Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression

The hypothesis that the S allele of the 5-HTTLPR serotonin transporter promoter region is associated with increased risk of depression, but only in individuals exposed to stressful situations, has generated much interest, research, and controversy since first proposed in 2003. Multiple meta-analyses combining results from heterogeneous analyses have not settled the issue. To determine the magnitude of the interaction and the conditions under which it might be observed, we performed new analyses on 31 datasets containing 38 802 European-ancestry subjects genotyped for 5-HTTLPR and assessed for depression and childhood maltreatment or other stressful life events, and meta-analyzed the results. Analyses targeted two stressors (narrow, broad) and two depression outcomes (current, lifetime). All groups that published on this topic prior to the initiation of our study and met the assessment and sample size criteria were invited to participate. Additional groups, identified by consortium members or self-identified in response to our protocol (published prior to the start of analysis1) with qualifying unpublished data were also invited to participate. A uniform data analysis script implementing the protocol was executed by each of the consortium members. Our findings do not support the interaction hypothesis. We found no subgroups or variable definitions for which an interaction between stress and 5-HTTLPR genotype was statistically significant. In contrast, our findings for the main effects of life stressors (strong risk factor) and 5-HTTLPR genotype (no impact on risk) are strikingly consistent across our contributing studies, the original study reporting the interaction, and subsequent meta-analyses. Our conclusion is that if an interaction exists in which the S allele of 5-HTTLPR increases risk of depression only in stressed individuals, then it is not broadly generalizable, but must be of modest effect size and only observable in limited situations

A Roadmap for HEP Software and Computing R&D for the 2020s

Particle physics has an ambitious and broad experimental programme for the coming decades. This programme requires large investments in detector hardware, either to build new facilities and experiments, or to upgrade existing ones. Similarly, it requires commensurate investment in the R&D of software to acquire, manage, process, and analyse the shear amounts of data to be recorded. In planning for the HL-LHC in particular, it is critical that all of the collaborating stakeholders agree on the software goals and priorities, and that the efforts complement each other. In this spirit, this white paper describes the R&D activities required to prepare for this software upgrade.Peer reviewe

Alterations in respiratory status: Early signs of severe necrotizing enterocolitis

Background: Necrotizing enterocolitis (NEC) presents with well- recognized signs of intestinal inflammation such as bilious vomiting, bloody stool, abdominal distension, and tenderness. The authors observed otherwise unexplained changes in the respiratory status requiring increased respiratory support during the 24 hours before direct evidence of the intestinal, disorder in-patients with severe NEC. Methods: To study this observation the authors collected data on 10 consecutive patients in whom NEC required an operation. Results: Eight of these patients were recovering from respiratory distress syndrome (RDS). During the 24 hours before any direct sign of intestinal dysfunction seven of these eight had 8 respiratory prodrome needing increased respiratory support. Two patients required intubation and mechanical ventilation. Five needed increased supplemental oxygen. This prodrome included decreased oxygenation in seven, increased respiratory rate in five, and increased Pco2 in five, preceded by Conclusions: These changes in the respiratory condition revisit the concept of high output respiratory failure. This term was introduced to describe the respiratory failure in adult patients who suffer acute intestinal illness. Increased metabolic demand from the intestinal illness was thought to stress the ability of the patient to delivery oxygen and remove carbon dioxide. The ability of the respiratory system to meet the increased demands is limited by the intestinal dysfunction itself (abdominal pain and distension). In our patients recovering from RDS the pulmonary reserve is inherently limited. Because they are carefully monitored, it is easy to retrieve evidence of respiratory changes that precede the direct signs of intestinal disease. In the earliest stages of intestinal illness before the direct signs of intestinal dysfunction, these patients often manifest unexplained signs of respiratory compensation and decompensation and require increased respiratory support. Regardless of the pathophysiology, these alterations in respiratory status represent an early warning sign of NEC

Summary of bacterial strains and plasmids used in this work.

<p>Emr, erythromycin resistant; Ampr, ampicillin resistant.</p

Dynamic distribution of Lactobacillus in the GI tract of neonatal rats.

<p>Neonatal rats were fed with <i>L. casei</i> expressing mRFP1. Animals were sacrificed on Days 1, 2, 3 and 4 after gavage. The gastrointestinal homogenates were diluted and plated on MRS plate in the presence of erythromycin. Control rats were fed with saline only. Homogenates from experimental groups were plated on the left half of each plate and those from controls on the right half (A–C). Colonies were found in animals fed with labeled bacteria on Day 1. A) Stomach; B) cecum; C) colon. Scale bars, 10 mm. D) Entire colony counts. Samples were collected on Days 1 (blue), 2 (red) and 3 (green). Note: standard deviation was used to measure variability.</p

mRFP1 can be expressed broadly in Lactobacillus.

<p>The pLEM415-ldhL-mRFP1 vector was transformed into <i>L. casei</i> (B) and <i>L. delbrueckii</i> (D). mRFP1 was detected in both strains. Wild type strains were used as control (A,C). mRFP1 expression (red) is shown in the left panels and DIC images (purple) in the middle. Merged views are shown in the right panels. Scale bars, 20 µm.</p

Different expression levels of Lactobacillus-based expression vectors.

<p>A) Different levels of mRFP1 expression in <i>Lactobacillus casei</i> were detected by Western blot. A total of 0.9 µg of the whole lysate was loaded into each lane. Lane 1, pLEM415-ldhL-mRFP1; lane 2, pLEM415-emr-mRFP1; lane 3, pLEM415-P59-mRFP1; lane 4, pUCYIT-ldhL-mRFP1; lane 5, pUCYIT-emr-mRFP1; lane 6, pUCYIT-P59-mRFP1. B) Quantification of band intensities from Western blot in Panel A. The expression level of pLEM415-ldhL-mRFP1 was set to 100%. Sample numbers correspond to lanes shown in Panel A. C) Wild type <i>Lactobacillus casei</i> colonies under visible light. D) Colonies of <i>Lactobacillus casei</i> transformed with pLEM415-ldhL-mRFP1 appeared pink under visible light. Scale bars, 100 µm.</p