Strong Convergence towards homogeneous cooling states for dissipative Maxwell models

We show the propagation of regularity, uniformly in time, for the scaled solutions of the inelastic Maxwell model for small inelasticity. This result together with the weak convergence towards the homogenous cooling state present in the literature implies the strong convergence in Sobolev norms and in the $L^1$ norm towards it depending on the regularity of the initial data. The strategy of the proof is based on a precise control of the growth of the Fisher information for the inelastic Boltzmann equation. Moreover, as an application we obtain a bound in the $L^1$ distance between the homogeneous cooling state and the corresponding Maxwellian distribution vanishing as the inelasticity goes to zero.Comment: 2 figure

The infectious synapse formed between mature dendritic cells and CD4 + T cells is independent of the presence of the HIV-1 envelope glycoprotein

Altres ajuts:This work was supported the Spanish AIDS Network (RD06/0006), the Catalan HIV Vaccine Development Program (HIVACAT), and the Spanish Foundation for AIDS Research and Prevention (FIPSE) project 36750/08.Since cell-mediated infection of human immunodeficiency virus type 1 (HIV-1) is more efficient than cell-free infection, cell-to-cell propagation plays a crucial role in the pathogenesis of HIV-1 infection. Transmission of HIV-1 is enabled by two types of cellular contacts, namely, virological synapses between productively infected cells and uninfected target cells and infectious synapses between uninfected dendritic cells (DC) harboring HIV-1 and uninfected target cells. While virological synapses are driven by expression of the viral envelope glycoprotein on the cell surface, little is known about the role of envelope glycoprotein during contact between DC and T cells. We explored the contribution of HIV-1 envelope glycoprotein, adhesion molecules, and antigen recognition in the formation of conjugates comprising mature DC (mDC) and CD4 + T cells in order to further evaluate their role in mDC-mediated HIV-1 transmission at the immunological synapse. Unlike virological synapse, HIV-1 did not modulate the formation of cell conjugates comprising mDC harboring HIV-1 and non-activated primary CD4 + T cells. Disruption of interactions between ICAM-1 and LFA-1, however, resulted in a 60% decrease in mDC-CD4 + T-cell conjugate formation and, consequently, in a significant reduction of mDC-mediated HIV-1 transmission to non-activated primary CD4 + T cells (p < 0.05). Antigen recognition or sustained MHC-TcR interaction did not enhance conjugate formation, but significantly boosted productive mDC-mediated transmission of HIV-1 (p < 0.05) by increasing T-cell activation and proliferation. Formation of the infectious synapse is independent of the presence of the HIV-1 envelope glycoprotein, although it does require an interaction between ICAM-1 and LFA-1. This interaction is the main driving force behind the formation of mDC-CD4 + T-cell conjugates and enables transmission of HIV-1 to CD4 + T cells. Moreover, antigen recognition boosts HIV-1 replication without affecting the frequency of cellular conjugates. Our results suggest a determinant role for immune activation driven by mDC-CD4 + T-cell contacts in viral dissemination and that this activation likely contributes to the pathogenesis of HIV-1 infection

Ethical challenges in preclinical Alzheimer's disease observational studies and trials:Results of the Barcelona summit

AbstractAlzheimer's disease (AD) is among the most significant health care burdens. Disappointing results from clinical trials in late-stage AD persons combined with hopeful results from trials in persons with early-stage suggest that research in the preclinical stage of AD is necessary to define an optimal therapeutic success window. We review the justification for conducting trials in the preclinical stage and highlight novel ethical challenges that arise and are related to determining appropriate risk-benefit ratios and disclosing individuals' biomarker status. We propose that to conduct clinical trials with these participants, we need to improve public understanding of AD using unified vocabulary, resolve the acceptable risk-benefit ratio in asymptomatic participants, and disclose or not biomarker status with attention to study type (observational studies vs clinical trials). Overcoming these challenges will justify clinical trials in preclinical AD at the societal level and aid to the development of societal and legal support for trial participants

Paired spawning with male rotation of meagre Argyrosomus regius using GnRHa injections, as a method for producing multiple families for breeding selection programs

Weekly gonadotropin-releasing hormone agonist (GnRHa) injections were used to induce spawning in paired male and female meagre (Argyrosomus regius) with a weekly rotation of the males, in order to produce a large number of families, as a method to facilitate selective breeding programs. Two different broodstocks were used (HCMR and IRTA), with females of mean weights of 11.7 ± 2.6 kg and 20.0 ± 1.8 kg, and males of 10.2 ± 1.2 kg and 15.1 ± 1.0 kg, respectively. A single GnRHa injection of 15 μg kg−1 was administered to each selected female, and 7.5 or 15 μg kg−1 to each male to induce spawning. In the subsequent weeks, maturity was checked and fish were induced as above, but males (n = 18) were rotated to form a different pair with the selected females (n = 21). Experiments finished when all paired combinations had been completed or a fish lost maturity status and could not be induced further. A total of 56 families were produced with a mean number of eggs from each family of 87,666 ± 11,244 eggs kg−1. There was a decline in the fecundity, number of spawns and percentage of pairs that spawned successfully after consecutive weekly GnRHa injections. Relative fecundity declined significantly from 134,495 ± 25,557 eggs kg−1 female body weight after the first injection, to 44,252 ± 17,638 eggs kg−1 after the fourth injection. However, there were no differences amongst weeks in egg fertilization success, hatching success or larval survival to 5 days post hatch. The decrease in fecundity and spawning success was attributed to a loss of maturity observed in the females, which may be related to differences in mate selection strategies between male and female meagre. The study demonstrated that paired spawning with male rotation was a successful method that can be used for breeding programs to produce a limit of three families per female or as a scaling up step to produce large numbers of offspring from a limited number of selected pairs.info:eu-repo/semantics/acceptedVersio

Veteran teachers' identity: what does the research literature tell us?

This paper provides an overview of research on veteran teachers and teacher identity. It analyses issues at the personal, situated and professional levels that have been shown to impact on veteran teachers' identities. The search included empirical studies published in peer-reviewed journals between 2005 and 2016. In total, 19 papers were analysed. Findings revealed that many studies focused on veteran teachers' resilience. Issues concerning veteran teachers' identities are key to understanding why they remain in the profession and are able to sustain their motivation and commitment over time. Many veteran teachers portrayed in the literature built on their confidence regarding their professional competence and relied on internal and external issues to maintain their motivation and commitment to teaching. The role of emotions in the transformation of veteran teachers' identities and the permeable boundaries of the personal, situated and professional scenarios influencing veteran teachers' identities are highlighted in the paper.Financial Support by CIEC (Research Centre on Child Studies, IE, UMinho; FCT R&D unit 317, Portugal) by the Strategic Project UID/CED/00317/2013, with financial support of National Funds through the FCT (Foundation for Science and Technology) and co-financed by European Regional Development Funds (FEDER) through the COMPETE 2020 - Competitiveness and Internationalization Operational Program (POCI) with the reference POCI-01-0145-FEDER-00756

Patient and caregiver assessment of the benefits from the clinical use of amyloid PET imaging

INTRODUCTION: Few studies to date have explored patient and caregiver views on the clinical use of amyloid positron emission tomography (PET). METHODS: A 7-item questionnaire assessing patient and caregiver views (510 total respondents) toward amyloid PET imaging was advertised broadly through alz.org/trialmatch. RESULTS: We received 510 unique responses from 48 US states, 2 Canadian provinces, the Dominican Republic, and Greece. Both patients and caregivers indicated that they would want to receive amyloid imaging if offered the opportunity. Over 88% of respondents had a positive response (∼10% with neutral and 2% with negative responses) to whether amyloid PET should be offered routinely and be reimbursed. Such information was felt to be useful for long-term legal, financial, and health care planning. Respondents identifying with early age cognitive decline (younger than 65 y) were more likely to explore options for disability insurance (P=0.03). Responders from the Midwest were more likely to utilize information from amyloid imaging for legal planning (P=0.02), disability insurance (P=0.02), and life insurance (P=0.04) than other US regions. DISCUSSION: Patients and caregivers supported the use of amyloid PET imaging in clinical practice and felt that the information would provide significant benefits particularly in terms of future planning

Revolutionizing Alzheimer\u27s disease and clinical trials through biomarkers

AbstractThe Alzheimer's Association's Research Roundtable met in May 2014 to explore recent progress in developing biomarkers to improve understanding of disease pathogenesis and expedite drug development. Although existing biomarkers have proved extremely useful for enrichment of subjects in clinical trials, there is a clear need to develop novel biomarkers that are minimally invasive and that more broadly characterize underlying pathogenic mechanisms, including neurodegeneration, neuroinflammation, and synaptic dysfunction. These may include blood-based assays and new neuropsychological testing protocols, as well as novel ligands for positron emission tomography imaging, and advanced magnetic resonance imaging methodologies. In addition, there is a need for biomarkers that can serve as theragnostic markers of response to treatment. Standardization remains a challenge, although international consortia have made substantial progress in this area and provide lessons for future standardization efforts

rPOP: Robust PET-Only Processing of Community Acquired Heterogeneous Amyloid-PET Data

The reference standard for amyloid-PET quantification requires structural MRI (sMRI) for preprocessing in both multi-site research studies and clinical trials. Here we describe rPOP (robust PET-Only Processing), a MATLAB-based MRI-free pipeline implementing non-linear warping and differential smoothing of amyloid-PET scans performed with any of the FDA-approved radiotracers (18F-florbetapir/FBP, 18F-florbetaben/FBB or 18F-flutemetamol/FLUTE). Each image undergoes spatial normalization based on weighted PET templates and data-driven differential smoothing, then allowing users to perform their quantification of choice. Prior to normalization, users can choose whether to automatically reset the origin of the image to the center of mass or proceed with the pipeline with the image as it is. We validate rPOP with n = 740 (514 FBP, 182 FBB, 44 FLUTE) amyloid-PET scans from the Imaging Dementia—Evidence for Amyloid Scanning – Brain Health Registry sub-study (IDEAS-BHR) and n = 1,518 scans from the Alzheimer\u27s Disease Neuroimaging Initiative (n = 1,249 FBP, n = 269 FBB), including heterogeneous acquisition and reconstruction protocols. After running rPOP, a standard quantification to extract Standardized Uptake Value ratios and the respective Centiloids conversion was performed. rPOP-based amyloid status (using an independent pathology-based threshold of ≥24.4 Centiloid units) was compared with either local visual reads (IDEAS-BHR, n = 663 with complete valid data and reads available) or with amyloid status derived from an MRI-based PET processing pipeline (ADNI, thresholds of \u3e20/\u3e18 Centiloids for FBP/FBB). Finally, within the ADNI dataset, we tested the linear associations between rPOP- and MRI-based Centiloid values. rPOP achieved accurate warping for N = 2,233/2,258 (98.9%) in the first pass. Of the N = 25 warping failures, 24 were rescued with manual reorientation and origin reset prior to warping. We observed high concordance between rPOP-based amyloid status and both visual reads (IDEAS-BHR, Cohen\u27s k = 0.72 [0.7–0.74], ∼86% concordance) or MRI-pipeline based amyloid status (ADNI, k = 0.88 [0.87–0.89], ∼94% concordance). rPOP- and MRI-pipeline based Centiloids were strongly linearly related (R2:0.95, p\u3c0.001), with this association being significantly modulated by estimated PET resolution (β= -0.016, p\u3c0.001). rPOP provides reliable MRI-free amyloid-PET warping and quantification, leveraging widely available software and only requiring an attenuation-corrected amyloid-PET image as input. The rPOP pipeline enables the comparison and merging of heterogeneous datasets and is publicly available at https://github.com/leoiacca/rPO

Virological and immunological outcome of treatment interruption in HIV-1-infected subjects vaccinated with MVA-B

The most relevant endpoint in therapeutic HIV vaccination is the assessment of time to viral rebound or duration of sustained control of low-level viremia upon cART treatment cessation. Structured treatment interruptions (STI) are however not without risk to the patient and reliable predictors of viral rebound/control after therapeutic HIV-1 vaccination are urgently needed to ensure patient safety and guide therapeutic vaccine development. Here, we integrated immunological and virological parameters together with viral rebound dynamics after STI in a phase I therapeutic vaccine trial of a polyvalent MVA-B vaccine candidate to define predictors of viral control. Clinical parameters, proviral DNA, host HLA genetics and measures of humoral and cellular immunity were evaluated. A sieve effect analysis was conducted comparing pre-treatment viral sequences to breakthrough viruses after STI. Our results show that a reduced proviral HIV-1 DNA at study entry was independently associated with two virological parameters, delayed HIV-1 RNA rebound (p = 0.029) and lower peak viremia after treatment cessation (p = 0.019). Reduced peak viremia was also positively correlated with a decreased number of HLA class I allele associated polymorphisms in Gag sequences in the rebounding virus population (p = 0.012). Our findings suggest that proviral DNA levels and the number of HLA-associated Gag polymorphisms may have an impact on the clinical outcome of STI. Incorporation of these parameters in future therapeutic vaccine trials may guide refined immunogen design and help conduct safer STI approaches