Plateforme Neuro-VIH du CHUV: Intérêts d'une approche multidisciplinaire face aux complications cognitives, neurologiques et psychiatriques du VIH

Le VIH, de par son neurotropisme, peut mener à des complications neurocognitives groupées sous le nom de « HIV-associated neurocognitive disorders » (HAND), qui comprennent, par ordre de sévérité croissante, l'« asymptomatic neurocognitive impairment » (ANI), le « mild neurocognitive disorder » (MND) et la « HIV associated dementia » (HAD). Bien que l'introduction des trithérapies a permis de diminuer l'incidence de la démence liée au VIH, la prévalence des troubes cognitifs mineurs liés au VIH semble augmenter. Ces déficits cognitifs, composés au premier plan de troubles mnésiques, d'un ralentissement psychomoteur et de troubles exécutifs, sont particulièrement handicapants. En outre, les possibilités de dépistage et de traitement pour ces patients s'avèrent très limitées. C'est pourquoi la plateforme Neuro-VIH a pris naissance au CHUV en mars 2011, offrant une aide au diagnostic et à la prise en charge des complications neurocognitives, neurologiques et psychiatriques des patients infectés par le VIH. Les patients séropositifs qui présentent des déficits neurologiques ou neurocognitifs peuvent ainsi être admis à cette plateforme, qui se déroule sur une journée et au cours de laquelle le patient est vu par divers consultants ; un infectiologue, un neurologue, une neuropsychologue et un psychiatre, et divers examens sont effectués (examens sanguins, ponction lombaire et IRM cérébrale). A la fin de cette journée, les divers intervenants de la plateforme se réunissent afin de discuter de chaque cas vu au cours de la journée et émettent un rapport multidisciplinaire comprenant des propositions diagnostiques et de modification de la prise en charge. Le rapport est finalement délivré au médecin traitant du patient. Le but de ce travail est de déterminer quels sont les intérêts d'une telle plateforme dans le cadre de la prise en charge des patients infectés par le VIH et présentant des comorbidités neurologiques, cognitive et/ou psychiatriques, et de comprendre quelles sont les attentes exactes des patients et des médecins envoyeurs. Pour ce, nous avons interviewé par téléphone 72 des 104 patients ayant été vus à la plateforme au moment de notre étude et 39 médecins traitants au travers de deux questionnaires. 54% des patients inteviewés étaient des hommes, 30% étaient âgés de plus de 50 ans, et 80% souffraient de déficits cognitifs. Nous avons ensuite exposé les résultats de ces questionnaires au travers d'un travail d'analyse statistique descriptive. Finalement, nous nous sommes intéressés aux similitudes et divergences existant entre les réponses des patients et leurs propres médecins, et avons tenté de saisir les différences de représentations existant entre les patients les médecins concernant la maladie et sa prise en charge

Mechanical design of NASA Ames Research Center vertical motion simulator

NASA has designed and is constructing a new flight simulator with large vertical travel. Several aspects of the mechanical design of this Vertical Motion Simulator (VMS) are discussed, including the multiple rack and pinion vertical drive, a pneumatic equilibration system, and the friction-damped rigid link catenaries used as cable supports

Predictive value of midsagittal tissue bridges on functional recovery after spinal cord injury

Background: The majority of patients with spinal cord injury (SCI) have anatomically incomplete lesions and present with preserved tissue bridges, yet their outcomes vary. Objective: To assess the predictive value of the anatomical location (ventral/dorsal) and width of preserved midsagittal tissue bridges for American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade conversion and SCI patient stratification into recovery-specific subgroups. Methods: This retrospective longitudinal study includes 70 patients (56 men, age: 52.36 ± 18.58 years) with subacute (ie, 1 month) SCI (45 tetraplegics, 25 paraplegics), 1-month neuroimaging data, and 1-month and 12-month clinical data. One-month midsagittal T2-weighted scans were used to determine the location and width of tissue bridges. Their associations with functional outcomes were assessed using partial correlation and unbiased recursive partitioning conditional inference tree (URP-CTREE). Results: Fifty-seven (81.4%) of 70 patients had tissue bridges (2.53 ± 2.04 mm) at 1-month post-SCI. Larger ventral (P = .001, r = 0.511) and dorsal (P < .001, r = 0.546) tissue bridges were associated with higher AIS conversion rates 12 months post-SCI (n = 39). URP-CTREE analysis identified 1-month ventral tissue bridges as predictors of 12-month total motor scores (0.4 mm cutoff, P = .008), recovery of upper extremity motor scores at 12 months (1.82 mm cutoff, P = .002), 12-month pin-prick scores (1.4 mm cutoff, P = .018), and dorsal tissue bridges at 1 month as predictors of 12-month Spinal Cord Independence Measure scores (0.5 mm cutoff, P = .003). Conclusions: Midsagittal tissue bridges add predictive value to baseline clinical measures for post-SCI recovery. Based on tissue bridges' width, patients can be classified into subgroups of clinical recovery profiles. Midsagittal tissue bridges provide means to optimize patient stratification in clinical trials

Tissue bridges predict neuropathic pain emergence after spinal cord injury

Objective To assess associations between preserved spinal cord tissue quantified by the width of ventral and dorsal tissue bridges and neuropathic pain development after spinal cord injury. Methods This retrospective longitudinal study includes 44 patients (35 men; mean (SD) age, 50.05 (18.88) years) with subacute (ie, 1 month) spinal cord injury (25 patients with neuropathic pain, 19 pain-free patients) and neuroimaging data who had a follow-up clinical assessment at 12 months. Widths of tissue bridges were calculated from midsagittal T2-weighted images and compared across groups. Regression analyses were used to identify relationships between these neuroimaging measures and previously assessed pain intensity and pin-prick score. Results Pin-prick score of the 25 patients with neuropathic pain increased from 1 to 12 months (Δmean=10.08, 95% CI 2.66 to 17.50, p=0.010), while it stayed similar in pain-free patients (Δmean=2.74, 95% CI −7.36 to 12.84, p=0.576). They also had larger ventral tissue bridges (Δmedian=0.80, 95% CI 0.20 to 1.71, p=0.008) at 1 month when compared with pain-free patients. Conditional inference tree analysis revealed that ventral tissue bridges’ width (≤2.1 or >2.1 mm) at 1 month is the strongest predictor for 12 months neuropathic pain intensity (1.90±2.26 and 3.83±1.19, p=0.042) and 12 months pin-prick score (63.84±28.26 and 92.67±19.43, p=0.025). Interpretation Larger width of ventral tissue bridges—a proxy for spinothalamic tract function—at 1 month post-spinal cord injury is associated with the emergence and maintenance of neuropathic pain and increased pin-prick sensation. Spared ventral tissue bridges could serve as neuroimaging biomarkers of neuropathic pain and might be used for prediction and monitoring of pain outcomes and stratification of patients in interventional trials

Longitudinal changes of spinal cord grey and white matter following spinal cord injury

Objectives: Traumatic and non-traumatic spinal cord injury produce neurodegeneration across the entire neuraxis. However, the spatiotemporal dynamics of spinal cord grey and white matter neurodegeneration above and below the injury is understudied. // Methods: We acquired longitudinal data from 13 traumatic and 3 non-traumatic spinal cord injury patients (8–8 cervical and thoracic cord injuries) within 1.5 years after injury and 10 healthy controls over the same period. The protocol encompassed structural and diffusion-weighted MRI rostral (C2/C3) and caudal (lumbar enlargement) to the injury level to track tissue-specific neurodegeneration. Regression models assessed group differences in the temporal evolution of tissue-specific changes and associations with clinical outcomes. // Results: At 2 months post-injury, white matter area was decreased by 8.5% and grey matter by 15.9% in the lumbar enlargement, while at C2/C3 only white matter was decreased (−9.7%). Patients had decreased cervical fractional anisotropy (FA: −11.3%) and increased radial diffusivity (+20.5%) in the dorsal column, while FA was lower in the lateral (−10.3%) and ventral columns (−9.7%) of the lumbar enlargement. White matter decreased by 0.34% and 0.35% per month at C2/C3 and lumbar enlargement, respectively, and grey matter decreased at C2/C3 by 0.70% per month. // Conclusions: This study describes the spatiotemporal dynamics of tissue-specific spinal cord neurodegeneration above and below a spinal cord injury. While above the injury, grey matter atrophy lagged initially behind white matter neurodegeneration, in the lumbar enlargement these processes progressed in parallel. Tracking trajectories of tissue-specific neurodegeneration provides valuable assessment tools for monitoring recovery and treatment effects

Longitudinal changes of spinal cord grey and white matter following spinal cord injury

Objectives: Traumatic and non-traumatic spinal cord injury produce neurodegeneration across the entire neuraxis. However, the spatiotemporal dynamics of spinal cord grey and white matter neurodegeneration above and below the injury is understudied. Methods: We acquired longitudinal data from 13 traumatic and 3 non-traumatic spinal cord injury patients (8-8 cervical and thoracic cord injuries) within 1.5 years after injury and 10 healthy controls over the same period. The protocol encompassed structural and diffusion-weighted MRI rostral (C2/C3) and caudal (lumbar enlargement) to the injury level to track tissue-specific neurodegeneration. Regression models assessed group differences in the temporal evolution of tissue-specific changes and associations with clinical outcomes. Results: At 2 months post-injury, white matter area was decreased by 8.5% and grey matter by 15.9% in the lumbar enlargement, while at C2/C3 only white matter was decreased (-9.7%). Patients had decreased cervical fractional anisotropy (FA: -11.3%) and increased radial diffusivity (+20.5%) in the dorsal column, while FA was lower in the lateral (-10.3%) and ventral columns (-9.7%) of the lumbar enlargement. White matter decreased by 0.34% and 0.35% per month at C2/C3 and lumbar enlargement, respectively, and grey matter decreased at C2/C3 by 0.70% per month. Conclusions: This study describes the spatiotemporal dynamics of tissue-specific spinal cord neurodegeneration above and below a spinal cord injury. While above the injury, grey matter atrophy lagged initially behind white matter neurodegeneration, in the lumbar enlargement these processes progressed in parallel. Tracking trajectories of tissue-specific neurodegeneration provides valuable assessment tools for monitoring recovery and treatment effects

Safety of human immunisation with a live-attenuated Mycobacterium tuberculosis vaccine: a randomised, double-blind, controlled phase I trial.

BACKGROUND: Tuberculosis remains one of the world's deadliest transmissible diseases despite widespread use of the BCG vaccine. MTBVAC is a new live tuberculosis vaccine based on genetically attenuated Mycobacterium tuberculosis that expresses most antigens present in human isolates of M tuberculosis. We aimed to compare the safety of MTBVAC with BCG in healthy adult volunteers. METHODS: We did this single-centre, randomised, double-blind, controlled phase 1 study at the Centre Hospitalier Universitaire Vaudois (CHUV; Lausanne, Switzerland). Volunteers were eligible for inclusion if they were aged 18-45 years, clinically healthy, HIV-negative and tuberculosis-negative, and had no history of active tuberculosis, chemoprophylaxis for tuberculosis, or BCG vaccination. Volunteers fulfilling the inclusion criteria were randomly assigned to three cohorts in a dose-escalation manner. Randomisation was done centrally by the CHUV Pharmacy and treatments were masked from the study team and volunteers. As participants were recruited within each cohort, they were randomly assigned 3:1 to receive MTBVAC or BCG. Of the participants allocated MTBVAC, those in the first cohort received 5 × 10(3) colony forming units (CFU) MTBVAC, those in the second cohort received 5 × 10(4) CFU MTBVAC, and those in the third cohort received 5 × 10(5) CFU MTBVAC. In all cohorts, participants assigned to receive BCG were given 5 × 10(5) CFU BCG. Each participant received a single intradermal injection of their assigned vaccine in 0·1 mL sterile water in their non-dominant arm. The primary outcome was safety in all vaccinated participants. Secondary outcomes included whole blood cell-mediated immune response to live MTBVAC and BCG, and interferon γ release assays (IGRA) of peripheral blood mononuclear cells. This trial is registered with ClinicalTrials.gov, number NCT02013245. FINDINGS: Between Jan 23, 2013, and Nov 6, 2013, we enrolled 36 volunteers into three cohorts, each of which consisted of nine participants who received MTBVAC and three who received BCG. 34 volunteers completed the trial. The safety of vaccination with MTBVAC at all doses was similar to that of BCG, and vaccination did not induce any serious adverse events. All individuals were IGRA negative at the end of follow-up (day 210). After whole blood stimulation with live MTBVAC or BCG, MTBVAC was at least as immunogenic as BCG. At the same dose as BCG (5×10(5) CFU), although no statistical significance could be achieved, there were more responders in the MTBVAC group than in the BCG group, with a greater frequency of polyfunctional CD4+ central memory T cells. INTERPRETATION: To our knowledge, MTBVAC is the first live-attenuated M tuberculosis vaccine to reach clinical assessment, showing similar safety to BCG. MTBVAC seemed to be at least as immunogenic as BCG, but the study was not powered to investigate this outcome. Further plans to use more immunogenicity endpoints in a larger number of volunteers (adults and adolescents) are underway, with the aim to thoroughly characterise and potentially distinguish immunogenicity between MTBVAC and BCG in tuberculosis-endemic countries. Combined with an excellent safety profile, these data support advanced clinical development in high-burden tuberculosis endemic countries. FUNDING: Biofabri and Bill &amp; Melinda Gates Foundation through the TuBerculosis Vaccine Initiative (TBVI)

Tracking cells in Life Cell Imaging videos using topological alignments

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Expansion of Agriculture in Northern Cold-Climate Regions: A Cross-Sectoral Perspective on Opportunities and Challenges

Agriculture in the boreal and Arctic regions is perceived as marginal, low intensity and inadequate to satisfy the needs of local communities, but another perspective is that northern agriculture has untapped potential to increase the local supply of food and even contribute to the global food system. Policies across northern jurisdictions target the expansion and intensification of agriculture, contextualized for the diverse social settings and market foci in the north. However, the rapid pace of climate change means that traditional methods of adapting cropping systems and developing infrastructure and regulations for this region cannot keep up with climate change impacts. Moreover, the anticipated conversion of northern cold-climate natural lands to agriculture risks a loss of up to 76% of the carbon stored in vegetation and soils, leading to further environmental impacts. The sustainable development of northern agriculture requires local solutions supported by locally relevant policies. There is an obvious need for the rapid development of a transdisciplinary, cross-jurisdictional, long-term knowledge development, and dissemination program to best serve food needs and an agricultural economy in the boreal and Arctic regions while minimizing the risks to global climate, northern ecosystems and communities

High-Resolution Quantification of Focal Adhesion Spatiotemporal Dynamics in Living Cells

Focal adhesions (FAs) are macromolecular complexes that provide a linkage between the cell and its external environment. In a motile cell, focal adhesions change size and position to govern cell migration, through the dynamic processes of assembly and disassembly. To better understand the dynamic regulation of focal adhesions, we have developed an analysis system for the automated detection, tracking, and data extraction of these structures in living cells. This analysis system was used to quantify the dynamics of fluorescently tagged Paxillin and FAK in NIH 3T3 fibroblasts followed via Total Internal Reflection Fluorescence Microscopy (TIRF). High content time series included the size, shape, intensity, and position of every adhesion present in a living cell. These properties were followed over time, revealing adhesion lifetime and turnover rates, and segregation of properties into distinct zones. As a proof-of-concept, we show how a single point mutation in Paxillin at the Jun-kinase phosphorylation site Serine 178 changes FA size, distribution, and rate of assembly. This study provides a detailed, quantitative picture of FA spatiotemporal dynamics as well as a set of tools and methodologies for advancing our understanding of how focal adhesions are dynamically regulated in living cells. A full, open-source software implementation of this pipeline is provided at http://gomezlab.bme.unc.edu/tools