whole-genome sequencing, whole-exome sequencing using exon capture methods, and RNA-Seq. While whole-genome sequencing is the most complete, it remains sufficiently expensive that cost effective alternatives are important. RESULTS: Here we provide a systematic exploration of how well RNA-Seq can identify human coding variants by comparing variants identified through high coverage whole-genome sequencing to those identified by high coverage RNA-Seq in the same individual. This comparison allowed us to directly evaluate the sensitivity and specificity of RNA-Seq in identifying coding variants, and to evaluate how key parameters such as the degree of coverage and the expression levels of genes interact to influence performance. We find that although only 40% of exonic variants identified by whole genome sequencing were captured using RNA-Seq; this number rose to 81% when concentrating on genes known to be well-expressed in the source tissue. We also find that a high false positive rate can be problematic when working with RNA-Seq data, especially at higher levels of coverage. CONCLUSIONS: We conclude that as long as a tissue relevant to the trait under study is available and suitable quality control screens are implemented, RNA-Seq is a fast and inexpensive alternative approach for finding coding variants in genes with sufficiently high expression levels