Preliminary Evidence That CD38 Moderates the Association of Neuroticism on Amygdala-Subgenual Cingulate Connectivity.

CD38 genetic variation has been associated with autism spectrum disorders and social anxiety disorder, which may result from CD38's regulation of oxytocin secretion. Converging evidence has found that the rs3796863 A-allele contributes to increased social sensitivity compared to the CC genotype. The current study examined the moderating role of CD38 genetic variants (rs3796863 and rs6449182) that have been associated with enhanced (or reduced) social sensitivity on neural activation related to neuroticism, which is commonly elevated in individuals with social anxiety and depression. Adults (n = 72) with varying levels of social anxiety and depression provided biological samples for DNA extraction, completed a measure of neuroticism, and participated in a standardized emotion processing task (affect matching) while undergoing fMRI. A significant interaction effect was found for rs3796863 x neuroticism that predicted right amygdala-subgenual anterior cingulate cortex (sgACC) functional connectivity. Simple slopes analyses showed a positive association between neuroticism and right amygdala-sgACC connectivity among rs3796863 A-allele carriers. Findings suggest that the more socially sensitive rs3796863 A-allele may partially explain the relationship between a known risk factor (i.e. neuroticism) and promising biomarker (i.e. amygdala-sgACC connectivity) in the development and maintenance of social anxiety and depression

The effects of a nutrient supplementation intervention in Ghana on parents’ investments in their children

A child’s endowment is a reflection of his/her genetic makeup and the conditions faced in early life. Parents build on their child’s endowment by investing resources in their child, and together, a child’s endowment and subsequent investments act as input into important later-life outcomes. A positive or negative shock to a child’s endowment can have a direct biological effect on a child’s long-term outcomes but may also affect parents’ decisions about investments in the health and human capital of their children. Using follow-up data collected several years after a randomized trial in Ghana, we explored whether maternal and child supplementation with small-quantity lipid-based nutrient supplements (SQ-LNS) throughout much of the first 1,000 days influenced parental investments in the health and human capital of their children. Across the domains of family planning, breastfeeding, health, education, and paternal financial support, we found that, in general, the intervention did not affect investments in the treated child nor his/her untreated siblings. These results suggest that given production technologies, constraints, and preferences, the intervention either did not change parents’ optimal investment strategies or that the effects of the intervention, namely increased birth size and attained length at 18 months of age, were too small for parents to perceive or to have any meaningful impact on parents’ expectations about the returns to investments in their children

Nomenclature proposal to describe vocal fold motion impairment

The terms used to describe vocal fold motion impairment are confusing and not standardized. This results in a failure to communicate accurately and to major limitations of interpreting research studies involving vocal fold impairment. We propose standard nomenclature for reporting vocal fold impairment. Overarching terms of vocal fold immobility and hypomobility are rigorously defined. This includes assessment techniques and inclusion and exclusion criteria for determining vocal fold immobility and hypomobility. In addition, criteria for use of the following terms have been outlined in detail: vocal fold paralysis, vocal fold paresis, vocal fold immobility/hypomobility associated with mechanical impairment of the crico-arytenoid joint and vocal fold immobility/hypomobility related to laryngeal malignant disease. This represents the first rigorously defined vocal fold motion impairment nomenclature system. This provides detailed definitions to the terms vocal fold paralysis and vocal fold paresis

Modulation of experimental mesangial proliferative nephritis by interferon-γ

Modulation of experimental mesangial proliferative nephritis by interferon-γ. The observation that interferon-γ (IFN-γ) inhibits cell proliferation and collagen synthesis of a variety of cell types in culture has suggested that IFN-γ may be useful in the treatment of fibroproliferative diseases. We administered recombinant IFN-γ subcutaneously (105 U/kg/day for 3 days) to rats, beginning one day after the induction of mesangial proliferative nephritis with anti-Thy 1 antibody. IFN-γ reduced glomerular (primarily mesangial) cell proliferation by 44% at days 2 and 4 compared to vehicle injected control rats with anti-Thy 1 nephritis (that is, proliferating cells that excluded the macrophage marker, ED-1, P < 0.001). Despite the inhibition of mesangial cell proliferation, IFN-γ did not reduce the overall extracellular matrix deposition (by silver stain) or deposition of type IV collagen or laminin (by immunostaining) at 4 or 7 days, and glomerular type IV collagen and laminin mRNA levels were increased (1.4 and 1.7-fold) at 4 days relative to controls. The inability of IFN-γ treatment to reduce mesangial matrix expansion may relate to the fact that IFN-γ treated rats had a twofold increase in glomerular macrophages (that is, ED-1 positive cells, P < 0.001 at 2 and 4 days) with an increase in oxidant producing cells (day 2, P < 0.05) and a 1.6-fold increase in glomerular TGF-β mRNA expression (4 days). This suggests that the effect of IFN-γ to inhibit mesangial cell proliferation in glomerulonephritis may be offset by the ability of IFN-γ to increase glomerular macrophages and TGF-β expression. These data also show that IFN-γ can partly dissociate the mesangial proliferative response from the extracellular matrix expansion in glomerulonephritis

Ghanaian Parents\u27 Perceptions of Pre and Postnatal Nutrient Supplements and their Effects

Small‐quantity lipid‐based nutrient supplements (SQ‐LNS) have been studied in efficacy and effectiveness trials, but little is known about how parents perceive the products and their effects. In a randomised trial in Ghana, efficacy of SQ‐LNS provided to women during pregnancy and the first 6 months postpartum and to their children from 6 to 18 months of age was assessed by comparison with iron‐folic acid (IFA) capsules and multiple micronutrient (MMN) capsules provided to women. In a follow‐up study conducted when the index children from the original trial were between 4 and 6 years of age, we used survey‐based methods to assess retrospective and current parental perceptions of nutrient supplements generally and of SQ‐LNS and their effects compared with perceptions IFA and MMN capsules. Most parents perceived that the assigned supplements (SQ‐LNS, IFA, or MMN) positively impacted the mother during pregnancy (approximately 89% of both mothers and fathers) and during lactation (84% of mothers and 86% of fathers). Almost all (≥90%) of mothers and fathers perceived that the assigned supplement positively impacted the index child and expected continued positive impacts on the child\u27s health and human capital into the future. A smaller percentage of parents perceived negative impacts of the supplements (7%–17% of mothers and 4%–12% of fathers). Perceptions of positive impacts and of negative impacts did not differ by intervention group. The results suggest that similar populations would likely be receptive to programs to deliver SQ‐LNS or micronutrient capsules

The Southern Proper Motion Program IV. The SPM4 Catalog

We present the fourth installment of the Yale/San Juan Southern Proper Motion Catalog, SPM4. The SPM4 contains absolute proper motions, celestial coordinates, and (B,V) photometry for over 103 million stars and galaxies between the south celestial pole and -20 deg declination. The catalog is roughly complete to V=17.5 and is based on photographic and CCD observations taken with the Yale Southern Observatory's double-astrograph at Cesco Observatory in El Leoncito, Argentina. The proper-motion precision, for well-measured stars, is estimated to be 2 to 3 mas/yr, depending on the type of second-epoch material. At the bright end, proper motions are on the International Celestial Reference System by way of Hipparcos Catalog stars, while the faint end is anchored to the inertial system using external galaxies. Systematic uncertainties in the absolute proper motions are on the order of 1 mas/yr.Comment: 34 pages, 8 figures, 3 tables; accepted for publication in AJ; note - modified author list and acknowledgements sectio

Treatment effect heterogeneity following type 2 diabetes treatment with GLP1-receptor agonists and SGLT2-inhibitors:a systematic review

Background: A precision medicine approach in type 2 diabetes requires the identification of clinical and biological features that are reproducibly associated with differences in clinical outcomes with specific anti-hyperglycaemic therapies. Robust evidence of such treatment effect heterogeneity could support more individualized clinical decisions on optimal type 2 diabetes therapy.Methods: We performed a pre-registered systematic review of meta-analysis studies, randomized control trials, and observational studies evaluating clinical and biological features associated with heterogenous treatment effects for SGLT2-inhibitor and GLP1-receptor agonist therapies, considering glycaemic, cardiovascular, and renal outcomes. After screening 5,686 studies, we included 101 studies of SGLT2-inhibitors and 75 studies of GLP1-receptor agonists in the final systematic review.Results: Here we show that the majority of included papers have methodological limitations precluding robust assessment of treatment effect heterogeneity. For SGLT2-inhibitors, multiple observational studies suggest lower renal function as a predictor of lesser glycaemic response, while markers of reduced insulin secretion predict lesser glycaemic response with GLP1-receptor agonists. For both therapies, multiple post-hoc analyses of randomized control trials (including trial meta-analysis) identify minimal clinically relevant treatment effect heterogeneity for cardiovascular and renal outcomes.Conclusions: Current evidence on treatment effect heterogeneity for SGLT2-inhibitor and GLP1-receptor agonist therapies is limited, likely reflecting the methodological limitations of published studies. Robust and appropriately powered studies are required to understand type 2 diabetes treatment effect heterogeneity and evaluate the potential for precision medicine to inform future clinical care.</p

Development of a treatment selection algorithm for SGLT2 and DPP-4 inhibitor therapies in people with type 2 diabetes:a retrospective cohort study

Background: Current treatment guidelines do not provide recommendations to support the selection of treatment for most people with type 2 diabetes. We aimed to develop and validate an algorithm to allow selection of optimal treatment based on glycaemic response, weight change, and tolerability outcomes when choosing between SGLT2 inhibitor or DPP-4 inhibitor therapies. Methods: In this retrospective cohort study, we identified patients initiating SGLT2 and DPP-4 inhibitor therapies after Jan 1, 2013, from the UK Clinical Practice Research Datalink (CPRD). We excluded those who received SGLT2 or DPP-4 inhibitors as first-line treatment or insulin at the same time, had estimated glomerular filtration rate (eGFR) of less than 45 mL/min per 1·73 m2, or did not have a valid baseline glycated haemoglobin (HbA1c) measure (&lt;53 or ≥120 mmol/mol). The primary efficacy outcome was the HbA1c value reached 6 months after drug initiation, adjusted for baseline HbA1c. Clinical features associated with differential HbA1c outcome on the two therapies were identified in CPRD (n=26 877), and replicated in reanalysis of 14 clinical trials (n=10 414). An algorithm to predict individual-level differential HbA1c outcome on the two therapies was developed in CPRD (derivation; n=14 069) and validated in head-to-head trials (n=2499) and CPRD (independent validation; n=9376). In CPRD, we further explored heterogeneity in 6-month weight change and treatment discontinuation. Findings: Among 10 253 patients initiating SGLT2 inhibitors and 16 624 patients initiating DPP-4 inhibitors in CPRD, baseline HbA1c, age, BMI, eGFR, and alanine aminotransferase were associated with differential HbA1c outcome with SGLT2 inhibitor and DPP-4 inhibitor therapies. The median age of participants was 62·0 years (IQR 55·0–70·0). 10 016 (37·3%) were women and 16 861 (62·7%) were men. An algorithm based on these five features identified a subgroup, representing around four in ten CPRD patients, with a 5 mmol/mol or greater observed benefit with SGLT2 inhibitors in all validation cohorts (CPRD 8·8 mmol/mol [95% CI 7·8–9·8]; CANTATA-D and CANTATA-D2 trials 5·8 mmol/mol [3·9–7·7]; BI1245.20 trial 6·6 mmol/mol [2·2–11·0]). In CPRD, predicted differential HbA1c response with SGLT2 inhibitor and DPP-4 inhibitor therapies was not associated with weight change. Overall treatment discontinuation within 6 months was similar in patients predicted to have an HbA1c benefit with SGLT2 inhibitors over DPP-4 inhibitors (median 15·2% [13·2–20·3] vs 14·4% [12·9–16·7]). A smaller subgroup predicted to have greater HbA1c reduction with DPP-4 inhibitors were twice as likely to discontinue SGLT2 inhibitors than DPP-4 inhibitors (median 26·8% [23·4–31·0] vs 14·8% [12·9–16·8]). Interpretation: A validated treatment selection algorithm for SGLT2 inhibitor and DPP-4 inhibitor therapies can support decisions on optimal treatment for people with type 2 diabetes. Funding: BHF-Turing Cardiovascular Data Science Award and the UK Medical Research Council

The weed community affects yield and quality of soybean (Glycine max (L.) Merr.)

The relationship between the weed community and soybean (Glycine max (L.) Merr.) seed yield and quality was assessed in two soybean experiments in Illinois, USA. One field was sown with different proportions of target weeds (Ambrosia trifida L., Amaranthus rudis J. Sauer, Setaria faberi F. Herrm), and the other was naturally infested with these and other weeds. The composition of the weed communities in both fields were compared to final yield and quality (% protein, oil, and water) of the crop using NMDS ordination. Biomass and canopy cover, and seed quality (% protein, relative water content, seed weight) of the crop, were related to the multivariate structure of the weed community in both experiments. Lower quality soybeans were harvested from plots dominated by the target weeds and a suite of subordinate volunteers. Analysis restricted to the volunteer weed community was also significantly related to seed protein and seed weight. Similar results from the two experiments lend generality to the findings and indicate that soybean producers need to manage the composition of the weed community