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Abstract Objective The stroke risk for persons living with human immunodeficiency virus (PLHIVs) doubled compared to uninfected individuals. Stroke‐unit (SU)—access, acute reperfusion therapy—use and outcome data on PLHIVs admitted for acute ischemic stroke (AIS) are scarce. Methods AIS patients admitted (01 January 2017 to 31 January 2021) to 10 representative Paris‐area SUs were screened retrospectively from the National Hospitalization Database. PLHIVs were compared to age‐, initial NIHSS‐ and sex‐matched HIV‐uninfected controls (HUCs). Outcome was the 90‐day modified Rankin Scale score. Results Among 126 PLHIVs with confirmed first‐ever AIS, ~80% were admitted outside the thrombolysis‐administration window. Despite antiretrovirals, uncontrolled plasma HIV loads exceeded 50 copies/mL (26% of all PLHIVs; 38% of those ≤55 years). PLHIVs' stroke causes by decreasing frequency were large artery atherosclerosis (LAA), undetermined, other cause, cerebral small‐vessel disease (CSVD) or cardioembolism. No stroke etiology was associated with HIV duration or detectable HIVemia. MRI revealed previously unknown AIS in one in three PLHIVs, twice the HUC rate (p = 0.006). Neither group had optimally controlled modifiable cardiovascular risk factors (CVRFs): 20%–30% without specific hypertension, diabetes, and/or dyslipidemia treatments. Their stroke outcomes were comparable. Multivariable analyses retained good prognosis associated solely with initial NIHSS or reperfusion therapy. Older age and hypertension were associated with CSVD/LAA for all PLHIVs. Standard neurovascular care and reperfusion therapy were well‐tolerated. Interpretation The high uncontrolled HIV‐infection rate and suboptimal CVRF treatment support heightened vigilance to counter suboptimal HIV suppression and antiretroviral adherence, and improve CVRF prevention, mainly for younger PLHIVs. Those preventive, routine measures could lower PLHIVs' AIS risk.

Student recruitment is an increasingly important topic and a major challenge for engineering schools all over Europe, which have difficulties in attracting and enrolling gifted students. On the contrary, French graduate engineering schools attract the most talented students of the nation. What are the forces at play? The aim of this paper is to investigate the decision-making processes behind the students' choice of engineering school. We carried out 18 semi-directive interviews with engineering students of three French graduate engineering schools and completed content analysis of our data. Based on the findings, we identified various individual, social, economic and institutional factors influencing the students' choice of engineering school. The findings indicate that the pre-university model (preparatory classes) has a key influence on engineering schools' recruitment process for attracting talented students.

The DD, TT and DT neutron streaming experiments (NEXP-STRE) in the fusion facility JET are here simulated with TRIPOLI-4® Monte-Carlo code. Specifically, we present the results from the simulation of the DD (2019) and the later TT and DT (2021) campaigns. The last version of TRIPOLI-4® code, developed by CEA, is provided with an innovative variance reduction technique based on the adaptive multi-level splitting (AMS) methodology for particle transport which ensures reliable results in very detailed, complex and vast geometry. Furthermore, a specific tool, developed by CEA, is used to automatically convert MCNP geometry into TRIPOLI-4® geometry format, which allows to perform fast and reliable comparisons between the results obtained by the mean of both calculation tools. The JET 360° MCNP model is used as a basis for creating the TRIPOLI-4® geometry. The neutron flux and doses in thermoluminescent detectors (TLDs) and reaction rates in activation foil (AF) detectors are computed for various positions in the experimental hall. A comparison of our results with the experimental values (2019 DD - 2021 TT campaigns) and the MCNP computed values (all campaigns) is presented. The AMS results crucial for obtaining statistically reliable quantities with TRIPOLI-4® code.

We tested independently the influences of increasing temperature and decreasing moisture on life history and physiological traits in the arthropod Armadillidium vulgare. Both increasing temperature and decreasing moisture led reproductive success to decrease. While the density of immune cells decreased and the β-galactosidase activity increased with increasing temperature and decreasing moisture, which suggests a negative impact of these stressors on individual performance, increased temperature and decreased moisture affected differently the other biomarkers conjuring different underlying mechanisms depending on the stress applied. Our findings demonstrate overall a negative impact of high temperature and low moisture on woodlouse welfare. Changing temperature or moisture had slightly different effects, illustrating the need to test further the respective role of each of these key components of climate change on organisms to predict more reliably the future of our ecosystems.

PURPOSE:To compare peripapillary retinal nerve-fiber-layer (pRNFL) thickness, total retina macular volume, and ganglion-cell-layer (GCL) macular volume and thickness between persons living with HIV (PLHIVs) with well-controlled infections and good immune recovery, and sex- and age-matched HIV-uninfected controls (HUCs). METHODS:This prospective cross-sectional study (www.clinicaltrials.gov identifier: NCT02003989) included 56 PLHIVs, infected for ≥10 [median 20.2] years and with sustained plasma HIV-load suppression on combined antiretroviral therapy (cART) for ≥5 years, and 56 matched HUCs. Participants underwent spectral-domain optical coherence tomography (SD-OCT) with thorough ophthalmological examinations and brain magnetic resonance imaging (MRI). Their overall and quadrant pRNFL thicknesses, total macular volumes, and GCL macular volumes and thicknesses were compared. Cerebral small-vessel diseases (CSVD) complied with STRIVE criteria. RESULTS:Median [interquartile range, IQR] ages of PLHIVs and HUCs, respectively, were 52 [46-60] and 52 [44-60] years. Median [IQR] PLHIVs' nadir CD4+ T-cell count and current CD4/CD8 T-cell ratio were 249/μL [158-350] and 0.95 [0.67-1.10], respectively; HIV-seropositivity duration was 20.2 [15.9-24.5] years; cART duration was 16.8 [12.6-18.6] years; and aviremia duration was 11.4 [7.8-13.6] years. No significant between-group pRNFL thickness, total macular volume, macular GCL-volume and -thickness differences were found. MRI-detected CSVD in 21 (38%) PLHIVs and 14 (25%) HUCs was associated with overall thinner pRNFLs, and smaller total retina and GCL macular volumes, independently of HIV status. CONCLUSIONS:SD-OCT could not detect pRNFL thinning or macular GCL-volume reduction in well-sustained, aviremic, cART-treated PLHIVs who achieved good immune recovery. However, CSVD was associated with thinner pRNFLs and GCLs, independently of HIV status.

[This corrects the article DOI: 10.1371/journal.pone.0229977.].

PURPOSE:To use and test a new method of inducing endogenously generated pupillary oscillations (POs) in patients with unilateral optic neuritis (ON), to describe a signal analysis approach quantifying pupil activity and to evaluate the extent to which POs permit to discriminate patients from control participants. METHOD:Pupil size was recorded with an eye-tracker and converted in real time to modulate the luminance of a stimulus (a 20° disk) presented in front of participants. With this biofeedback setting, an increasing pupil size transforms into a high luminance, entraining a pupil constriction that in turn decreases the stimulus luminance, and so on, resulting in endogenously generated POs. POs were recorded for 30 seconds in the affected eye, in the fellow eye and in binocular conditions with 22 patients having a history of unilateral ON within a period of 5 years, and with 22 control participants. Different signal analysis methods were used to quantify the power and frequency of POs. RESULTS:On average, pupil size oscillated at around 1 Hz. The amplitude of POs appears not to be a reliable marker of ON. In contrast, the frequency of POs was significantly lower, and was more variable over time, in the patients' affected eye, as compared to their fellow eye and to the binocular condition. No such differences were found in control participants. Receiver operating characteristic analyses based on the frequency and the variability of POs to classify patients and control participants gave an area under the curve of 0.82, a sensitivity of 82% (95%CI: 60%-95%) and a specificity of 77% (95%CI: 55%-92%). CONCLUSIONS:The new method used to induce POs allowed characterizing the visual afferent pathway defect in ON patients with encouraging accuracy. The method was fast, easy to use, only requiring that participants look ahead, and allows testing many stimulus parameters (e.g. color, stimulus location, size, etc).

Leber's hereditary optic neuropathy (LHON) is a maternally inherited blinding disorder, which in over 90% of cases is due to one of three primary mitochondrial DNA (mtDNA) point mutations (m.11778G>A, m.3460G>A and m.14484T>C, respectively in MT-ND4, MT-ND1 and MT-ND6 genes). However, the spectrum of mtDNA mutations causing the remaining 10% of cases is only partially and often poorly defined.In order to improve such a list of pathological variants, we completely sequenced the mitochondrial genomes of suspected LHON patients from Italy, France and Germany, lacking the three primary common mutations. Phylogenetic and conservation analyses were performed. Sixteen mitochondrial genomes were found to harbor at least one of the following nine rare LHON pathogenic mutations in genes MT-ND1 (m.3700G>A/p.A132T, m.3733G>A-C/p.E143K-Q, m.4171C>A/p.L289M), MT-ND4L (m.10663T>C/p.V65A) and MT-ND6 (m.14459G>A/p.A72V, m.14495A>G/p.M64I, m.14482C>A/p.L60S, and m.14568C>T/p.G36S). Phylogenetic analyses revealed that these substitutions were due to independent events on different haplogroups, whereas interspecies comparisons showed that they affected conserved amino acid residues or domains in the ND subunit genes of complex I.Our findings indicate that these nine substitutions are all primary LHON mutations. Therefore, despite their relative low frequency, they should be routinely tested for in all LHON patients lacking the three common mutations. Moreover, our sequence analysis confirms the major role of haplogroups J1c and J2b (over 35% in our probands versus 6% in the general population of Western Europe) and other putative synergistic mtDNA variants in LHON expression.

Background and purpose: Middle‐aged persons living with HIV (PLHIV) have a heightened risk of more concomitant age‐related comorbidities that are acknowledged as signs of poorer prognosis after deep‐brain stimulation of the subthalamic nucleus (STN‐DBS) at younger‐than‐expected ages. To assess the beneficial and adverse effects of STN‐DBS in PLHIV with Parkinson's disease (PD). Methods: We retrospectively included nine PLHIV with PD who had sustained virological control. Patients were followed up for 7 ± 4 years. Results: Patients' mean ages at PD onset and STN‐DBS were 45 ± 15 and 53 ± 16 years, respectively. At STN‐DBS, mean HIV infection and PD durations were 15 ± 12 and 8 ± 4 years, respectively. STN‐DBS significantly improved 1‐year Unified Parkinson's Disease Rating Scale (UPDRS)‐III scores (71%), daily off‐time (63%), motor fluctuations (75%) and daily levodopa‐equivalent dose (68%); mean 5‐year UPDRS‐III score and motor fluctuation improvements remained ~45%. Impulse control disorders (affecting 6/9 patients) fully resolved after STN‐DBS. Postoperative course was uneventful. No serious adverse events occurred during follow‐up. Conclusion: Our findings indicate that STN‐DBS is a safe and effective treatment for PLHIV with PD. [ABSTRACT FROM AUTHOR]

Objective: Restoring anti‐JC virus (JCV) immunity is the only treatment of progressive multifocal leukoencephalopathy (PML). Interleukin‐7 is a cytokine that increases number and function of T cells. We analyzed a population of PML patients who received recombinant human IL‐7 (rhIL‐7) to estimate survival and its determinants. Methods: After exclusion of patients with missing data or receiving other immunotherapies, findings from 64 patients with proven PML who received rhIL‐7 between 2007 and 2020 were retrospectively analyzed. Logistic regression was used to analyze variables associated with one‐year survival. Results: Underlying conditions were HIV/AIDS (n = 27, 42%), hematological malignancies (n = 16, 25%), primary immunodeficiencies (n = 13, 20%), solid organ transplantation (n = 4, 6%) and chronic inflammatory diseases (n = 4, 6%). One‐year survival was 54.7% and did not differ by underlying condition. Survival was not associated with baseline characteristics, but with a >50% increase in blood lymphocytes (OR 4.1, 95%CI 1.2–14.9) and CD4+ T cells (OR 5.9, 95%CI 1.7–23.3), and a > 1 log copies/mL decrease in cerebrospinal fluid JCV DNA (OR 7.6, 95%CI 1.6–56.1) during the first month after rhIL‐7 initiation. Side effects were mainly local and flu‐like symptoms (n = 8, 12.5%) and PML‐immune reconstitution inflammatory syndrome (IRIS) (n = 5, 8%). Interpretation: In this non‐controlled retrospective study, survival did not differ from that expected in HIV/AIDS patients, but might have been improved in those with hematological malignancies, primary immunodeficiencies and transplant recipients. RhIL‐7 might have contributed to the increase in blood lymphocytes and decrease in CSF JCV replication that were associated with better survival. ANN NEUROL 2022;91:496–505 [ABSTRACT FROM AUTHOR]