Electroconvulsive therapy mediates neuroplasticity of white matter microstructure in major depression.

Whether plasticity of white matter (WM) microstructure relates to therapeutic response in major depressive disorder (MDD) remains uncertain. We examined diffusion tensor imaging (DTI) correlates of WM structural connectivity in patients receiving electroconvulsive therapy (ECT), a rapidly acting treatment for severe MDD. Tract-Based Spatial Statistics (TBSS) applied to DTI data (61 directions, 2.5 mm(3) voxel size) targeted voxel-level changes in fractional anisotropy (FA), and radial (RD), axial (AD) and mean diffusivity (MD) in major WM pathways in MDD patients (n=20, mean age: 41.15 years, 10.32 s.d.) scanned before ECT, after their second ECT and at transition to maintenance therapy. Comparisons made at baseline with demographically similar controls (n=28, mean age: 39.42 years, 12.20 s.d.) established effects of diagnosis. Controls were imaged twice to estimate scanning-related variance. Patients showed significant increases of FA in dorsal fronto-limbic circuits encompassing the anterior cingulum, forceps minor and left superior longitudinal fasciculus between baseline and transition to maintenance therapy (P<0.05, corrected). Decreases in RD and MD were observed in overlapping regions and the anterior thalamic radiation (P<0.05, corrected). Changes in DTI metrics associated with therapeutic response in tracts showing significant ECT effects differed between patients and controls. All measures remained stable across time in controls. Altered WM microstructure in pathways connecting frontal and limbic areas occur in MDD, are modulated by ECT and relate to therapeutic response. Increased FA together with decreased MD and RD, which trend towards normative values with treatment, suggest increased fiber integrity in dorsal fronto-limbic pathways involved in mood regulation

Big Data solutions on a small scale: Evaluating accessible high-performance computing for social research

Though full of promise, Big Data research success is often contingent on access to the newest, most advanced, and often expensive hardware systems and the expertise needed to build and implement such systems. As a result, the accessibility of the growing number of Big Data-capable technology solutions has often been the preserve of business analytics. Pay as you store/process services like Amazon Web Services have opened up possibilities for smaller scale Big Data projects. There is high demand for this type of research in the digital humanities and digital sociology, for example. However, scholars are increasingly finding themselves at a disadvantage as available data sets of interest continue to grow in size and complexity. Without a large amount of funding or the ability to form interdisciplinary partnerships, only a select few find themselves in the position to successfully engage Big Data. This article identifies several notable and popular Big Data technologies typically implemented using large and extremely powerful cloud-based systems and investigates the feasibility and utility of development of Big Data analytics systems implemented using low-cost commodity hardware in basic and easily maintainable configurations for use within academic social research. Through our investigation and experimental case study (in the growing field of social Twitter analytics), we found that not only are solutions like Cloudera’s Hadoop feasible, but that they can also enable robust, deep, and fruitful research outcomes in a variety of use-case scenarios across the disciplines

Tuberculosis and Indoor Biomass and Kerosene Use in Nepal: A Case–Control Study

BackgroundIn Nepal, tuberculosis (TB) is a major problem. Worldwide, six previous epidemiologic studies have investigated whether indoor cooking with biomass fuel such as wood or agricultural wastes is associated with TB with inconsistent results.ObjectivesUsing detailed information on potential confounders, we investigated the associations between TB and the use of biomass and kerosene fuels.MethodsA hospital-based case-control study was conducted in Pokhara, Nepal. Cases (n = 125) were women, 20-65 years old, with a confirmed diagnosis of TB. Age-matched controls (n = 250) were female patients without TB. Detailed exposure histories were collected with a standardized questionnaire.ResultsCompared with using a clean-burning fuel stove (liquefied petroleum gas, biogas), the adjusted odds ratio (OR) for using a biomass-fuel stove was 1.21 [95% confidence interval (CI), 0.48-3.05], whereas use of a kerosene-fuel stove had an OR of 3.36 (95% CI, 1.01-11.22). The OR for use of biomass fuel for heating was 3.45 (95% CI, 1.44-8.27) and for use of kerosene lamps for lighting was 9.43 (95% CI, 1.45-61.32).ConclusionsThis study provides evidence that the use of indoor biomass fuel, particularly as a source of heating, is associated with TB in women. It also provides the first evidence that using kerosene stoves and wick lamps is associated with TB. These associations require confirmation in other studies. If using kerosene lamps is a risk factor for TB, it would provide strong justification for promoting clean lighting sources, such as solar lamps

A systematic analysis of host factors reveals a Med23-interferon-λ regulatory axis against herpes simplex virus type 1 replication

Herpes simplex virus type 1 (HSV-1) is a neurotropic virus causing vesicular oral or genital skin lesions, meningitis and other diseases particularly harmful in immunocompromised individuals. To comprehensively investigate the complex interaction between HSV-1 and its host we combined two genome-scale screens for host factors (HFs) involved in virus replication. A yeast two-hybrid screen for protein interactions and a RNA interference (RNAi) screen with a druggable genome small interfering RNA (siRNA) library confirmed existing and identified novel HFs which functionally influence HSV-1 infection. Bioinformatic analyses found the 358 HFs were enriched for several pathways and multi-protein complexes. Of particular interest was the identification of Med23 as a strongly anti-viral component of the largely pro-viral Mediator complex, which links specific transcription factors to RNA polymerase II. The anti-viral effect of Med23 on HSV-1 replication was confirmed in gain-of-function gene overexpression experiments, and this inhibitory effect was specific to HSV-1, as a range of other viruses including Vaccinia virus and Semliki Forest virus were unaffected by Med23 depletion. We found Med23 significantly upregulated expression of the type III interferon family (IFN-λ) at the mRNA and protein level by directly interacting with the transcription factor IRF7. The synergistic effect of Med23 and IRF7 on IFN-λ induction suggests this is the major transcription factor for IFN-λ expression. Genotypic analysis of patients suffering recurrent orofacial HSV-1 outbreaks, previously shown to be deficient in IFN-λ secretion, found a significant correlation with a single nucleotide polymorphism in the IFN-λ3 (IL28b) promoter strongly linked to Hepatitis C disease and treatment outcome. This paper describes a link between Med23 and IFN-λ, provides evidence for the crucial role of IFN-λ in HSV-1 immune control, and highlights the power of integrative genome-scale approaches to identify HFs critical for disease progression and outcome

The quality and diagnostic value of open narratives in verbal autopsy: a mixed-methods analysis of partnered interviews from Malawi

Background Verbal autopsy (VA), the process of interviewing a deceased’s family or caregiver about signs and symptoms leading up to death, employs tools that ask a series of closed questions and can include an open narrative where respondents give an unprompted account of events preceding death. The extent to which an individual interviewer, who generally does not interpret the data, affects the quality of this data, and therefore the assigned cause of death, is poorly documented. We aimed to examine inter-interviewer reliability of open narrative and closed question data gathered during VA interviews. Methods During the introduction of VA data collection, as part of a larger study in Mchinji district, Malawi, we conducted partner interviews whereby two interviewers independently recorded open narrative and closed questions during the same interview. Closed questions were collected using a smartphone application (mobile-InterVA) and open narratives using pen and paper. We used mixed methods of analysis to evaluate the differences between recorded responses to open narratives and closed questions, causes of death assigned, and additional information gathered by open narrative. Results Eighteen partner interviews were conducted, with complete data for 11 pairs. Comparing closed questions between interviewers, the median number of differences was 1 (IQR: 0.5–3.5) of an average 65 answered; mean inter-interviewer concordance was 92 % (IQR: 92–99 %). Discrepancies in open narratives were summarized in five categories: demographics, history and care-seeking, diagnoses and symptoms, treatment and cultural. Most discrepancies were seen in the reporting of diagnoses and symptoms (e.g., malaria diagnosis); only one pair demonstrated no clear differences. The average number of clinical symptoms reported was 9 in open narratives and 20 in the closed questions. Open narratives contained additional information on health seeking and social issues surrounding deaths, which closed questions did not gather. Conclusions The information gleaned during open narratives was subject to inter-interviewer variability and contained a limited number of symptom indicators, suggesting that their use for assigning cause of death is questionable. However, they contained rich information on care-seeking, healthcare provision and social factors in the lead-up to death, which may be a valuable source of information for promoting accountable health services