ATHLETIQUE: interest of an adapted physical activity program in patients with juvenile idiopathic arthritis: a feasibility and preliminary effectiveness study

BackgroundJuvenile Idiopathic Arthritis (JIA) is associated with joint inflammation, pain and limited joint mobility, impacting the practice of physical activities. Adapted Physical Activities (APA) are an increasingly used method of rehabilitation, but additional studies are needed to define the nature of the most appropriate physical activity for patients with JIA. The “ATHLETIQUE” project aims to evaluate the impact of a program integrating APA sessions with use of a pedometer watch, on disease activity in patients with JIA.MethodsThis study will be a randomized, multicenter, open-label, controlled clinical trial with 2 parallel arms. The patients included in this study will be children and adolescents with JIA, aged 6 to 17 years. The experimental group (30 patients) will participate in an APA program for 3 months and will use a pedometer watch for one year. We will evaluate and compare the change in disease activity measurements (primary objective), fatigue, pain, quality of life, level of physical activity, functional capacities, and muscle strength (secondary objectives) after 14, 26 and 50 weeks. The control group (10 patients) will undergo the same evaluations as the experimental group but will not participate in the APA program and will not wear the pedometer watch.Expected resultsThe APA program may help to promote an active lifestyle with regular physical activity, preventing comorbidities and motor disability. Promising results on disease activity, functional capacities and quality of life would enable us to envisage a larger research program with a view to optimizing and assessing APA for children with JIA.DiscussionThis study will be conducted in the short and medium-term, with one-year follow-up, including 3 months of APA sessions for the experimental group. The sessions proposed during the APA program will mainly be aerobic and bodyweight exercises. Furthermore, in contrast to previous studies on this topic, our study will integrate a novel element, namely the use of a pedometer watch. This watch will help to implement strategies to address motivation. This study aims to improve physical and mental well-being, provide a basis for the design of a larger study, and propose recommendations adapted to children with JIA.Trial registrationRegistered with ClinicalTrials.gov under the number NCT0557242

Long-Term Mortality in Patients with Tuberculous Meningitis: A Danish Nationwide Cohort Study

Background: With high short-term mortality and substantial excess morbidity among survivors, tuberculous meningitis (TBM) is the most severe manifestation of extra-pulmonary tuberculosis (TB). The objective of this study was to assess the long-term mortality and causes of death in a TBM patient population compared to the background population. Methods: A nationwide cohort study was conducted enrolling patients notified with TBM in Denmark from 1972–2008 and alive one year after TBM diagnosis. Data was extracted from national registries. From the background population we identified a control cohort of individuals matched on gender and date of birth. Kaplan-Meier survival curves and Cox regression analysis were used to estimate mortality rate ratios (MRR) and analyse causes of death. Findings: A total of 55 TBM patients and 550 individuals from the background population were included in the study. Eighteen patients (32.7%) and 107 population controls (19.5%) died during the observation period. The overall MRR was 1.79 (95%CI: 1.09–2.95) for TBM patients compared to the population control cohort. TBM patients in the age group 31–60 years at time of diagnosis had the highest relative risk of death (MRR 2.68; 95%CI 1.34–5.34). The TBM patients had a higher risk of death due to infectious disease, but not from other causes of death. Conclusion: Adult TBM patients have an almost two-fold increased long-term mortality and the excess mortality stems fro

Ideas and perspectives: strengthening the biogeosciences in environmental research networks

Many scientific approaches are improving our understanding and management of the rapidly changing environment. Long-term environmental research networks are one approach to advancing local, regional, and global environmental science and education. A remarkable number and wide variety of environmental research networks operate around the world today. These are diverse in funding, infrastructure, motivating questions, scientific strengths, and the sciences that birthed and maintained the networks. Some networks have individual sites that were selected because they had produced invaluable long-term data, while other networks have new sites selected to span ecological gradients. However, all long-term environmental networks share two challenges. Networks must keep pace with scientific advances and interact with both the scientific community and society at large. If networks fall short of successfully addressing these challenges, they risk becoming irrelevant. The objective of this paper is to assert that the biogeosciences offer environmental research networks a number of opportunities to expand scientific impact and public engagement. We explore some of these opportunities with four networks: the International Long Term Ecological Research programs (ILTERs), the Critical Zone Observatories (CZOs), the Earth and Ecological Observatory networks (EONs), and the FLUXNET program of eddy flux sites. While these networks were founded and grown by interdisciplinary scientists, the preponderance of expertise and funding have gravitated activities of ILTERs and EONs toward ecology and biology, CZOs toward the Earth sciences and geology, and FLUXNET toward ecophysiology and micrometeorology. Our point is not to homogenize networks, nor to diminish disciplinary science. Rather, we argue that by more fully incorporating the integration of biology and geology in long-term environmental research networks, scientists can better leverage network assets, keep pace with the ever-changing science of the environment, and engage with larger scientific and public audiences

Optimizing process-based models to predict current and future soil organic carbon stocks at high-resolution

From hillslope to small catchment scales (&lt;&thinsp;50 km2), soil carbon management and mitigation policies rely on estimates and projections of soil organic carbon (SOC) stocks. Here we apply a process-based modeling approach that parameterizes the MIcrobial-MIneral Carbon Stabilization (MIMICS) model with SOC measurements and remotely sensed environmental data from the Reynolds Creek Experimental Watershed in SW Idaho, USA. Calibrating model parameters reduced error between simulated and observed SOC stocks by 25%, relative to the initial parameter estimates and better captured local gradients in climate and productivity. The calibrated parameter ensemble was used to produce spatially continuous, high-resolution (10&nbsp;m2) estimates of stocks and associated uncertainties of litter, microbial biomass, particulate, and protected SOC pools across the complex landscape. Subsequent projections of SOC response to idealized environmental disturbances illustrate the spatial complexity of potential SOC vulnerabilities across the watershed. Parametric uncertainty generated physicochemically protected soil C stocks that varied by a mean factor of 4.4&thinsp;&times;&thinsp;across individual locations in the watershed and a &minus;&thinsp;14.9 to +&thinsp;20.4% range in potential SOC stock response to idealized disturbances, illustrating the need for additional measurements of soil carbon fractions and their turnover time to improve confidence in the MIMICS simulations of SOC dynamics. </div

Phase 1 Trials of rVSV Ebola Vaccine in Africa and Europe.

BACKGROUND: The replication-competent recombinant vesicular stomatitis virus (rVSV)-based vaccine expressing a Zaire ebolavirus (ZEBOV) glycoprotein was selected for rapid safety and immunogenicity testing before its use in West Africa. METHODS: We performed three open-label, dose-escalation phase 1 trials and one randomized, double-blind, controlled phase 1 trial to assess the safety, side-effect profile, and immunogenicity of rVSV-ZEBOV at various doses in 158 healthy adults in Europe and Africa. All participants were injected with doses of vaccine ranging from 300,000 to 50 million plaque-forming units (PFU) or placebo. RESULTS: No serious vaccine-related adverse events were reported. Mild-to-moderate early-onset reactogenicity was frequent but transient (median, 1 day). Fever was observed in up to 30% of vaccinees. Vaccine viremia was detected within 3 days in 123 of the 130 participants (95%) receiving 3 million PFU or more; rVSV was not detected in saliva or urine. In the second week after injection, arthritis affecting one to four joints developed in 11 of 51 participants (22%) in Geneva, with pain lasting a median of 8 days (interquartile range, 4 to 87); 2 self-limited cases occurred in 60 participants (3%) in Hamburg, Germany, and Kilifi, Kenya. The virus was identified in one synovial-fluid aspirate and in skin vesicles of 2 other vaccinees, showing peripheral viral replication in the second week after immunization. ZEBOV-glycoprotein-specific antibody responses were detected in all the participants, with similar glycoprotein-binding antibody titers but significantly higher neutralizing antibody titers at higher doses. Glycoprotein-binding antibody titers were sustained through 180 days in all participants. CONCLUSIONS: In these studies, rVSV-ZEBOV was reactogenic but immunogenic after a single dose and warrants further evaluation for safety and efficacy. (Funded by the Wellcome Trust and others; ClinicalTrials.gov numbers, NCT02283099, NCT02287480, and NCT02296983; Pan African Clinical Trials Registry number, PACTR201411000919191.)

Novelty-Related fMRI Responses of Precuneus and Medial Temporal Regions in Individuals at Risk for Alzheimer Disease

BACKGROUND AND OBJECTIVES: We assessed whether novelty-related fMRI activity in medial temporal lobe regions and the precuneus follows an inverted U-shaped pattern across the clinical spectrum of increased Alzheimer disease (AD) risk as previously suggested. Specifically, we tested for potentially increased activity in individuals with a higher AD risk due to subjective cognitive decline (SCD) or mild cognitive impairment (MCI). We further tested whether activity differences related to diagnostic groups were accounted for by CSF markers of AD or brain atrophy. METHODS: We studied 499 participants aged 60-88 years from the German Center for Neurodegenerative Diseases Longitudinal Cognitive Impairment and Dementia Study (DELCODE) who underwent task-fMRI. Participants included 163 cognitively normal (healthy control, HC) individuals, 222 SCD, 82 MCI, and 32 patients with clinical diagnosis of mild AD. CSF levels of β-amyloid 42/40 ratio and phosphorylated-tau181 were available from 232 participants. We used region-based analyses to assess novelty-related activity (novel > highly familiar scenes) in entorhinal cortex, hippocampus, and precuneus as well as whole-brain voxel-wise analyses. First, general linear models tested differences in fMRI activity between participant groups. Complementary regression models tested quadratic relationships between memory impairment and activity. Second, relationships of activity with AD CSF biomarkers and brain volume were analyzed. Analyses were controlled for age, sex, study site, and education. RESULTS: In the precuneus, we observed an inverted U-shaped pattern of novelty-related activity across groups, with higher activity in SCD and MCI compared with HC, but not in patients with AD who showed relatively lower activity than MCI. This nonlinear pattern was confirmed by a quadratic relationship between memory impairment and precuneus activity. Precuneus activity was not related to AD biomarkers or brain volume. In contrast to the precuneus, hippocampal activity was reduced in AD dementia compared with all other groups and related to AD biomarkers. DISCUSSION: Novelty-related activity in the precuneus follows a nonlinear pattern across the clinical spectrum of increased AD risk. Although the underlying mechanism remains unclear, increased precuneus activity might represent an early signature of memory impairment. Our results highlight the nonlinearity of activity alterations that should be considered in clinical trials using functional outcome measures or targeting hyperactivity

Divergent evolution in the genomes of closely related lacertids, <i>Lacerta viridis</i> and <i>L. bilineata</i>, and implications for speciation

Lacerta viridis and Lacerta bilineata are sister species of European green lizards (eastern and western clades, respectively) that, until recently, were grouped together as the L. viridis complex. Genetic incompatibilities were observed between lacertid populations through crossing experiments, which led to the delineation of two separate species within the L. viridis complex. The population history of these sister species and processes driving divergence are unknown. We constructed the first high-quality de novo genome assemblies for both L. viridis and L. bilineata through Illumina and PacBio sequencing, with annotation support provided from transcriptome sequencing of several tissues. To estimate gene flow between the two species and identify factors involved in reproductive isolation, we studied their evolutionary history, identified genomic rearrangements, detected signatures of selection on non-coding RNA, and on protein-coding genes.Here we show that gene flow was primarily unidirectional from L. bilineata to L. viridis after their split at least 1.15 million years ago. We detected positive selection of the non-coding repertoire; mutations in transcription factors; accumulation of divergence through inversions; selection on genes involved in neural development, reproduction, and behavior, as well as in ultraviolet-response, possibly driven by sexual selection, whose contribution to reproductive isolation between these lacertid species needs to be further evaluated.The combination of short and long sequence reads resulted in one of the most complete lizard genome assemblies. The characterization of a diverse array of genomic features provided valuable insights into the demographic history of divergence among European green lizards, as well as key species differences, some of which are candidates that could have played a role in speciation. In addition, our study generated valuable genomic resources that can be used to address conservation-related issues in lacertids