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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.

BackgroundNeurological 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.MethodsWe 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.ResultsWe 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.InterpretationNeurological 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.

The impact of endurance training on spinal neural circuitries remains largely unknown. Some studies have reported higher H-reflexes in endurance trained athletes and therefore, adaptations within the Ia afferent pathways after long term endurance training have been suggested. In the present study we tested the hypothesis that cyclists (n = 12) demonstrate higher Hoffmann reflexes (H-reflexes) compared to recreationally active controls (n = 10). Notwithstanding, highly significant differences in endurance performance (VO2peak: 60.6 for cyclists vs. 46.3 ml/min/kg for controls (p < 0.001) there was no difference in the size of the SOL H-reflex between cyclists and controls (Hmax/Mmax ratio 61.3 vs. 60.0%, respectively (p = 0.840). Further analyses of the H and M recruitment curves for SOL revealed a significant steeper slope of the M recruitment curve in the group of cyclists (76.2 ± 3.8° vs. 72.0 ± 4.4°, p = 0.046) without a difference in the H-recruitment curve (84.6 ± 3.0° vs. 85.0 ± 2.8°, p = 0.784) compared to the control group. Cycling is classified as an endurance sport and thus the findings of the present study do not further support the assumption that long-term aerobic training leads to a general increase of the H-reflex. Amongst methodological differences in assessing the H-reflex, the training-specific sensorimotor control of the endurance sport itself might differently affect the responsiveness of spinal motoneurons on Ia-afferent inputs.

Abstract: The objective of this work was to distinguish the sexual dimorphism of horses of the Campolina breed, by morphometric measurements, and to classify them according to sex, using discriminating functions. Two-hundred and fifteen horses were measured, and 39 morphometric measurements were evaluated. The analysis of covariance and the discriminant analysis were performed. Males were taller and showed a wider chest, a greater scapular-humeral angle, and a larger neck, both in length and circumference. Females had a larger heart girth, wider hips, and a greater opening of the coxal-ground and femorotibial angles. Regarding classification, circumference measurements (85.58%) were more accurate in sexual differentiation than the linear (83.26%) and angular (73.02%) ones. As to classification error, of the total animals measured, 10 to 20% of the females were categorized as males. In addition, 11 to 38% of the males were categorized as females. It can be concluded that of the 39 morphometric measurements evaluated, 22 are responsible for sexual dimorphism in the Campolina horse breed. Circumference and linear measurements provide a more assertive classification to determine sexual dimorphism. Angular measurements show greater classification errors regarding the gender of the horses.

Arteriovenous malformations (AVMs) of the brain are abnormal connections between the arterial and venous cerebral vasculature that often lead to intracranial hemorrhage (ICH). The diagnosis of AVMs often takes place in the setting of ICH, however, there is no clear consensus on how to manage critically ill, comatose patients and whether it is best to treat the lesion initially. We present an initial treatment strategy that is focused on the management of intracranial hypertension by the means of decompressive craniectomy (DC) coupled with delayed AVM management. We retrospectively reviewed the medical records of three patients who arrived with ICH, obliterated cisterns, and midline shifts greater than 5mm from ruptured AVMs. Each of these patients received a DC, with later definite treatment for their AVMs and cranioplasties. We reported the preoperative and postoperative clinical status of patients using Glasgow Coma Scale (GCS) outcomes as well as physical exam findings. All three patients were transferred to the intensive care immediately after DC and had significant clinical improvement 15 days post-craniectomy. All patients underwent definitive AVM treatment within 6 weeks of the initial procedure. One patient was treated with endovascular-only embolization while the other two received surgical treatment. Patients showed a significant improvement in neurological status and clinical outcome. Decompressive hemicraniectomies may have a positive impact on mortality and neurological outcomes for select patients with cerebral hemorrhage originating from vascular malformations, especially in low-resource scenarios.

In diesem Beitrag werden Daten von Primarschulkindern aus dem Kanton Zürich diskutiert. Individuelle Lernvoraussetzungen wurden via kognitive, sprachbezogene und affektive Variablen gemessen, ausserdem wurden die Sprachkompetenzen in Deutsch und Englisch über knapp zwei Schuljahre hinweg gemessen. Im Beitrag vergleiche ich verschiedene sonderpädagogisch geförderte Gruppen miteinander, sowohl im quer- als auch im Längsschnitt. Im Zentrum steht die Frage, ob gewisse Lernergruppen durch Fremdsprachen überfordert sind. Im Vergleich der Gruppen zeigt sich insbesondere im Längsschnitt, dass die sonderpädagogisch Geförderten im Vergleich zu den Nichtgeförderten nicht zurückfallen.

Endurance sports pose a plethora of mental demands that exercisers have to deal with. Unfortunately, investigations of exercise-specific demands and strategies to deal with them are insufficiently researched, leading to a gap in knowledge about athletic requirements and strategies used to deal with them. Here, we investigated which obstacles exercisers experience during an anaerobic (Wingate test) and an aerobic cycling test (incremental exercise test), as well as the strategies they considered helpful for dealing with these obstacles (qualitative analysis). In addition, we examined whether thinking of these obstacles and strategies in terms of if-then plans (or implementation intentions; i.e., “If I encounter obstacle O, then I will apply strategy S!”) improves performance over merely setting performance goals (i.e., goal intentions; quantitative analysis). N = 59 participants (age: M = 23.9 ± 6.5 years) performed both tests twice in a 2-within (Experimental session: 1 vs. 2) × 2-between (Condition: goal vs. implementation intention) design. Exercisers’ obstacles and strategies were assessed using structured interviews in Session 1 and subjected to thematic analysis. In both tests, feelings of exertion were the most frequently stated obstacle. Motivation to do well, self-encouragement, and focus on the body and on cycling were frequently stated strategies in both tests. There were also test-specific obstacles, such as boredom reported in the aerobic test. For session 2, the obstacles and strategies elicited in Session 1 were used to specify if-then plans. Bayesian mixed-factor ANOVA suggests, however, that if-then plans did not help exercisers to improve their performance. These findings shed novel light into the mental processes accompanying endurance exercise and the limits they pose on performance.

Endurance sports pose a plethora of mental demands that exercisers have to deal with. Unfortunately, investigations of exercise-specific demands and strategies to deal with them are insufficiently researched, leading to a gap in knowledge about athletic requirements and strategies used to deal with them. Here, we investigated which obstacles exercisers experience during an anaerobic (Wingate test) and an aerobic cycling test (incremental exercise test), as well as the strategies they considered helpful for dealing with these obstacles (qualitative analysis). In addition, we examined whether thinking of these obstacles and strategies in terms of if-then plans (or implementation intentions; i.e., "If I encounter obstacle O, then I will apply strategy S!") improves performance over merely setting performance goals (i.e., goal intentions; quantitative analysis). N = 59 participants (age: M = 23.9 ± 6.5 years) performed both tests twice in a 2-within (Experimental session: 1 vs. 2) × 2-between (Condition: goal vs. implementation intention) design. Exercisers' obstacles and strategies were assessed using structured interviews in Session 1 and subjected to thematic analysis. In both tests, feelings of exertion were the most frequently stated obstacle. Motivation to do well, self-encouragement, and focus on the body and on cycling were frequently stated strategies in both tests. There were also test-specific obstacles, such as boredom reported in the aerobic test. For session 2, the obstacles and strategies elicited in Session 1 were used to specify if-then plans. Bayesian mixed-factor ANOVA suggests, however, that if-then plans did not help exercisers to improve their performance. These findings shed novel light into the mental processes accompanying endurance exercise and the limits they pose on performance.

Previous research demonstrated that six sessions of cycling sprint-interval training (SIT) within a duration of only 2 weeks can increase endurance performance considerably. Primarily muscular mechanisms have been under investigation explaining such performance improvements. However, it has been shown in other exercise tasks that training-induced changes also occur at the level of the central nervous system. Therefore, we hypothesized to observe an enhanced neuromuscular performance in conjunction with an increase in endurance performance after 2 weeks of SIT. Therefore, we randomly assigned 19 healthy men (26 ± 5 years) to a control (n = 10) or a training group (n = 9), the latter performing a replication of the SIT protocol from Burgomaster et al. Before and after the training intervention, both groups performed a cycling endurance test until exhaustion. Neuromuscular function of the right vastus lateralis muscle was assessed before and after each endurance task by the means of maximal voluntary isometric contractions (MVCs). The variables of interest being MVC, voluntary activation was measured by peripheral nerve stimulations (VAPNS), by transcranial magnetic stimulation (VATMS), as well as potentiated resting twitches (Qtw,pot). We did not find any significant differences between the groups in the control variable time to exhaustion in the endurance task. In addition, we did not observe any time × group interaction effect in any of the neuromuscular parameters. However, we found a significant large-sized time effect in all neuromuscular variables (MVC, ηp2 = 0.181; VATMS, ηp2 = 0.250; VAPNS, ηp2 = 0.250; Qtw,pot, ηp2 = 0.304) as well as time to exhaustion ηp2 = 0.601). In contrast to other studies, we could not show that a short-term SIT is able to increase endurance performance. An unchanged endurance performance after training most likely explains the lack of differences in neuromuscular variables between groups. These findings demonstrate that replication studies are needed to verify results no matter how strong they seem to be. Differences over time for the variables of neuromuscular fatigue irrespective of group (MVC, + 9.3%; VATMS, + 0.2%; VAPNS, + 6.3%; Qtw,pot, + 6.3%) demonstrate test-retest effects that should be taken into consideration in future training studies and emphasize the inevitable necessity for controlled experiments.

In this contribution, I describe the evolution of the role that Alemannic dialects and Standard High German play in the Swiss German educational context. Drawing on a content analysis of a collection of school-related documents from 1950 to 2014, I describe the change in the roles attributed to dialects and the standard language, respectively. The task of German-language education shifts from the two-fold goal of teaching standard-language literacy and cultivating the “pure” dialect in the 1950s to a clear prioritization of standard language skills both in orality and in literacy towards the end of the twentieth century. I discuss these changes in relation to the backdrop of the media discourse on identity, language, multilingual education, language norms, and other social issues such as migration.

The position and number of hair whorls have been associated with the behavior, temperament, and laterality of horses. The easy observation of whorls assists in the prediction of reactivity, and thus permits the development of better measures of handling, training, mounting, and riding horses. However, little is known about the genetics involved in the formation of hair whorls. Therefore, the aim of this study was to perform a genome-wide association analysis to identify chromosome regions and candidate genes associated with hair whorl traits. Data from 342 Quarter Horses genotyped for approximately 53,000 SNPs were used in an association study using a single-step procedure. The following traits were analyzed: vertical position of hair whorl on the head, number of whorls on the head, and number of whorls on the left and right sides of the neck. The traits had between one and three genomic windows associated. Each of them explained at least 4% of the additive variance. The windows accounted for 20–80% of additive variance for each trait analyzed. Many of the prospected genes are related to hair follicle growth. Some of these genes exert a pleiotropic effect on neurological and behavioral traits. This is the first indication of biological and physiological activity that might explain the association of hair whorls and temperament.

Cattle are monotocous species and cow usually deliver one calf per birth. The present report has the aim to notify the birth occurrence of quadruplets of a Nelore cow: first time in scientific literature for this breed. The report presents negative and positive consequences of event.

Some language-acquisition researchers not only pursue their scholarly agenda but also act outside academia as experts in language policy-making. However, the relationship between scholarly quality and political impact is complicated, and oftentimes policy is not based on robust scholarly evidence. In this contribution, I focus on research findings in language learning that have been taken up in language planning and policy (e.g., the notion of linguistic interdependence). Drawing on concrete cases, I discuss problems of individual expertise and quality of research. Where there are methodological inadequacies and/or lack of expertise, problematic or even utterly false conclusions can be drawn from research. A critical review of influential claims in the field of applied linguistics with respect to robustness of the evidence and its fit to the actual policy problem should allow us to determine which theories and research strands may be useful for language-policy recommendations and which are probably not. A critical review of linguists’ involvement in policy-making suggests that often a more appropriate appellation for so-called evidence-based policy would be policy-based evidence. In my discussion, I address two delimitation problems: defining the boundary between pseudoscience and real science (in the wide sense of the term, including social sciences and humanities) and defining the boundary between scholarly rigor and political advocacy by academics.

Starting in the mid 1970s, Chile implemented comprehensive structural market reforms. Using manufacturing plant-level data on Chilean firms for years 1980 to 2001, we estimate the role of reforms on efficiency. We analyze aggregate productivity constructed from micro data to find that in the aftermath of the reforms, efficiency gains were explained by within-plant improvements and by the net entry of new units. We also find that plants producing traded goods and plants facing liquidity constraints experienced the largest efficiency gains. Trade openness and a superior access to external finance seem to have partially accounted for the improvement in manufacturing performance.

PURPOSE:Active recovery is often used by athletes after strenuous exercise or competition but its underlying mechanisms are not well understood. We hypothesized that active recovery speeds-up recovery processes within the muscle and the central nervous system (CNS). METHODS:We assessed muscular and CNS recovery by measuring the voluntary activation (VA) in the vastus lateralis muscle with transcranial magnetic stimulation (VATMS) and peripheral nerve stimulation (VAPNS) during maximal voluntary contractions (MVC) of the knee extensors in 11 subjects. Measurements were performed before and after a fatiguing cycling time-trial, after an active and a passive recovery treatment and after another fatiguing task (1 min MVC). The measurements were performed a second time 24 h after the time-trial. RESULTS:We observed a time × group interaction effect for VATMS (p = 0.013). Post-hoc corrected T-tests demonstrated an increased VATMS after active recovery when measured after the 1 min MVC performed 24 h after the time-trial (mean ± SD; 95.2 ± 4.1% vs. 89.2 ± 6.6%, p = 0.026). No significant effects were observed for all other variables. CONCLUSIONS:Active recovery increased aspects of central, rather than muscle recovery. However, no effect on MVC was seen, implying that even if active recovery speeds up CNS recovery, without affecting the recovery of muscle contractile properties, this doesn´t translate into increases in overall performance.

Stayability, which can be defined as the probability of a cow calving at a certain age when given the opportunity, is an important reproductive trait in beef cattle because it is directly related to herd profitability. The objective of this study was to estimate genetic parameters and to identify possible genomic regions associated with the phenotypic expression of stayability in Nellore cows. The variance components were estimated by Bayesian inference using a threshold animal model that included the systematic effects of contemporary group and sexual precocity and the random effects of animal and residual. The SNP effects were estimated by the single-step genomic BLUP method using information of 2,838 animals (2,020 females and 930 sires) genotyped with the Illumina High-Density BeadChip Array (San Diego, CA, USA). The variance explained by windows formed by 200 consecutive SNPs was used to identify genomic regions of largest effect on the expression of stayability. The heritability was 0.11 ± 0.01 when A matrix (pedigree) was used and 0.14 ± 0.01 when H matrix (relationship matrix that combines pedigree information and SNP data) was used. A total of 147 candidate genes for stayability were identified on chromosomes 1, 2, 5, 6, 9 and 20 and on the X chromosome. New candidate regions for stayability were detected, most of them related to reproductive, immunological and central nervous system functions.

A2B5+ cells isolated from human glioblastomas exhibit cancer stem cell properties. The A2B5 epitope belongs to the sialoganglioside family and is synthetized by the ST8 alpha-N-acetyl-neuraminidase α-2,8-sialyltransferase 3 (ST8SIA3) enzyme. Glycolipids represent attractive targets for solid tumors; therefore, the aim of this study was to decipher A2B5 function in glioblastomas. To this end, we developed cell lines expressing various levels of A2B5 either by genetically manipulating ST8SIA3 or by using neuraminidase. The overexpression of ST8SIA3 in low-A2B5-expressing cells resulted in a dramatic increase of A2B5 immunoreactivity. ST8SIA3 overexpression increased cell proliferation, migration, and clonogenicity in vitro and tumor growth when cells were intracranially grafted. Conversely, lentiviral ST8SIA3 inactivation in low-A2B5-expressing cells resulted in reduced proliferation, migration, and clonogenicity in vitro and extended mouse survival. Furthermore, in the shST8SIA3 cells, we found an active apoptotic phenotype. In high-A2B5-expressing cancer stem cells, lentiviral delivery of shST8SIA3 stopped cell growth. Neuraminidase treatment, which modifies the A2B5 epitope, impaired cell survival, proliferation, self-renewal, and migration. Our findings prove the crucial role of the A2B5 epitope in the promotion of proliferation, migration, clonogenicity, and tumorigenesis, pointing at A2B5 as an attractive therapeutic target for glioblastomas.

Bcl-2 is commonly overexpressed in tumors, where it is often associated with unfavorable outcome. However, it has also been linked to a favorable sensitivity to microtubule-targeting agents (MTAs). We show that Bcl-2– overexpressing lung and breast cancer cells were more sensitive to both paclitaxel and vinorelbine. Bcl-2 overexpression also significantly potentiated in vivo efficacy of paclitaxel, in terms of tumor volume decrease and survival benefits, in models of nude mice bearing lung cancer xenografts. To further investigate this favorable effect of Bcl-2, a genomic approach was taken. It revealed that Bcl-2 overexpression induced up-regulation of the proapoptotic protein Bim in lung cancer cells and that, conversely, Bcl-2 silencing decreased Bim expression level. A gene regulation study implicated the transcription factor Forkhead box-containing protein, class O3a in Bim up-regulation. Lastly, we show that Bim was responsible for MTA-triggered lung cancer cell death through a dynamin-related protein 1–mediated mitochondrial fragmentation. The Bcl-2–governed Bim induction evidence offers for the first time an explanation for the favorable higher sensitivity to treatment shown by Bcl-2–overexpressing cells. We suggest that Bim could be a powerful predictive factor for tumor response to MTA chemotherapy. Our data also give new insight into some failures in the efficacy of therapies targeted against Bcl-2.

Despite the potential of repetitive transcranial magnetic stimulation (rTMS) to improve performances in patients suffering from motor neuronal afflictions, its effect on motor performance enhancement in healthy subjects during a specific sport task is still unknown. We hypothesised that after an intermittent theta burst (iTBS) treatment, performance during the Wingate Anaerobic Test (WAnT), will increase and supraspinal fatigue following the exercise will be lower in comparison to a control treatment.Ten subjects participated in two randomised experiments consisting of a WAnT 5 minutes after either an iTBS or a control treatment. We determined voluntary activation (VA) of the right knee extensors with TMS (VATMS) and with peripheral nerve stimulation (VAPNS) of the femoral nerve, before and after the WAnT. T-tests were applied to the WAnT results and a 2 way within subject ANOVA was applied to VA results. The iTBS treatment increased the peak power and the maximum pedalling cadence and suppressed the reduction of VATMS following the WAnT compared to the control treatment. No behavioural changes related to fatigue (mean power and fatigue index) were observed.These results indicate for the first time that iTBS could be used as a potential intervention to improve anaerobic performance in a sport specific task.

The objective of this study was to perform a genome-wide association study (GWAS) to detect chromosome regions associated with indicator traits of sexual precocity in Nellore cattle. Data from Nellore animals belonging to farms which participate in the DeltaGen® and Paint® animal breeding programs, were used. The traits used in this study were the occurrence of early pregnancy (EP) and scrotal circumference (SC). Data from 72,675 females and 83,911 males with phenotypes were used; of these, 1,770 females and 1,680 males were genotyped. The SNP effects were estimated with a single-step procedure (WssGBLUP) and the observed phenotypes were used as dependent variables. All animals with available genotypes and phenotypes, in addition to those with only phenotypic information, were used. A single-trait animal model was applied to predict breeding values and the solutions of SNP effects were obtained from these breeding values. The results of GWAS are reported as the proportion of variance explained by windows with 150 adjacent SNPs. The 10 windows that explained the highest proportion of variance were identified. The results of this study indicate the polygenic nature of EP and SC, demonstrating that the indicator traits of sexual precocity studied here are probably controlled by many genes, including some of moderate effect. The 10 windows with large effects obtained for EP are located on chromosomes 5, 6, 7, 14, 18, 21 and 27, and together explained 7.91% of the total genetic variance. For SC, these windows are located on chromosomes 4, 8, 11, 13, 14, 19, 22 and 23, explaining 6.78% of total variance. GWAS permitted to identify chromosome regions associated with EP and SC. The identification of these regions contributes to a better understanding and evaluation of these traits, and permits to indicate candidate genes for future investigation of causal mutations.

Questo documento sulla valutazione è uno studio complementare alla Guida per lo sviluppo e l’attuazione di curricoli per una educazione plurilingue e interculturale del Consiglio d’Europa. Dà inizialmente una breve descrizione dei vari obiettivi della valutazione nell‘educazione plurilingue ed interculturale, cui segue una breve spiegazione di ciò che gli autori intendono con “valutazione“. Infine, descrive ed analizza la valutazione di alcune competenze correlate ad aspetti essenziali dell‘educazione plurilingue ed interculturale.ASSESSMENT IN PLURILINGUAL AND INTERCULTURAL EDUCATIONThis satellite to the Guide for the Development and Implementation of Curricula for Plurilingual and Intercultural Education focuses on assessment aspects. First, a brief overview is given of the various aims of assessment in plurilingual and intercultural education. The authors’ understanding of assessment is then briefly outlined. Finally, the assessment of selected competences having to do with core aspects of plurilingual and intercultural education is presented and discussed.

A partir de mediados de la década de los 70, Chile implementó un número relevante de reformas estructurales a sus mercados. En este trabajo estimamos el efecto de estas reformas sobre la eficiencia agregada, utilizando datos de plantas manufactureras chilenas para el período entre 1980 y 2001. Descomponemos la productividad agregada construida a partir de datos microeconómicos, encontrando que, luego de las reformas, las ganancias de eficiencia se explican tanto por mejoras al interior de las empresas como por la entrada neta de nuevos establecimientos. También encontramos que las mayores ganancias fueron obtenidas por las plantas que producen bienes transables y por aquellasrestringidas en su liquidez. Así, nuestros resultados sugieren que la apertura comercial y el mejor acceso al financiamiento externo explican en parte el mejor desempeño manufacturero en Chile.

Insulin growth factor I (IGF-I) and prolactin (PRL) are peptide hormones that exert complementary effects on reproductive traits by acting on folliculogenesis. In view of the lack of information about the IGF-I and PRL genes in Bos indicus, the objective of this study was to partially characterize the promoter regions of these genes and to screen animals of different ages at first pregnancy for the presence of polymorphisms in these regions. In addition, we determined whether polymorphisms influence the regulation of the two hormone genes, evaluating their association with sexual precocity. The animals were divided into three groups according to age at first pregnancy: 1) 100 heifers considered to be sexually precocious that became pregnant at 15-16 months of age, 2) 100 heifers that became pregnant during the normal breeding season at 24 months of age, and 3) 100 heifers that did not become pregnant until 24 months of age. For the IGF-I gene, PCR-RFLP-SnaBI analysis showed the presence of genotypes AB and BB at frequencies of 0.02 and 0.98, respectively. Sequencing of the IGF-I gene fragment revealed a single nitrogen base change from cytosine to thymine, corresponding to the restriction site of SnaBI. The polymorphisms identified in the 5’-flanking region of the IGF-I gene may serve as a basis for future studies of molecular markers in cattle. For the PRL gene, PCR-RFLP-HaeIII analysis showed the presence of only one migration pattern, a finding characterizing the region studied as monomorphic. The study of other regions in the IGF-I and PRL genes might provide molecular data that can be used in the future for the selection of sexually precocious animals.

Este artigo avalia o mercado reprimido de eletricidade, gás natural e álcool na Região Administrativa de Araçatuba (RAA), comparando o consumo com o consumo médio do estado de São Paulo e do estado da Flórida, EUA, onde se acredita que a demanda é plenamente satisfeita. O artigo apresenta uma projeção para o atendimento da demanda no contexto do desenvolvimento limpo em um cenário hipotético.This article assesses the restrained market of electricity, natural gas and alcohol in the Araçatuba Administrative Region (RAA), comparing the its consumption with the average consumption of the states of São Paulo and Florida (USA), where the demand is believed to be fully satisfied. Projections are made for answering the demand in a clean development context for a hypothetical scenario.

Cell-based assays (CBA) have increased the sensitivity of the neuromyelitis optica (NMO)-IgG/aquaporin-4-antibody detection compared to classical tissue-based indirect assays. We describe the sensitivity of an optimized immunohistochemistry (IHC-o) to detect NMO-IgG/aquaporin-4-antibody in comparison with that of two CBA: an in-house (CBA-ih) and a commercial (CBA-c) assay (Euroimmun, Germany). Coded serum from 103 patients with definite NMO and 122 inflammatory controls were studied by IHC-o, CBA-ih, and CBA-c. IHC-o used the same protocol described to detect antibodies against cell surface antigens. CBA-ih used live cells transfected with the aquaporin-4-M23-isoform. The sensitivity of the IHC-o was 74.8% (95% confidence interval [CI] 65-83) and was similar to that of the CBA-ih 75.7% (95% CI 66-84) and the CBA-c 73.8% (95% CI 64-82). The specificity of the three assays was 100% (95% CI 97-100). Interassay concordance was high, 100 of 103 samples were coincident in all techniques. The optimized immunohistochemistry proves to be as sensitive and specific as the cell-based assays. This assay extends the available tools for NMO-IgG/aquaporin-4-antibody detection.