Smaller Regional Gray Matter Volume in Homeless African American Cocaine-Dependent Men: A Preliminary Report

Models of addiction include abnormalities in parts of the brain involving executive function/inhibitory control. Although previous studies have reported evidence of structural abnormalities in cocaine-dependent individuals, none have specifically targeted the homeless. The present preliminary study investigated brain structure in such an understudied group, homeless, crack-cocaine-dependent African American men (n = 9), comparing it to that in healthy controls (n = 8). Structural data were analyzed using voxel based morphometry (VBM) and a regions of interest (ROI) analysis. Homeless cocaine-dependent individuals had smaller gray matter volume in dorsolateral prefrontal cortex, anterior cingulate, the cerebellum, insula, and superior temporal gyrus. Most of these areas subserve executive function or inhibitory control. These results are similar to those found in most previous studies of non-homeless cocaine-dependent individuals. Reduced gray matter in executive function/inhibitory control regions of the brain in cocaine-dependent individuals may be a preexisting risk factor for the development of addiction and/or a consequence of drug abuse

A Residue at the Cytoplasmic Entrance of BK-Type Channels Regulating Single-Channel Opening by Its Hydrophobicity

Single large-conductance calcium-activated K+ (BK) channels encoded by the mSlo gene usually have synchronous gating, but a Drosophila dSlo (A2/C2/E2/G5/10) splice variant (dSlo1A) exhibits very flickery openings. To probe this difference in gating, we constructed a mutant I323T. This channel exhibits four subconductance levels similar to those of dSlo1A. Rectification of the single-channel current-voltage relation of I323T decreased as [Ca2+ ]in increased from 10 to 300 μM. Mutagenesis suggests that the hydrophobicity of the residue at the position is important for the wild-type gating; i.e., increasing hydrophobicity prolongs open duration. Molecular dynamics simulation suggests that four hydrophobic pore-lining residues at position 323 of mSlo act cooperatively in a “shutter-like” mechanism gating the permeation of K+ ions. Rate-equilibrium free energy relations analysis shows that the four I323 residues in an mSlo channel have a conformation 65% similar to the closed conformation during gating. Based on these observations, we suggest that the appearance of rectification and substates of BK-type channels arise from a reduction of the cooperativity among these four residues and a lower probability of being open

Distributionally robust L1-estimation in multiple linear regression

Linear regression is one of the most important and widely used techniques in data analysis, for which a key step is the estimation of the unknown parameters. However, it is often carried out under the assumption that the full information of the error distribution is available. This is clearly unrealistic in practice. In this paper, we propose a distributionally robust formulation of L1-estimation (or the least absolute value estimation) problem, where the only knowledge on the error distribution is that it belongs to a well-defined ambiguity set. We then reformulate the estimation problem as a computationally tractable conic optimization problem by using duality theory. Finally, a numerical example is solved as a conic optimization problem to demonstrate the effectiveness of the proposed approach

Early Adverse Events, HPA Activity and Rostral Anterior Cingulate Volume in MDD

Prior studies have independently reported associations between major depressive disorder (MDD), elevated cortisol concentrations, early adverse events and region-specific decreases in grey matter volume, but the relationships among these variables are unclear. In the present study, we sought to evaluate the relationships between grey matter volume, early adverse events and cortisol levels in MDD.Grey matter volume was compared between 19 controls and 19 individuals with MDD using voxel-based morphometry. A history of early adverse events was assessed using the Childhood Trauma Questionnaire. Subjects also provided salivary cortisol samples. Depressed patients showed decreased grey matter volume in the rostral ACC as compared to controls. Rostral ACC volume was inversely correlated with both cortisol and early adverse events.These findings suggest a key relationship between ACC morphology, a history of early adverse events and circulating cortisol in the pathophysiology of MDD

Integrating Functional and Diffusion Magnetic Resonance Imaging for Analysis of Structure-Function Relationship in the Human Language Network

The capabilities of magnetic resonance imaging (MRI) to measure structural and functional connectivity in the human brain have motivated growing interest in characterizing the relationship between these measures in the distributed neural networks of the brain. In this study, we attempted an integration of structural and functional analyses of the human language circuits, including Wernicke's (WA), Broca's (BA) and supplementary motor area (SMA), using a combination of blood oxygen level dependent (BOLD) and diffusion tensor MRI.Functional connectivity was measured by low frequency inter-regional correlations of BOLD MRI signals acquired in a resting steady-state, and structural connectivity was measured by using adaptive fiber tracking with diffusion tensor MRI data. The results showed that different language pathways exhibited different structural and functional connectivity, indicating varying levels of inter-dependence in processing across regions. Along the path between BA and SMA, the fibers tracked generally formed a single bundle and the mean radius of the bundle was positively correlated with functional connectivity. However, fractional anisotropy was found not to be correlated with functional connectivity along paths connecting either BA and SMA or BA and WA. for use in diagnosing and determining disease progression and recovery

What drives residential rooftop solar growth in China? A spatial analysis using city-level data

The growth of Residential rooftop solar (RRS) in some western countries has predominantly been driven by individual or market behaviour and has been extensively studied. However, the development landscape of RRS in China differs, and its driving mechanisms remain unclear. To address this research gap, we investigate the spatial distribution pattern and driving factors of RRS growth using city-level data on RRS installation. Employing the Geographical Detector Model, we calculate indicators to identify the contributions of various socio-economic factors to RRS growth and the strength of their interactions. Our key findings include: 1) significant spatial heterogeneity in RRS growth across regions with different natural and socio-economic characteristics, which impact RRS growth in two patterns: one-way and inverted U-shaped; 2) although solar radiation abundancy is important, air pollution and certain socio-economic factors appear more influential, be it comparing between the eastern and western China, or north and south; 3) the significance of fiscal subsidies has diminished, but benchmark electricity prices (BEP) could serve as a useful alternative; 4) substantial synergistic effects exist between different factors, with environmental and demographic factors displaying particularly strong synergies with others, suggesting that they are essential considerations for future RRS planning. Our findings contribute to a comprehensive understanding of RRS development in China and hold critical implications for future policy design

How can we design a proper trial for vitamin D treatment of diseases? Facts and numbers

Abstract Vitamin D deficiency is a globally common situation and closely related with many chronic diseases. It is a hot topic to examine if vitamin D supplementation is effective for the treatment of diseases, and there have been dozens of clinical trials published in recent years. However, most studies have not proved the extra‐skeletal benefits of vitamin D supplementation on these diseases. Some inherent shortcomings of these trials, such as inclusion with vitamin D‐sufficient and obese participants, low response rate from participants and the insensitive changes in chosen outcomes over a shorter period, may be main reasons why most studies have yet to demonstrate effects of vitamin D supplementation. In this editorial, we aim to discuss the perspectives on how can we design a proper trial for vitamin D treatment of diseases based on the evidence‐based practice framework PICOS (participants, intervention, control, outcomes and study design) in the future. First, right participants should be chosen, which is crucial for the success of vitamin D clinical trials. Participants with vitamin D sufficiency (e.g., baseline 25(OH)D of >50 nmol/L), obesity (e.g., body mass index > 30 kg/m2) and/or high vitamin D response index could be excluded from the trials. Second, intervention with vitamin D in right forms or dosages should be used. Vitamin D3 supplementation with appropriate dosages that keep 25(OH)D levels between 75 and 100 nmol/L is recommended. Third, ‘contamination’ in the control groups needs to pay attention. To diminish this, it is ideal to include participants less interfered by sun exposure (such as living in places at a high latitude) or with greater compliance (less interference by supplemental vitamin D‐containing nutrients). Fourth, the outcome measures should be sensitive to change to avoid type II error. For outcomes such as bone density, radiographic osteoarthritis and cardiovascular diseases, follow‐up period of 3–5 years may be required to observe the changes. Last, precision clinical trials may be the only way to prove the benefits of vitamin D supplementation