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Abstract Objective As part of a research aiming at presenting an alternative approach for rapid determination of antimicrobial susceptibility by quantification of changes in expression levels of specific marker genes and gene sets, cultures of the virulent bacterial strain Francisella tularensis SchuS4 were grown in the presence of inhibitory/sub-inhibitory concentrations of either ciprofloxacin or doxycycline and their transcriptomic profiles were elucidated using differential expression analysis followed by functional annotation. Data description RNA sequencing was performed to identify differentially expressed genes (DEGs) in response to exposure of F. tularensis SchuS4 to either ciprofloxacin or doxycycline, the antibiotics of choice for Tularemia therapy. Accordingly, RNA samples were collected 2 h post antibiotic exposure and subjected to RNA sequence analysis. Transcriptomic quantification of RNA representing duplicated samples generated highly similar gene expression data. Exposure to sub-inhibitory concentration [0.5 x MIC (minimal inhibitory concentration)] of doxycycline or ciprofloxacin modulated the expression of 237 or 8 genes, respectively, while exposure to an inhibitory concentration (1 x MIC) resulted in the modulation of 583 or 234 genes, respectively. Amongst the genes modulated upon doxycycline exposure upregulation of 31 genes encoding for translation-functions could be distinguished, as well as downregulation of 14 genes encoding for functions involved in DNA transcription and repair. Ciprofloxacin exposure impacted differently the RNA sequence profile of the pathogen, resulting in upregulation of 27 genes encoding mainly DNA replication and repair functions, transmembrane transporters and molecular chaperons. In addition, 15 downregulated genes were involved in translation processes.

Abstract Objective As part of a research aiming at the isolation of bacteria secreting growth inhibiting compounds, cultures of Francisella tularensis were implanted in environmental samples and monitored for inhibition zones on agar. Two antibiotic-like secreting bacteria were isolated, their genomic sequence was deciphered and taxonomic profiling analysis classified them as belonging to the Pantoea genus. Data description Two bacterial isolates exhibiting growth inhibition zones to F. tularensis (LVS) were analyzed using the Oxford Nanopore Technology (ONT). Preliminary de novo assembly of the reads was performed, followed by taxonomic profiling based on Multi Locus Sequence Analysis (MLSA) and implementation of the Average Nucleotide Identity (ANI) measure. The genomic sequences resulted in the identification of two different Pantoea species, denoted EnvD and EnvH. Subsequent de novo genome assembly generated 5 and 10 contigs for EnvD and EnvH, respectively. The largest contig (4,008,183 bps and 3,740,753 bps for EnvD and EnvH, respectively), overlaps to a major extent to the chromosome of closely related Pantoea species. ANI values calculated for both isolates revealed two apparently new species of the Pantoea genus. Our study deciphered the identity of two bacteria producing antibiotic-like compounds, and the genomic sequence revealed they represent distinct Pantoea species.

Great efforts are being made to develop new rapid antibiotic susceptibility tests to meet the demand for clinical relevance versus disease progression. This is important especially in diseases caused by bacteria such as Yersinia pestis, the causative agent of plague, which grows rapidly in vivo but relatively slow in vitro. This compromises the ability to use standard growth-based susceptibility tests to obtain rapid and proper antibiotic treatment guidance. Using our previously described platform of quantifying antibiotic-specific transcriptional changes, we developed a molecular test based on changes in expression levels of doxycycline response-dependent marker genes that we identified by transcriptomic analysis. This enabled us to determine the minimal inhibitory concentration of doxycycline within 7 h compared to the 24 h required by the standard CLSI test. This assay was validated with various Y. pestis strains. Moreover, we demonstrated the applicability of the molecular test, combined with a new rapid bacterial isolation step from blood cultures, and show its relevance as a rapid test in clinical settings.

Pneumonic plague is an infectious disease characterized by rapid and fulminant development of acute pneumonia and septicemia that results in death within days of exposure. The causative agent of pneumonic plague, Yersinia pestis (Y. pestis), is a Tier-1 bio-threat agent. Parenteral antibiotic treatment is effective when given within a narrow therapeutic window after symptom onset. However, the non-specific “flu-like” symptoms often lead to delayed diagnosis and therapy. In this study, we evaluated inhalational gentamicin therapy in an infected mouse model as a means to improve antibiotic treatment efficacy. Inhalation is an attractive route for treating lung infections. The advantages include directly dosing the main infection site, the relative accessibility for administration and the lack of extensive enzymatic drug degradation machinery. In this study, we show that inhalational gentamicin treatment administered 24 h post-infection, prior to the appearance of symptoms, protected against lethal intranasal challenge with the fully virulent Y. pestis Kimberley53 strain (Kim53). Similarly, a high survival rate was demonstrated in mice treated by inhalation with another aminoglycoside, tobramycin, for which an FDA-approved inhaled formulation is clinically available for cystic fibrosis patients. Inhalational treatment with gentamicin 48 h post-infection (to symptomatic mice) was also successful against a Y. pestis challenge dose of 10 i.n.LD50. Whole-body imaging using IVIS technology demonstrated that adding inhalational gentamicin to parenteral therapy accelerated the clearance of Y. pestis from the lungs of infected animals. This may reduce disease severity and the risk of secondary infections. In conclusion, our data suggest that inhalational therapy with aerosolized gentamicin may be an effective prophylactic treatment against pneumonic plague. We also demonstrate the benefit of combining this treatment with a conventional parenteral treatment against this rapidly progressing infectious disease. We suggest the inhalational administration route as a clinically relevant treatment modality against pneumonic plague and other respiratory bacterial pathogens.

Abstract A social individual needs to effectively manage the amount of complex information in his or her environment relative to his or her own purpose to obtain relevant information. This paper presents a neural architecture aiming to reproduce attention mechanisms (alerting/orienting/selecting) that are efficient in humans during audiovisual tasks in robots. We evaluated the system based on its ability to identify relevant sources of information on faces of subjects emitting vowels. We propose a developmental model of audio-visual attention (MAVA) combining Hebbian learning and a competition between saliency maps based on visual movement and audio energy. MAVA effectively combines bottom-up and top-down information to orient the system toward pertinent areas. The system has several advantages, including online and autonomous learning abilities, low computation time and robustness to environmental noise. MAVA outperforms other artificial models for detecting speech sources under various noise conditions.

Background and objectivesUp to 46% of patients with presumed autoimmune limbic encephalitis are seronegative for all currently known central nervous system (CNS) antigens. We developed a cell-based assay (CBA) to screen for novel neural antibodies in serum and cerebrospinal fluid (CSF) using neurons and astrocytes derived from human-induced pluripotent stem cells (hiPSCs).MethodsHuman iPSC-derived astrocytes or neurons were incubated with serum/CSF from 99 patients [42 with inflammatory neurological diseases (IND) and 57 with non-IND (NIND)]. The IND group included 11 patients with previously established neural antibodies, six with seronegative neuromyelitis optica spectrum disorder (NMOSD), 12 with suspected autoimmune encephalitis/paraneoplastic syndrome (AIE/PNS), and 13 with other IND (OIND). IgG binding to fixed CNS cells was detected using fluorescently-labeled antibodies and analyzed through automated fluorescence measures. IgG neuronal/astrocyte reactivity was further analyzed by flow cytometry. Peripheral blood mononuclear cells (PBMCs) were used as CNS-irrelevant control target cells. Reactivity profile was defined as positive using a Robust regression and Outlier removal test with a false discovery rate at 10% following each individual readout.ResultsUsing our CBA, we detected antibodies recognizing hiPSC-derived neural cells in 19/99 subjects. Antibodies bound specifically to astrocytes in nine cases, to neurons in eight cases, and to both cell types in two cases, as confirmed by microscopy single-cell analyses. Highlighting the significance of our comprehensive 96-well CBA assay, neural-specific antibody binding was more frequent in IND (15 of 42) than in NIND patients (4 of 57) (Fisher’s exact test, p = 0.0005). Two of four AQP4+ NMO and four of seven definite AIE/PNS with intracellular-reactive antibodies [1 GFAP astrocytopathy, 2 Hu+, 1 Ri+ AIE/PNS)], as identified in diagnostic laboratories, were also positive with our CBA. Most interestingly, we showed antibody-reactivity in two of six seronegative NMOSD, six of 12 probable AIE/PNS, and one of 13 OIND. Flow cytometry using hiPSC-derived CNS cells or PBMC-detected antibody binding in 13 versus zero patients, respectively, establishing the specificity of the detected antibodies for neural tissue.ConclusionOur unique hiPSC-based CBA allows for the testing of novel neuron-/astrocyte-reactive antibodies in patients with suspected immune-mediated neurological syndromes, and negative testing in established routine laboratories, opening new perspectives in establishing a diagnosis of such complex diseases.

Abstract Background To describe and analyze the real-life refractive, functional and safety outcomes of the Clareon® intraocular lens (IOL) after 3 years. Methods Data was collected retrospectively for observational purposes between July 2017 and December 2019 in the ophthalmology department of Desgenettes military hospital in Lyon, France. Eyes that underwent cataract surgery with Claeron® implantation were consecutively included. Patients with a systemic or ocular condition that could affect the visual outcome were excluded. Postoperative corrected (CDVA) and uncorrected (UDVA) distance visual acuities as well as capsule and IOL transparency were assessed at 1 month and 3 years. Results A total of 326 eyes were analyzed at one month and 191 eyes were reassessed at the 3-year follow-up visit. At 3 years, the mean CDVA was 0.003 LogMAR (95% confidence interval [CI]: -0.003 to -0.01) and the mean UDVA was 0.075 (95% CI: 0.054 to 0.095). Three quarters of the patients had an UDVA ≥ 0.097 logMAR (20/25 Snellen equivalent) and 50% had an UDVA ≥ 0 (20/20). The absence of glistening was reported in 95.3% of cases and 4.7% [9] of patients experienced a clinically significant posterior capsular opacification (PCO) for which Nd:YAG treatment was required. Conclusions This real-life study reports high-performance and stable long-term refractive outcomes of the Clareon® IOL with good safety in terms of PCO and glistening.

Questo contributo riassume i risultati relativi al transfer positivo. Alcune delle tesi presenti nel concetto generale delle lingue sono confermate dalle scienze dell’apprendimento e dalla ricerca in ambito di apprendimento e didattica delle lingue, che da una parte fornisce una risposta a domande rilevanti, ma che dall’altra ne solleva delle nuove. Infine vengono discusse alcune problematiche che dovrebbero essere ricercate in maniera più approfondita, così che i nuovi curricula multilingui possano essere modellati sulla base di evidenze scientifiche.

Abstract Brain circuits display modular architecture at different scales of organization. Such neural assemblies are typically associated to functional specialization but the mechanisms leading to their emergence and consolidation still remain elusive. In this paper we investigate the role of inhibition in structuring new neural assemblies driven by the entrainment to various inputs. In particular, we focus on the role of partially synchronized dynamics for the creation and maintenance of structural modules in neural circuits by considering a network of excitatory and inhibitory $$\theta$$ θ -neurons with plastic Hebbian synapses. The learning process consists of an entrainment to temporally alternating stimuli that are applied to separate regions of the network. This entrainment leads to the emergence of modular structures. Contrary to common practice in artificial neural networks—where the acquired weights are typically frozen after the learning session—we allow for synaptic adaptation even after the learning phase. We find that the presence of inhibitory neurons in the network is crucial for the emergence and the post-learning consolidation of the modular structures. Indeed networks made of purely excitatory neurons or of neurons not respecting Dale’s principle are unable to form or to maintain the modular architecture induced by the stimuli. We also demonstrate that the number of inhibitory neurons in the network is directly related to the maximal number of neural assemblies that can be consolidated, supporting the idea that inhibition has a direct impact on the memory capacity of the neural network.

Summary: Background: Pharmacological synergisms are an attractive anticancer strategy. However, with more than 5000 approved-drugs and compounds in clinical development, identifying synergistic treatments represents a major challenge. Methods: High-throughput screening was combined with target deconvolution and functional genomics to reveal targetable vulnerabilities in glioblastoma. The role of the top gene hit was investigated by RNA interference, transcriptomics and immunohistochemistry in glioblastoma patient samples. Drug combination screen using a custom-made library of 88 compounds in association with six inhibitors of the identified glioblastoma vulnerabilities was performed to unveil pharmacological synergisms. Glioblastoma 3D spheroid, organotypic ex vivo and syngeneic orthotopic mouse models were used to validate synergistic treatments. Findings: Nine targetable vulnerabilities were identified in glioblastoma and the top gene hit RRM1 was validated as an independent prognostic factor. The associations of CHK1/MEK and AURKA/BET inhibitors were identified as the most potent amongst 528 tested pairwise drug combinations and their efficacy was validated in 3D spheroid models. The high synergism of AURKA/BET dual inhibition was confirmed in ex vivo and in vivo glioblastoma models, without detectable toxicity. Interpretation: Our work provides strong pre-clinical evidence of the efficacy of AURKA/BET inhibitor combination in glioblastoma and opens new therapeutic avenues for this unmet medical need. Besides, we established the proof-of-concept of a stepwise approach aiming at exploiting drug poly-pharmacology to unveil druggable cancer vulnerabilities and to fast-track the identification of synergistic combinations against refractory cancers. Funding: This study was funded by institutional grants and charities.

Abstract CHD8, a major autism gene, functions in chromatin remodelling and has various roles involving several biological pathways. Therefore, unsurprisingly, previous studies have shown that intellectual developmental disorder with autism and macrocephaly (IDDAM), the syndrome caused by pathogenic variants in CHD8, consists of a broad range of phenotypic abnormalities. We collected and reviewed 106 individuals with IDDAM, including 36 individuals not previously published, thus enabling thorough genotype–phenotype analyses, involving the CHD8 mutation spectrum, characterization of the CHD8 DNA methylation episignature, and the systematic analysis of phenotypes collected in Human Phenotype Ontology (HPO). We identified 29 unique nonsense, 25 frameshift, 24 missense, and 12 splice site variants. Furthermore, two unique inframe deletions, one larger deletion (exons 26–28), and one translocation were observed. Methylation analysis was performed for 13 patients, 11 of which showed the previously established episignature for IDDAM (85%) associated with CHD8 haploinsufficiency, one analysis was inconclusive, and one showing a possible gain-of-function signature instead of the expected haploinsufficiency signature was observed. Consistent with previous studies, phenotypical abnormalities affected multiple organ systems. Many neurological abnormalities, like intellectual disability (68%) and hypotonia (29%) were observed, as well as a wide variety of behavioural abnormalities (88%). Most frequently observed behavioural problems included autism spectrum disorder (76%), short attention span (32%), abnormal social behaviour (31%), sleep disturbance (29%) and impaired social interactions (28%). Furthermore, abnormalities in the digestive (53%), musculoskeletal (79%) and genitourinary systems (18%) were noted. Although no significant difference in severity was observed between males and females, individuals with a missense variant were less severely affected. Our study provides an extensive review of all phenotypic abnormalities in patients with IDDAM and provides clinical recommendations, which will be of significant value to individuals with a pathogenic variant in CHD8, their families, and clinicians as it gives a more refined insight into the clinical and molecular spectrum of IDDAM, which is essential for accurate care and counselling.

This survey investigates teacher and student perceptions and beliefs relating to the use of digital translation tools and online dictionaries (e. g. Google Translate, DeepL, Leo, Pons) in the foreign language classroom. Over the past few years, these tools have become increasingly popular, a development that has given rise to questions about their benefits for foreign language learning and teaching. A total of 1187 participants (985 students and 202 teachers) took part in the study. They came from primary schools, lower and upper secondary schools (Gymnasium and Fachmatura, vocational schools), as well as tertiary education and professional development classes. The survey was conducted in French (n=834) and German (n=353) in the cantons of Bern, Fribourg, Geneva, Jura, Neuchâtel and Solothurn. Participation was voluntary. Results show that regardless of language background and educational context, participants perceive of the tools as a normal and largely established part of their everyday practices. Compared to their teachers, students are more optimistic about the tools’ potential contribution to foreign language learning and less concerned about possible pitfalls linked to using the tools. Students in lower secondary school use digital translation aids less frequently and rate their contribution to language learning and motivation less favourably than the other learner groups. Many teachers would like to use digital translators and online dictionaries in their classroom, but they express uncertainty about how to do so meaningfully. Teachers voice concerns over certain student practices, namely the lack of cognitive involvement when simply translating text without considering the output. Teachers also highlight the gap between curricular/institutional prescriptions and the way the tools are commonly used, a mismatch that can affect their teaching. Overall, our findings emphasize the need for a) empirical evidence on the effects of digital translation tools on foreign language acquisition, b) pedagogical scenarios for implementing the tools, and 3) alignment of policy with practice.

Background: The impact of traumatic brain injury (TBI) on the pediatric population is profound. The aim of this study is to unveil the state of the evidence concerning acute neurosurgical intervention, hospitalizations after injury, and neuroimaging in isolated skull fractures (ISF). Materials and Methods: This systematic review was conducted in accordance with PRISMA guidelines. PubMed, Cochrane, Web of Science, and Embase were searched for papers until April 2023. Only ISF cases diagnosed via computed tomography were considered. Results: A total of 10,350 skull fractures from 25 studies were included, of which 7228 were ISF. For the need of acute neurosurgical intervention, the meta-analysis showed a risk of 0% (95% CI: 0–0%). For hospitalization after injury the calculated risk was 78% (95% CI: 66–89%). Finally, for the requirement of repeated neuroimaging the analysis revealed a rate of 7% (95% CI: 0–15%). No deaths were reported in any of the 25 studies. Conclusions: Out of 7228 children with ISF, an almost negligible number required immediate neurosurgical interventions, yet a significant 74% were hospitalized for up to 72 h. Notably, the mortality was zero, and repeat neuroimaging was uncommon. This research is crucial in shedding light on the outcomes and implications of pediatric TBIs concerning ISFs.

Background: Seizures in the early postoperative period may impair patient recovery and increase the risk of complications. The aim of this study is to determine whether there is any advantage in postoperative seizure prophylaxis following meningioma resection. Methods: This systematic review was conducted in accordance with PRISMA guidelines. PUBMED, Web of Science, Embase, Science Direct, and Cochrane were searched for papers until April 2023. Results: Among nine studies, a total of 3249 patients were evaluated, of which 984 patients received antiepileptic drugs (AEDs). No significant difference was observed in the frequency of seizure events between patients who were treated with antiepileptic drugs (AEDs) and those who were not. (RR 1.22, 95% CI 0.66 to 2.40; I2 = 57%). Postoperative seizures occurred in 5% (95% CI: 1% to 9%) within the early time period (7 days), with significant heterogeneity between the studies (I2 = 91% and 97%, respectively). In seizure-naive patients, the rate of postoperative seizures was 2% (95% CI: 0% to 6%) in the early period and increased to 6% (95% CI: 0% to 15%) in the late period. High heterogeneity led to the use of random-effects models in all analyses. Conclusions: The current evidence does not provide sufficient support for the effectiveness of prophylactic AED medications in preventing postoperative seizures in patients undergoing meningioma resection. This underscores the importance of considering diagnostic criteria and conducting individual patient analysis to guide clinical decision-making in this context.

The objective of this study was to evaluate the frequency of herbaceous species, the availability, and supply of dry matter grass goats layer ended in a caatinga enriched with Urochloa trichopus grass and submitted to three levels of concentrate supplement (0.5%, 1.0%, and 1.5% over the bodyweight) relative to the control group (0.0%). 24 goats were used crossbreed F1 (Boer x non-descript breed) with an average body weight of 27.00 ± 3.32 kg. The experimental area was 2.4 ha, divided into four paddocks of 0.6 ha. The frequency analysis was carried out by the presence or absence of each species in the sample unit, which expresses the ratio of plots where the sample species were present. For quantification of dry matter availability and delivery of fodder, vegetation was separated into Urochloa trichopus grass, other grasses and herbaceous dicots were cut at soil level and weighed. The frequency of herbaceous species in the bush after thinning and enriched with Urochloa trichopus grass is more influenced by environmental conditions (rain) than the treatment of scrub, whatever the level of concentrate supplementation utilized the ratio has been above 48%. In the bush after thinning and enriched with Urochloa trichopus grass, whatever the season, availability of herbaceous components does not change with supplementation, but as they are characterized the dry period, the availability of dry matter of herbaceous vegetation decreases, and litter increases.

In cycling, propulsion is generated by the muscles of the lower limbs and hips. After the first reports of pedal/crank force measurements in the late 1960s, it has been assumed that highly trained athletes have better power transfer to the pedals than recreational cyclists. However, motor patterns indicating higher levels of performance are unknown. To compare leg muscle activation between trained (3.5-4.2 W/kgbw) and highly trained (4.3-5.1 W/kgbw) athletes we applied electromyography, lactate, and bi-pedal/crank force measurements during a maximal power test, an individual lactate threshold test and a constant power test. We show that specific activation patterns of the rectus femoris (RF) and vastus lateralis (VL) impact on individual performance during high-intensity cycling. In highly trained cyclists, we found a strong activation of the RF during hip flexion. This results in reduced negative force in the fourth quadrant of the pedal cycle. Furthermore, we discovered that pre-activation of the RF during hip flexion reduces force loss at the top dead center (TDC) and can improve force development during subsequent leg extension. Finally, we found that a higher performance level is associated with earlier and more intense coactivation of the RF and VL. This quadriceps femoris recruitment pattern improves force transmission and maintains propulsion at the TDC of the pedal cycle. Our results demonstrate neuromuscular adaptations in cycling that can be utilized to optimize training interventions in sports and rehabilitation.

Abstract Background Eye tracking (ET) is a powerful methodology for studying attentional processes through quantification of eye movements. The precision, usability, and cost-effectiveness of ET render it a promising platform for developing biomarkers for use in clinical trials for autism spectrum disorder (ASD). Methods The Autism Biomarkers Consortium for Clinical Trials conducted a multisite, observational study of 6–11-year-old children with ASD (n = 280) and typical development (TD, n = 119). The ET battery included: Activity Monitoring, Social Interactive, Static Social Scenes, Biological Motion Preference, and Pupillary Light Reflex tasks. A priori, gaze to faces in Activity Monitoring, Social Interactive, and Static Social Scenes tasks were aggregated into an Oculomotor Index of Gaze to Human Faces (OMI) as the primary outcome measure. This work reports on fundamental biomarker properties (data acquisition rates, construct validity, six-week stability, group discrimination, and clinical relationships) derived from these assays that serve as a base for subsequent development of clinical trial biomarker applications. Results All tasks exhibited excellent acquisition rates, met expectations for construct validity, had moderate or high six-week stabilities, and highlighted subsets of the ASD group with distinct biomarker performance. Within ASD, higher OMI was associated with increased memory for faces, decreased autism symptom severity, and higher verbal IQ and pragmatic communication skills. Limitations No specific interventions were administered in this study, limiting information about how ET biomarkers track or predict outcomes in response to treatment. This study did not consider co-occurrence of psychiatric conditions nor specificity in comparison with non-ASD special populations, therefore limiting our understanding of the applicability of outcomes to specific clinical contexts-of-use. Research-grade protocols and equipment were used; further studies are needed to explore deployment in less standardized contexts. Conclusions All ET tasks met expectations regarding biomarker properties, with strongest performance for tasks associated with attention to human faces and weakest performance associated with biological motion preference. Based on these data, the OMI has been accepted to the FDA’s Biomarker Qualification program, providing a path for advancing efforts to develop biomarkers for use in clinical trials.

Glioblastoma (GBM) contains cancer stem cells (CSC) that are resistant to treatment. GBM CSC expresses glycolipids recognized by the A2B5 antibody. A2B5, induced by the enzyme ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyl transferase 3 (ST8Sia3), plays a crucial role in the proliferation, migration, clonogenicity and tumorigenesis of GBM CSC. Our aim was to characterize the resulting effects of neuraminidase that removes A2B5 in order to target GBM CSC. To this end, we set up a GBM organotypic slice model; quantified A2B5 expression by flow cytometry in U87-MG, U87-ST8Sia3 and GBM CSC lines, treated or not by neuraminidase; performed RNAseq and DNA methylation profiling; and analyzed the ganglioside expression by liquid chromatography–mass spectrometry in these cell lines, treated or not with neuraminidase. Results demonstrated that neuraminidase decreased A2B5 expression, tumor size and regrowth after surgical removal in the organotypic slice model but did not induce a distinct transcriptomic or epigenetic signature in GBM CSC lines. RNAseq analysis revealed that OLIG2, CHI3L1, TIMP3, TNFAIP2, and TNFAIP6 transcripts were significantly overexpressed in U87-ST8Sia3 compared to U87-MG. RT-qPCR confirmed these results and demonstrated that neuraminidase decreased gene expression in GBM CSC lines. Moreover, neuraminidase drastically reduced ganglioside expression in GBM CSC lines. Neuraminidase, by its pleiotropic action, is an attractive local treatment against GBM.

Abstract An estimation of the impact of climatic conditions—measured with an index that combines temperature and humidity, the IPTCC—on the hospitalizations and deaths attributed to SARS-CoV-2 is proposed. The present paper uses weekly data from 54 French administrative regions between March 23, 2020 and January 10, 2021. Firstly, a Granger causal analysis is developed and reveals that past values of the IPTCC contain information that allow for a better prediction of hospitalizations or deaths than that obtained without the IPTCC. Finally, a vector autoregressive model is estimated to evaluate the dynamic response of hospitalizations and deaths after an increase in the IPTCC. It is estimated that a 10-point increase in the IPTCC causes hospitalizations to rise by 2.9% (90% CI 0.7–5.0) one week after the increase, and by 4.1% (90% CI 2.1–6.4) and 4.4% (90% CI 2.5–6.3) in the two following weeks. Over ten weeks, the cumulative effect is estimated to reach 20.1%. Two weeks after the increase in the IPTCC, deaths are estimated to rise by 3.7% (90% CI 1.6–5.8). The cumulative effect from the second to the tenth weeks reaches 15.8%. The results are robust to the inclusion of air pollution indicators.

Abstract Background Identification of ASD biomarkers is a key priority for understanding etiology, facilitating early diagnosis, monitoring developmental trajectories, and targeting treatment efforts. Efforts have included exploration of resting state encephalography (EEG), which has a variety of relevant neurodevelopmental correlates and can be collected with minimal burden. However, EEG biomarkers may not be equally valid across the autism spectrum, as ASD is strikingly heterogeneous and individual differences may moderate EEG-behavior associations. Biological sex is a particularly important potential moderator, as females with ASD appear to differ from males with ASD in important ways that may influence biomarker accuracy. Methods We examined effects of biological sex, age, and ASD diagnosis on resting state EEG among a large, sex-balanced sample of youth with (N = 142, 43% female) and without (N = 138, 49% female) ASD collected across four research sites. Absolute power was extracted across five frequency bands and nine brain regions, and effects of sex, age, and diagnosis were analyzed using mixed-effects linear regression models. Exploratory partial correlations were computed to examine EEG-behavior associations in ASD, with emphasis on possible sex differences in associations. Results Decreased EEG power across multiple frequencies was associated with female sex and older age. Youth with ASD displayed decreased alpha power relative to peers without ASD, suggesting increased neural activation during rest. Associations between EEG and behavior varied by sex. Whereas power across various frequencies correlated with social skills, nonverbal IQ, and repetitive behavior for males with ASD, no such associations were observed for females with ASD. Conclusions Research using EEG as a possible ASD biomarker must consider individual differences among participants, as these features influence baseline EEG measures and moderate associations between EEG and important behavioral outcomes. Failure to consider factors such as biological sex in such research risks defining biomarkers that misrepresent females with ASD, hindering understanding of the neurobiology, development, and intervention response of this important population.

Introduction Patients who have external ventricular drainage (EVD) inserted are prone to many risks and complications. Intraventricular hemorrhage (IVH) is a frequent and life-threatening complication for spontaneous intracerebral hemorrhage (ICH) and results in an increased morbidity and mortality for those patients. An EVD insertion is a frequent surgical procedure for those with IVH. However, it is also known that IVH patients have a much higher rate of ventricular catheter occlusion. We hypothesize that blood clots have a predominant participation as a pathophysiological mechanism for EVD occlusion, and that a different and more appropriate catheter design might decrease the occlusion rate occurring during the utilization of EVDs on patients with IVH and, therefore, reduce implantation time. Methods The electronic data sheets of 30 patients with spontaneous IVH from March 2014 until April 2015 were evaluated. Two concepts in catheter design were evaluated: A group of 15 patients with a conventional type of catheter inserted was identified as Group C (conventional). A group of 15 patients with a new design of catheter inserted was identified as Group H (hemorrhagic). Both groups were compared regarding survival end parameters, outcomes, days spent in intensive care units (ICUs) and time spent with EVDs implanted. Results Hospitalization at the ICU was statistically significantly reduced for Group H compared with Group C. There was no significant difference among the hospitalization days between both groups. There was no statistical difference either for acute hydrocephalus or death rate. External ventricular drainage implantation days were significantly reduced for Group H related to Group C. Conclusion The results of the present study points to the fact that, although apparently the new catheter design did not change some secondary complications such as hydrocephalus and hospitalization rate, it seems that a better or specifically designed catheter for IVH purposes might lead to less ICU hospitalization days and EVD implantation days, two factors that have economic impact on healthcare due to the reduction of hospitalization costs and reduced incidence of related complications. The information obtained by this preliminary study should be grounded by a larger, more detailed and prospective evaluation; if these preliminary data are maintained, the new design should be considered for IVH associated EVDs insertions.

Abstract This work aims at developing and validating mathematical models and empirically evaluating a water‐film cooling system for commercial photovoltaic modules. Methodologically, thermal, electrical and climatological data measured in a specific purpose on‐grid outdoor test unit were used. In this work they are used to study the improvement in the performance of photovoltaic energy production due to temperature reduction. The first‐order state‐space linear parametric model presents the best performance to predict the temperature of the uncooled photovoltaic modules, with normalised mean square error (NRMSE) of 86.75%. In contrast, the non‐linear model performance of cooled photovoltaic modules is lower, with NRMSE of 44.5%; however, the results show that the performance of the complete thermoelectric model is satisfactory, with NRMSE of 76.38%. On the other hand, empirical tests showed that the cooling system reduces temperature in 15–19%, on average, and to a maximum of 35%. In terms of power, there are average gains of 5–9%, and maximum gains of 12%. Regarding gross generation, there are average gains of 2.3–6%, and maximum gains of 12%. It was concluded that it is possible to mathematically model and predict this generation using non‐linear models with a 0.2% error between modelled and measured generation.

Abstract Background Imputation accuracy among other things depends on the size of the reference panel, the marker’s minor allele frequency (MAF), and the correct placement of single nucleotide polymorphism (SNP) on the reference genome assembly. Using high-density genotypes of 3938 Nellore cattle from Brazil, we investigated the accuracy of imputation from 50 K to 777 K SNP density using Minimac3, when map positions were determined according to the bovine genome assemblies UMD3.1 and ARS-UCD1.2. We assessed the effect of reference and target panel sizes on the pre-phasing based imputation quality using ten-fold cross-validation. Further, we compared the reliability of the model-based imputation quality score (Rsq) from Minimac3 to the empirical imputation accuracy. Results The overall accuracy of imputation measured as the squared correlation between true and imputed allele dosages (R2 dose) was almost identical using either the UMD3.1 or ARS-UCD1.2 genome assembly. When the size of the reference panel increased from 250 to 2000, R2 dose increased from 0.845 to 0.917, and the number of polymorphic markers in the imputed data set increased from 586,701 to 618,660. Advantages in both accuracy and marker density were also observed when larger target panels were imputed, likely resulting from more accurate haplotype inference. Imputation accuracy increased from 0.903 to 0.913, and the marker density in the imputed data increased from 593,239 to 595,570 when haplotypes were inferred in 500 and 2900 target animals. The model-based imputation quality scores from Minimac3 (Rsq) were systematically higher than empirically estimated accuracies. However, both metrics were positively correlated and the correlation increased with the size of the reference panel and MAF of imputed variants. Conclusions Accurate imputation of BovineHD BeadChip markers is possible in Nellore cattle using the new bovine reference genome assembly ARS-UCD1.2. The use of large reference and target panels improves the accuracy of the imputed genotypes and provides genotypes for more markers segregating at low frequency for downstream genomic analyses. The model-based imputation quality score from Minimac3 (Rsq) can be used to detect poorly imputed variants but its reliability depends on the size of the reference panel and MAF of the imputed variants.

Background Neurological COVID-19 disease has been reported widely, but published studies often lack information on neurological outcomes and prognostic risk factors. We aimed to describe the spectrum of neurological disease in hospitalised COVID-19 patients; characterise clinical outcomes; and investigate factors associated with a poor outcome. Methods We conducted an individual patient data (IPD) meta-analysis of hospitalised patients with neurological COVID-19 disease, using standard case definitions. We invited authors of studies from the first pandemic wave, plus clinicians in the Global COVID-Neuro Network with unpublished data, to contribute. We analysed features associated with poor outcome (moderate to severe disability or death, 3 to 6 on the modified Rankin Scale) using multivariable models. Results We included 83 studies (31 unpublished) providing IPD for 1979 patients with COVID-19 and acute new-onset neurological disease. Encephalopathy (978 [49%] patients) and cerebrovascular events (506 [26%]) were the most common diagnoses. Respiratory and systemic symptoms preceded neurological features in 93% of patients; one third developed neurological disease after hospital admission. A poor outcome was more common in patients with cerebrovascular events (76% [95% CI 67–82]), than encephalopathy (54% [42–65]). Intensive care use was high (38% [35–41]) overall, and also greater in the cerebrovascular patients. In the cerebrovascular, but not encephalopathic patients, risk factors for poor outcome included breathlessness on admission and elevated D-dimer. Overall, 30-day mortality was 30% [27–32]. The hazard of death was comparatively lower for patients in the WHO European region. Interpretation Neurological COVID-19 disease poses a considerable burden in terms of disease outcomes and use of hospital resources from prolonged intensive care and inpatient admission; preliminary data suggest these may differ according to WHO regions and country income levels. The different risk factors for encephalopathy and stroke suggest different disease mechanisms which may be amenable to intervention, especially in those who develop neurological symptoms after hospital admission.