Bio-ORACLE: a global environmental dataset for marine species distribution modeling

The oceans harbor a great diversity of organisms whose distribution and ecological preferences are often poorly understood. Species distribution modeling (SDM) could improve our knowledge and inform marine ecosystem management and conservation. Although marine environmental data are available from various sources, there are currently no user-friendly, high-resolution global datasets designed for SDM applications. This study aims to ?ll this gap by assembling a comprehensive, uniform, high-resolution and readily usable package of global environmental rasters. We compiled global coverage data, e.g. satellite-based and in situ measured data, representing various aspects of the marine environment relevant for species distributions. Rasters were assembled at a resolution of 5 arcmin (c. 9.2 km) and a uniform landmask was applied. The utility of the dataset was evaluated by maximum entropy SDM of the invasive seaweed Codium fragile ssp. fragile. We present Bio-ORACLE (ocean rasters for analysis of climate and environment), a global dataset consisting of 23 geophysical, biotic and climate rasters. This user-friendly data package for marine species distribution modeling is available for download at http://www.bio-oracle.ugent.be. The high predictive power of the distribution model of C. fragile ssp. fragile clearly illustrates the potential of the data package for SDM of shallow-water marine organisms. The availability of this global environmental data package has the potential to stimulate marine SDM. The high predictive success of the presence-only model of a notorious invasive seaweed shows that the information contained in Bio-ORACLE can be informative about marine distributions and permits building highly accurate species distribution models

The effect of two different Individually Ventilated Cage systems on anxiety-related behaviour and welfare in two strains of laboratory mouse

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Weak Liouville-Arnold Theorems & Their Implications

This paper studies the existence of invariant smooth Lagrangian graphs for Tonelli Hamiltonian systems with symmetries. In particular, we consider Tonelli Hamiltonians with n independent but not necessarily involutive constants of motion and obtain two theorems reminiscent of the Liouville-Arnold theorem. Moreover, we also obtain results on the structure of the configuration spaces of such systems that are reminiscent of results on the configuration space of completely integrable Tonelli Hamiltonians.Comment: 24 pages, 1 figure; v2 corrects typo in online abstract; v3 includes new title (was: A Weak Liouville-Arnold Theorem), re-arrangement of introduction, re-numbering of main theorems; v4 updates the authors' email and physical addresses, clarifies notation in section 4. Final versio

Pervasive and opposing effects of Unpredictable Chronic Mild Stress (UCMS) on hippocampal gene expression in BALB/cJ and C57BL/6J mouse strains

Background: BALB/cJ is a strain susceptible to stress and extremely susceptible to a defective hedonic impact in response to chronic stressors. The strain offers much promise as an animal model for the study of stress related disorders. We present a comparative hippocampal gene expression study on the effects of unpredictable chronic mild stress on BALB/cJ and C57BL/6J mice. Affymetrix MOE 430 was used to measure hippocampal gene expression from 16 animals of two different strains (BALB/cJ and C57BL/6J) of both sexes and subjected to either unpredictable chronic mild stress (UCMS) or no stress. Differences were statistically evaluated through supervised and unsupervised linear modelling and using Weighted Gene Coexpression Network Analysis (WGCNA). In order to gain further understanding into mechanisms related to stress response, we cross-validated our results with a parallel study from the GENDEP project using WGCNA in a meta-analysis design. Results: The effects of UCMS are visible through Principal Component Analysis which highlights the stress sensitivity of the BALB/cJ strain. A number of genes and gene networks related to stress response were uncovered including the Creb1 gene. WGCNA and pathway analysis revealed a gene network centered on Nfkb1. Results from the meta-analysis revealed a highly significant gene pathway centred on the Ubiquitin C (Ubc) gene. All pathways uncovered are associated with inflammation and immune response. Conclusions: The study investigated the molecular mechanisms underlying the response to adverse environment in an animal model using a GxE design. Stress-related differences were visible at the genomic level through PCA analysis highlighting the high sensitivity of BALB/cJ animals to environmental stressors. Several candidate genes and gene networks reported are associated with inflammation and neurogenesis and could serve to inform candidate gene selection in human studies and provide additional insight into the pathology of Major Depressive Disorder

Rituximab in early systemic sclerosis

Objectives (1) Hypothesis testing of the potency of rituximab (RTX) in preventing fibrotic complications and (2) assessing acceptability and feasibility of RTX in early systemic sclerosis (SSc). Methods A small, 24-month, randomised, double-blind, placebo-controlled, single-centre trial in patients with SSc diagnosed <2 years was conducted. Patients received RTX or placebo infusions at t=0, t=15 days and t=6 months. Patients were clinically evaluated every 3 months, with lung function tests and high-resolution CT every other visit. Skin biopsies were taken at baseline and month 3. Immunophenotyping of peripheral blood mononuclear cells was performed at every visit, except at months 9 and 18. Adverse events, course of skin and pulmonary involvement and B cell populations in skin and peripheral blood were evaluated. Results In total 16, patients (rituximab n=8, placebo n=8) were included. Twelve patients had diffuse cutaneous SS

regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomized, placebo-controlled, phase 3 trial.

Summary Background No treatment options are available for patients with metastatic colorectal cancer that progresses after all approved standard therapies, but many patients maintain a good performance status and could be candidates for further therapy. An international phase 3 trial was done to assess the multikinase inhibitor regorafenib in these patients. Methods We did this trial at 114 centres in 16 countries. Patients with documented metastatic colorectal cancer and progression during or within 3 months after the last standard therapy were randomised (in a 2:1 ratio; by computer-generated randomisation list and interactive voice response system; preallocated block design (block size six); stratified by previous treatment with VEGF-targeting drugs, time from diagnosis of metastatic disease, and geographical region) to receive best supportive care plus oral regorafenib 160 mg or placebo once daily, for the first 3 weeks of each 4 week cycle. The primary endpoint was overall survival. The study sponsor, participants, and investigators were masked to treatment assignment. Efficacy analyses were by intention to treat. This trial is registered at ClinicalTrials.gov, number NCT01103323. Findings Between April 30, 2010, and March 22, 2011, 1052 patients were screened, 760 patients were randomised to receive regorafenib (n=505) or placebo (n=255), and 753 patients initiated treatment (regorafenib n=500; placebo n=253; population for safety analyses). The primary endpoint of overall survival was met at a preplanned interim analysis; data cutoff was on July 21, 2011. Median overall survival was 6·4 months in the regorafenib group versus 5·0 months in the placebo group (hazard ratio 0·77; 95% CI 0·64–0·94; one-sided p=0·0052). Treatment-related adverse events occurred in 465 (93%) patients assigned regorafenib and in 154 (61%) of those assigned placebo. The most common adverse events of grade three or higher related to regorafenib were hand-foot skin reaction (83 patients, 17%), fatigue (48, 10%), diarrhoea (36, 7%), hypertension (36, 7%), and rash or desquamation (29, 6%). Interpretation Regorafenib is the first small-molecule multikinase inhibitor with survival benefits in metastatic colorectal cancer which has progressed after all standard therapies. The present study provides evidence for a continuing role of targeted treatment after disease progression, with regorafenib offering a potential new line of therapy in this treatment-refractory population