Correlation between CD4/CD8 ratio and neurocognitive performance during early HIV infection

INTRODUCTION: CD4/CD8 ratio is a marker of immune activation in HIV infection and has been associated with neurocognitive performance during chronic infection, but little is known about the early phases. The aim of this study was to examine the relationship between blood CD4/CD8 ratio and central nervous system endpoints in primary HIV infection (PHI) before and after antiretroviral treatment (ART). METHODS: This was a retrospective analysis of the Primary Infection Stage CNS Events Study (PISCES) cohort. We longitudinally assessed blood and cerebrospinal fluid (CSF) markers of inflammation, immune activation and neuronal injury, and neuropsychological testing performance (NPZ4, an average of three motor and one processing speed tests, and a summarized total score, NPZ11, including also executive function, learning and memory) in ART-naïve participants enrolled during PHI. Spearman correlation and linear mixed models assessed the relationships between the trajectory of CD4/CD8 ratio over time and neurocognitive performance, blood and CSF markers of immune activation and neuronal injury. RESULTS: In all, 109 PHI participants were enrolled. The mean CD4/CD8 ratio decreased with longer time from infection to starting treatment (p < 0.001). Every unit increase in NPZ4 score was independently associated with a 0.15 increase in CD4/CD8 ratio (95% CI: 0.002-0.29; p = 0.047), whereas no correlation was found between CD4/CD8 ratio and NPZ11. Among the cognitive domains, only a change in processing speed was correlated with CD4/CD8 ratio over time (p = 0.03). The trajectory of the CD4/CD8 ratio was negatively correlated with change in CSF neurofilament light chain (p = 0.04). CONCLUSIONS: The trajectory of CD4/CD8 ratio was independently associated with motor/psychomotor speed performance, suggesting that immune activation is involved in brain injury during the early stages of the infection

User-centered design and development of TWIN-Acta: A novel control suite of the TWIN lower limb exoskeleton for the rehabilitation of persons post-stroke

Introduction: Difficulties faced while walking are common symptoms after stroke, significantly reducing the quality of life. Walking recovery is therefore one of the main priorities of rehabilitation. Wearable powered exoskeletons have been developed to provide lower limb assistance and enable training for persons with gait impairments by using typical physiological movement patterns. Exoskeletons were originally designed for individuals without any walking capacities, such as subjects with complete spinal cord injuries. Recent systematic reviews suggested that lower limb exoskeletons could be valid tools to restore independent walking in subjects with residual motor function, such as persons post-stroke. To ensure that devices meet end-user needs, it is important to understand and incorporate their perspectives. However, only a limited number of studies have followed such an approach in the post-stroke population. Methods: The aim of the study was to identify the end-users needs and to develop a user-centered-based control system for the TWIN lower limb exoskeleton to provide post-stroke rehabilitation. We thus describe the development and validation, by clinical experts, of TWIN-Acta: a novel control suite for TWIN, specifically designed for persons post-stroke. We detailed the conceived control strategy and developmental phases, and reported evaluation sessions performed on healthy clinical experts and people post-stroke to evaluate TWIN-Acta usability, acceptability, and barriers to usage. At each developmental stage, the clinical experts received a one-day training on the TWIN exoskeleton equipped with the TWIN-Acta control suite. Data on usability, acceptability, and limitations to system usage were collected through questionnaires and semi-structured interviews. Results: The system received overall good usability and acceptability ratings and resulted in a well-conceived and safe approach. All experts gave excellent ratings regarding the possibility of modulating the assistance provided by the exoskeleton during the movement execution and concluded that the TWIN-Acta would be useful in gait rehabilitation for persons post-stroke. The main limit was the low level of system learnability, attributable to the short-time of usage. This issue can be minimized with prolonged training and must be taken into consideration when planning rehabilitation. Discussion: This study showed the potential of the novel control suite TWIN-Acta for gait rehabilitation and efficacy studies are the next step in its evaluation process

Long-Term Drug Survival and Effectiveness of Secukinumab in Patients with Moderate to Severe Chronic Plaque Psoriasis: 42-Month Results from the SUPREME 2.0 Study

Purpose: SUPREME, a phase IIIb study conducted in Italy, demonstrated safety and high efficacy of secukinumab for up to 72 weeks in patients with moderate-to-severe plaque-type psoriasis. SUPREME 2.0 study aimed to provide real-world data on the long-term drug survival and effectiveness of secukinumab beyond 72 weeks. Patients and Methods: SUPREME 2.0 is a retrospective observational chart review study conducted in patients previously enrolled in SUPREME study. After the end of the SUPREME study, eligible patients continued treatment as per clinical practice, and their effectiveness and drug survival data were retrieved from medical charts. Results: Of the 415 patients enrolled in the SUPREME study, 297 were included in SUPREME 2.0; of which, 210 (70.7%) continued secukinumab treatment throughout the 42-month observation period. Patients in the biologic-naïve cohort had higher drug survival than those in the biologic-experienced cohort (74.9% vs 61.7%), while HLA-Cw6–positive and HLA-Cw6–negative patients showed similar drug survival (69.3% and 71.9%). After 42 months, Psoriasis Area and Severity Index (PASI) 90 was achieved by 79.6% of patients overall; with a similar proportion of biologic-naïve and biologic-experienced patients achieving PASI90 (79.8% and 79.1%). The mean absolute PASI score reduced from 21.94 to 1.38 in the overall population, 21.90 to 1.24 in biologic-naïve and 22.03 to 1.77 in biologic-experienced patients after 42 months. The decrease in the absolute PASI score was comparable between HLACw6–positive and HLA–Cw6-negative patients. The baseline Dermatology Life Quality Index scores also decreased in the overall patients (10.5 to 2.32) and across all study sub-groups after 42 months. Safety was consistent with the known profile of secukinumab, with no new findings. Conclusion: In this real-world cohort study, secukinumab showed consistently high long-term drug survival and effectiveness with a favourable safety profile

MAVIS: The adaptive optics module feasibility study

The Adaptive Optics Module of MAVIS is a self-contained MCAO module, which delivers a corrected FoV to the postfocal scientific instruments, in the visible. The module aims to exploit the full potential of the ESO VLT UT4 Adaptive Optics Facility, which is composed of the high spatial frequency deformable secondary mirror and the laser guide stars launching and control systems. During the MAVIS Phase A, we evaluated, with the support of simulations and analysis at different levels, the main terms of the error budgets aiming at estimating the realistic AOM performance. After introducing the current opto-mechanical design and AO scheme of the AOM, we here present the standard wavefront error budget and the other budgets, including manufacturing, alignment of the module, thermal behavior and noncommon path aberrations, together with the contribution of the upstream telescope system

Smaller limbic structures are associated with greater immunosuppression in over 1000 HIV-infected adults across five continents: Findings from the ENIGMA-HIV Working Group

Background: Human immunodeficiency virus type-1 (HIV) infection can be controlled with combination antiretroviral therapy (cART), but neurocognitive impairment remains common even in chronic and treated HIV-infected (HIV+) cohorts. Identifying the neuroanatomical pathways associated with infection has the potential to delineate novel neuropathological processes underlying persisting deficits, yet individual neuroimaging studies have yielded inconsistent findings. The ENIGMA-HIV Working Group was established to harmonize data from diverse studies to identify the common effects of HIV-infection on brain structure. Methods: Data were pooled from 12 independent neuroHIV studies from Africa, Asia, Australia, Europe, and North America. Volume estimates for eight subcortical brain regions were extracted from T1-weighted MRI from 1,044 HIV+ adults (aged 22-81 years; 72.4% on cART; 70.3% male; 41.6% with detectable viral load (dVL)), to identify associations with plasma markers reflecting current immunosuppression (CD4+ T-cell count) or dVL. Follow-up analyses stratified data by cART status and sex. Bonferroni correction was used to determine statistical significance. Findings: LowercurrentCD4+ count was associated with smaller hippocampal (β= 20.3 mm3 per 100 cells/mm3; p = 0.0001) and thalamic volumes (β= 29.3; p = 0.003); in the subset of participants not on cART, it was associated with smaller putamen volumes (β= 65.1; p = 0.0009). On average, a dVL was associated with smaller hippocampal (Cohen’s d = 0.24; p = 0.0003) and amygdala volumes (d = 0.18; p = 0.0058).Interpretation: In HIV+ individuals across five continents, smaller limbic volumes were consistently associated with current plasma markers. As we assessed cohorts with different inclusion/exclusion criteria and demographic distributions, these deficits may represent a generalizable brain-signature of HIV infection in the cART era. Our findings support the importance of achieving viral suppression and immune restoration for maintaining brain health. Funding: This work was supported, in part, by NIH grant U54 EB020403

Association of Immunosuppression and Viral Load With Subcortical Brain Volume in an International Sample of People Living With HIV

International audienceIMPORTANCE Despite more widely accessible combination antiretroviral therapy (cART), HIV-1 infection remains a global public health challenge. Even in treated patients with chronic HIV infection, neurocognitive impairment often persists, affecting quality of life. Identifying the neuroanatomical pathways associated with infection in vivo may delineate the neuropathologic processes underlying these deficits. However, published neuroimaging findings from relatively small, heterogeneous cohorts are inconsistent, limiting the generalizability of the conclusions drawnto date.OBJECTIVE To examine structural brain associations with the most commonly collected clinicalassessments of HIV burden (CD4+T-cell count and viral load), which are generalizable acrossdemographically and clinically diverse HIV-infected individuals worldwide.DESIGN, SETTING, AND PARTICIPANTS This cross-sectional study established the HIV WorkingGroup within the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) consortiumto pool and harmonize data from existing HIV neuroimaging studies. In total, data from 1295HIV-positive adults were contributed from 13 studies across Africa, Asia, Australia, Europe, and NorthAmerica. Regional and whole brain segmentations were extracted from data sets as contributingstudies joined the consortium on a rolling basis from November 1, 2014, to December 31, 2019.MAIN OUTCOMES AND MEASURES Volume estimates for 8 subcortical brain regions wereextracted from T1-weighted magnetic resonance images to identify associations with blood plasmamarkers of current immunosuppression (CD4+T-cell counts) or detectable plasma viral load (dVL) inHIV-positive participants. Post hoc sensitivity analyses stratified data by cART status.RESULTS After quality assurance, data from 1203 HIV-positive individuals (mean [SD] age, 45.7 [11.5]years; 880 [73.2%] male; 897 [74.6%] taking cART) remained. Lower current CD4+cell counts wereassociated with smaller hippocampal (mean [SE] β = 16.66 [4.72] mm3per 100 cells/mm3;P< .001)and thalamic (mean [SE] β = 32.24 [8.96] mm3per 100 cells/mm3;P< .001) volumes and largerventricles (mean [SE] β = −391.50 [122.58] mm3per 100 cells/mm3;P= .001); in participants nottaking cART, however, lowercurrent CD4+cell counts were associated with smaller putamen volumes(mean [SE] β = 57.34 [18.78] mm3per 100 cells/mm3;P= .003). A dVL was associated with smallerhippocampal volumes (d= −0.17;P= .005); in participants taking cART, dVL was also associated withsmaller amygdala volumes (d= −0.23;P= .004

An Empirical Analysis on Board Monitoring Role and Loan Portfolio Quality Measurement in Banks

This paper aims to analyze the effectiveness of the board monitoring role on specific loan portfolio quality measures in banks (default rate, recovery rate and provisioning rate). We use a sample comprises a totality of Italian-based banks, listed at Borsa Italiana SpA in 2006-2008 and a number of accounting proxies to express the loan portfolio quality of a bank. The results of the analysis show an overall weakness of the board role (expressed by Independents and Audit Committee on board) in monitoring loan portfolio quality of the bank, with the subsequent damage of the interests of stakeholders. A positive contribution of board monitoring, even if partial, is highlighted in two cases: Independents seems improve recovery rate, while the Audit committee enhances provisioning rate in banks. With reference to default rate, a total negative effect of board monitoring is reported. On the base of these results, some managerial implications are proposed