Observation of Seven Astrophysical Tau Neutrino Candidates with IceCube.

We report on a measurement of astrophysical tau neutrinos with 9.7 yr of IceCube data. Using convolutional neural networks trained on images derived from simulated events, seven candidate ν_{τ} events were found with visible energies ranging from roughly 20 TeV to 1 PeV and a median expected parent ν_{τ} energy of about 200 TeV. Considering backgrounds from astrophysical and atmospheric neutrinos, and muons from π^{±}/K^{±} decays in atmospheric air showers, we obtain a total estimated background of about 0.5 events, dominated by non-ν_{τ} astrophysical neutrinos. Thus, we rule out the absence of astrophysical ν_{τ} at the 5σ level. The measured astrophysical ν_{τ} flux is consistent with expectations based on previously published IceCube astrophysical neutrino flux measurements and neutrino oscillations.

[French practical guidelines for the diagnosis and management of IPF - 2021 update, full version]. / Recommandations pratiques pour le diagnostic et la prise en charge de la fibrose pulmonaire idiopathique ­ Actualisation 2021. Version intégrale.

BACKGROUND: Since the previous French guidelines were published in 2017, substantial additional knowledge about idiopathic pulmonary fibrosis has accumulated. METHODS: Under the auspices of the French-speaking Learned Society of Pulmonology and at the initiative of the coordinating reference center, practical guidelines for treatment of rare pulmonary diseases have been established. They were elaborated by groups of writers, reviewers and coordinators with the help of the OrphaLung network, as well as pulmonologists with varying practice modalities, radiologists, pathologists, a general practitioner, a head nurse, and a patients' association. The method was developed according to rules entitled "Good clinical practice" in the overall framework of the "Guidelines for clinical practice" of the official French health authority (HAS), taking into account the results of an online vote using a Likert scale. RESULTS: After analysis of the literature, 54 recommendations were formulated, improved, and validated by the working groups. The recommendations covered a wide-ranging aspects of the disease and its treatment: epidemiology, diagnostic modalities, quality criteria and interpretation of chest CT, indication and modalities of lung biopsy, etiologic workup, approach to familial disease entailing indications and modalities of genetic testing, evaluation of possible functional impairments and prognosis, indications for and use of antifibrotic therapy, lung transplantation, symptom management, comorbidities and complications, treatment of chronic respiratory failure, diagnosis and management of acute exacerbations of fibrosis. CONCLUSION: These evidence-based guidelines are aimed at guiding the diagnosis and the management in clinical practice of idiopathic pulmonary fibrosis.

[French practical guidelines for the diagnosis and management of IPF - 2021 update, short version]. / Recommandations pratiques pour le diagnostic et la prise en charge de la fibrose pulmonaire idiopathique ­ Actualisation 2021. Version courte.

BACKGROUND: Since the previous French guidelines were published in 2017, substantial additional knowledge about idiopathic pulmonary fibrosis has accumulated. METHODS: Under the auspices of the French-speaking Learned Society of Pulmonology and at the initiative of the coordinating reference center, practical guidelines for treatment of rare pulmonary diseases have been established. They were elaborated by groups of writers, reviewers and coordinators with the help of the OrphaLung network, as well as pulmonologists with varying practice modalities, radiologists, pathologists, a general practitioner, a head nurse, and a patients' association. The method was developed according to rules entitled "Good clinical practice" in the overall framework of the "Guidelines for clinical practice" of the official French health authority (HAS), taking into account the results of an online vote using a Likert scale. RESULTS: After analysis of the literature, 54 recommendations were formulated, improved, and validated by the working groups. The recommendations covered a wide-ranging aspects of the disease and its treatment: epidemiology, diagnostic modalities, quality criteria and interpretation of chest CT, indication and modalities of lung biopsy, etiologic workup, approach to familial disease entailing indications and modalities of genetic testing, evaluation of possible functional impairments and prognosis, indications for and use of antifibrotic therapy, lung transplantation, symptom management, comorbidities and complications, treatment of chronic respiratory failure, diagnosis and management of acute exacerbations of fibrosis. CONCLUSION: These evidence-based guidelines are aimed at guiding the diagnosis and the management in clinical practice of idiopathic pulmonary fibrosis.

Lipid excess affects chaperone-mediated autophagy in hypothalamus.

Obesity is a major health problem worldwide. Overweight and obesity directly affect health-related quality of life and also have an important economic impact on healthcare systems. In experimental models, obesity leads to hypothalamic inflammation and loss of metabolic homeostasis. It is known that macroautophagy is decreased in the hypothalamus of obese mice but the role of chaperone-mediated autophagy is still unknown. In this study, we aimed to investigate the role of hypothalamic chaperone-mediated autophagy in response to high-fat diet and also the direct effect of palmitate on hypothalamic neurons. Mice received chow or high-fat diet for 3 days or 1 week. At the end of the experimental protocol, chaperone-mediated autophagy in hypothalamus was investigated, as well as cytokines expression. In other set of experiments, neuronal cell lines were treated with palmitic acid, a saturated fatty acid. We show that chaperone-mediated autophagy is differently regulated in response to high-fat diet intake for 3 days or 1 week. Also, when hypothalamic neurons are directly exposed to palmitate there is activation of chaperone-mediated autophagy. High-fat diet causes hypothalamic inflammation concomitantly to changes in the content of chaperone-mediated autophagy machinery. It remains to be studied the direct role of inflammation and lipids itself on the activation of chaperone-mediated autophagy in the hypothalamus in vivo and also the neuronal implications of chaperone-mediated autophagy inhibition in response to obesity.

Previous in-home physiotherapy prevents institutionalization after short-term hospitalization in community-dwelling older dependent people.

AIMS: Short-term hospitalization of community-dwelling older dependent people in a geriatric acute care unit is sometimes needed to treat an acute health problem. Serious loss of independence can lead to difficulties in maintaining home care and is followed, at hospital discharge, to institutionalization in a long-term care home. We investigated the variables, particularly those related to the paramedical staff at home, predicting a return home or an institutionalization at hospital discharge. METHODS: Retrospective observational study of 398 sixty and more year-old patients, living at home, having a natural caregiver, and hospitalized in an acute care unit of the State Geriatric Center. RESULTS: 289 (72.6%) patients returned home, 101 (25.3%) were admitted in a long-term care home, and 8 (2%) died. Independent predictors of institutionalization were length of stay in the acute care unit [adjusted OR (AOR) = 1.102, P < 0.001], disruptive behavioral and psychological symptoms of dementia (BPSD, AOR = 1.827, P = 0.039), caregiver burden (AOR = 1.976, P = 0.038), moderately severe-to-severe cognitive impairment (AOR = 2.121, P = 0.011), and living alone with a close or a remote caregiver (AOR = 2.620 and 4.446, P = 0.003 and 0.001, respectively). In-home physiotherapy was independently associated (AOR = 0.393, P = 0.002) with a lower risk of institutionalization. CONCLUSION: In-home physiotherapy should be recommended to community-dwelling older dependent people, especially if they are living alone and/or if they present disruptive BPSD and/or moderately severe-to-severe cognitive impairment.

Motor-cortex excitability and response variability following paired-associative stimulation: a proof-of-concept study comparing individualized and fixed inter-stimulus intervals.

While diverging efficacy and inter-individual response variability have repeatedly been reported for paired-associative stimulation (PAS), approaches to overcome these issues are yet lacking. Hence, the aim of the present study was to determine whether response variability could be reduced through the application of an individualized PAS paradigm. Changes of transcranial magnetic stimulation (TMS) elicited motor-evoked potentials (MEP) following different PAS paradigms were assessed in three experimental conditions. According to a within-subjects design, 21 participants received three consecutive PAS paradigms differing with respect to the applied inter-stimulus intervals (ISI) between peripheral nerve stimulation (PNS) and TMS. Based on foregoing considerations, we compared fixed ISI of 25 ms (PAS 25) and 22 ms (PAS 22) to an individualized PAS paradigm accounting for conduction time differences on the single subject level (iPAS). Overall, we did not observe significantly increased post-stimulation MEP magnitudes in any of the three experimental paradigms. Explorative analyses revealed increased inter-individual response variability in case of PAS 25 and PAS 22 compared to higher rates of expected MEP magnitude increases in case of our iPAS paradigm. The findings of our proof-of-concept study points towards a potential association of decreased inter-individual variability with individually selected ISI that account for differences in conduction time. However, as our findings did not reach the significance threshold, our study highlights the issue of intra-individual variability in PAS paradigms. Further replication studies with larger sample sizes and repetitive designs are needed to confirm our findings.

[Hypersensitivity pneumonitis and abscess reaction to nontuberculous mycobacteria acquired form jacuzzi aerosol]. / Pneumopathie d'hypersensibilité à mycobactéries atypiques se compliquant d'un abcès à Mycobacterium intracellulare.

INTRODUCTION: Mycobacterium avium complex can be responsible for a number of different radio-clinical presentations, ranging from invasive infections to hypersensitivity pneumonitis due to repeated inhalation of antigens. The diagnosis of hypersensitivity pneumonitis is clinical, radiological, biological and microbiological. CASE REPORT: A 61-year-old male developed a hypersensitivity pneumonitis reaction to non-tuberculous mycobacteria, following the repeated use of his own spa, which later evolved into chronic respiratory failure. The diagnosis was made via an environmental analysis. Immunosuppressive treatment comprising corticosteroids and methotrexate led to moderate improvement, but may also have been responsible for the development of a M. intracellulare abscess. Despite 12 months of well-conducted antibiotic treatment, the evolution was unfavourable, with a relapse of a M. intracellulare infection three months after the end of treatment, followed by the patient's death. CONCLUSION: Hypersensitivity pneumonitis reaction to non-tuberculous mycobacteria should be considered in patients who have their own spa. In the absence of microbiological identification, environmental analysis may guide the diagnosis. A fatal evolution of PHS is infrequent but prognosis may depend on the degree of associated fibrosis.

Genetic testing among Spanish pediatric neurologists: Knowledge, attitudes and practices.

Advances in genetic testing applied to child neurology have enabled the development of genetic tests with greater sensitivity in elucidating an etiologic diagnosis for common neurological conditions. The objective of the current study was to examine child neurologists' perspectives and insights into genetic testing. We surveyed 118 Spanish child neurologists, exploring their knowledge, attitudes, and practices concerning genetic tests. All of them had requested at least one genetic test in the past six months. Global developmental delay or intellectual disability in absence of a strong specific etiologic suspicion and autism spectrum disorders were the disorders for which genetic testing was most frequently requested. The most commonly requested genetic test was CGH-array. Overall, child neurologist perception of readiness for making genetic-related decisions was not bad, although many would like to have a greater support from geneticists and were interested in increasing the time dedicated to genetics within their continuing education program. These data have important implications for future practice, research, and education.

Anatomic feasibility of a new endopelvic approach for iliac crest bone harvesting.

PURPOSE: For the past few years, anterior exposure for surgery of the lumbar spine has gained popularity for the treatment of disk disease or spondylosis. Cancellous bone remains the gold standard for fusion. Iliac crest bone harvesting is safe but there are donor site complications. Bone substitutes exist, like recombinant human bone morphogenic protein-2 rhBMP-2. This alternative offers a high rate of fusion but with local and general complications. The aim of our study is to show the feasibility of an endopelvic approach for iliac bone crest harvesting to avoid donor site complication. METHOD: Twenty anterior retroperitoneal lumbar spine approaches have been realized in the anatomy department of the University of Bordeaux. The volumes of cancellous bone have been measured and procedure complications have been reported. RESULTS: The mean volume of cancellous bone was 5.9 cc, the maximum volume was 8.2 cc and the minimum volume was 4.5 cc. No complications have been reported during the approach or the bone harvesting. CONCLUSIONS: Anterior retroperitoneal approach for iliac bone crest harvesting is a safe way to obtain sufficient volume of cancellous bone for a single lumbar spinal fusion. This exposure avoids the risks of an iliac crest donor site complications or rhBMP-2 complications.

Adsorption of Bovine Serum Albumin (BSA) at the Oil/Water Interface: A Neutron Reflection Study.

The structure of the adsorbed protein layer at the oil/water interface is essential to the understanding of the role of proteins in emulsion stabilization, and it is important to glean the mechanistic events of protein adsorption at such buried interfaces. This article reports on a novel experimental methodology for probing protein adsorption at the buried oil/water interface. Neutron reflectivity was used with a carefully selected set of isotopic contrasts to study the adsorption of bovine serum albumin (BSA) at the hexadecane/water interface, and the results were compared to those for the air/water interface. The adsorption isotherm was determined at the isoelectric point, and the results showed that a higher degree of adsorption could be achieved at the more hydrophobic interface. The adsorbed BSA molecules formed a monolayer on the aqueous side of the interface. The molecules in this layer were partially denatured by the presence of oil, and once released from the spatial constraint by the globular framework they were free to establish more favorable interactions with the hydrophobic medium. Thus, a loose layer extending toward the oil phase was clearly observed, resulting in an overall broader interface. By analogy to the air/water interface, as the concentration of BSA increased to 1.0 mg mL(-1) a secondary layer extending toward the aqueous phase was observed, possibly resulting from the steric repulsion upon the saturation of the primary monolayer. Results clearly indicate a more compact arrangement of molecules at the oil/water interface: this must be caused by the loss of the globular structure as a consequence of the denaturing action of the hexadecane.

[Outbreak of hand, foot and mouth disease with onychomadesis caused by Coxsackie virus A16 in Granada]. / Brote de enfermedad boca-mano-pie y onicomadesis causado por el virus Coxsackie A16, Granada.

INTRODUCTION: Due to the significant increase in the number of cases of hand, foot and mouth disease (HFMD) among pre-school children population during late 2011 and early 2012. A study has been proposed with the aim of describing the HFMD outbreak and analyzing the risk factors associated with suffering onychomadesis. PATIENTS AND METHODS: A descriptive and analytical case-control study was designed. The study population was 376 children between 6 and 36 months old, living in the Basic Health Catchment area of Peligros (Granada). The study inclued an epidemiological survey of 28 cases and paired controls in order to collect data on the time, person and place, and implementing preventive actions and family health education. Finally a microbiological viral study of stool samples was made. RESULTS: There were 64% of girls with average age 20.8 months. The clinical signs fornd were, fever (75%), vesicular palmar eruption (71%), plantar eruption (68%), erosive stomatitis (64%), and nail loss (46%). The risk of getting sick was 14 times greater for those children attending a childcare centre and had contact with sick cases (OR 13.8; 95% CI; 3.79-50.18). The average time since onset of symptoms and onychomadesis was 52 days, and its appearance was linked to the presence of ulcers in mouth (P=.006). Five samples were positive to enteroviruses Coxsackie A16. CONCLUSION: There was an outbreak of HFMD detected by pediatricians and families. The cases presented with marked clinical symptoms, and the nail loss (onychomadesis) generated a social alarm. The cause of the outbreak was an enterovirus Coxsackie A16 transmitted among sick cases and through childcare centres.

Diurnal behavior of dairy cows on alfalfa pastures supplemented with corn silage and concentrate / Comportamento diurno de vacas leiteiras em pastagem de alfafa suplementada com silagem de milho e concentrado

The diurnal ingestive behavior of dairy cows on alfalfa pastures supplemented with corn silage and concentrate was evaluated. Sixteen Holstein dairy cows in mid-lactation were used in a randomized block design. The treatments were partial replacement of corn silage for limited alfalfa grazing time (LGT) or unlimited grazing time (UGT). Rotational alfalfa grazing was used and the amount of concentrate fed was the same in both treatments. Behavioral activities observed were time spent grazing, rumination and idleness, during four days, from 8:00 AM to 7:00 PM. From 2:00 to 5:00 PM grazing was intermittent and short-lasting on UGT, whereas on LGT grazing activity was longer than UGT in the morning and at the end of the afternoon. Restriction in available grazing time clearly influenced the distribution of time spent with grazing, rumination and idleness throughout the day. However, this effect was not observed in the total time spent in these activities...

Avaliou-se o comportamento ingestivo de vacas leiteiras com acesso restrito ou irrestrito a uma pastagem de alfafa suplementada com silagem de milho e concentrado. Utilizaram-se 16 vacas da raça Holandesa, em estádio médio de lactação, em delineamento em blocos ao acaso. Os tratamentos foram: silagem de milho substituída parcialmente por pastejo restrito ou irrestrito de alfafa. As vacas foram manejadas em sistema de pastejo rotacionado e a quantidade de concentrado foi igual em ambos os tratamentos. As atividades comportamentais observadas foram pastejo, ruminação e ócio, das oito às 19 horas, em quatro ocasiões. No pastejo irrestrito, observou-se que, nos horários entre 14 e 17 horas, o pastejo foi intermitente e de curta duração, enquanto no pastejo restrito a atividade de pastejo foi mais prolongada durante a manhã e no final da tarde. A restrição no tempo disponível para pastejo da alfafa influenciou marcadamente a distribuição, no decorrer do dia, do tempo gasto em pastejo, da ruminação e do ócio. Entretanto, não se observou este efeito no tempo total gasto nestas atividades...

Histological and ultra-structural effects of rapid muscle expansion through intramuscular administration of carbon dioxide: an intra-operative study in an animal model.

INTRODUCTION: Carbon dioxide (CO2) therapy refers to trans-cutaneous or sub-cutaneous administration of CO2 for therapeutic purposes, and recent studies have pointed out that it produces a vasodilation effect after it is locally injected, which helps amplify the reconstructive potentiality of an expanded-muscle flap. MATERIALS AND METHODS: Thirty male Wistar rats, weighting between 350 and 400 g, were randomly divided into three groups of 10. In the first group, single intra-operative rapid expansion was carried out under the right latissimus dorsi muscle. In the second group, for five days prior to surgery, a pre-treatment with intramuscular injections of CO2 was performed. The third group served as controls. For each group, the latissimus dorsi muscle was fixed as soon possible after mice died, and ultrathin sections of it examined with transmission electron microscope. RESULTS: In the treated group, the majority of expanded muscles showed a normal striation pattern, whereas a few fibers showed mild disorganization of the myo-filaments in the sarcomeres, which appeared overstretched (average 2.37 µm). CONCLUSIONS: This evidence could demonstrate a greater capacity of muscle recovery after treatment by CO2 expansion.

Hepatic enzymes activity in the fish Prochilodus lineatus (Valenciennes, 1836) after sublethal cypermethrin exposure.

Prochilodus lineatus, a fish, was exposed to sublethal concentrations of cypermethrin: 0.075, 0.150, and 0.300 µg L(-1) and a control group (without cypermethrin) for 96 h. Five specimens were exposed in each concentration for triplicate (n = 60). Hepatic biochemical values and behavioral changes were studied. The results revealed a significantly higher level of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase in hepatic tissue at different concentrations of cypermethrin tested compared to control (p < 0.05). A decrease in total protein was observed in exposed groups but not significantly (p > 0.05). This study provides information to know toxic mechanisms of cypermethrin on hepatic enzymes of P. lineatus that are poorly understood.

Paternal origins of Chinese cattle.

To determine the genetic diversity and paternal origin of Chinese cattle, 302 males from 16 Chinese native cattle breeds as well as 30 Holstein males and four Burma males as controls were analysed using four Y-SNPs and two Y-STRs. In Chinese bulls, the taurine Y1 and Y2 haplogroups and indicine Y3 haplogroup were detected in seven, 172 and 123 individuals respectively, and these frequencies varied among the Chinese cattle breeds examined. Y2 dominates in northern China (91.4%), and Y3 dominates in southern China (90.8%). Central China is an admixture zone, although Y2 predominates overall (72.0%). The geographical distributions of the Y2 and Y3 haplogroup frequencies revealed a pattern of male indicine introgression from south to north China. The three Y haplogroups were further classified into one Y1 haplotype, five Y2 haplotypes and one Y3 haplotype in Chinese native bulls. Due to the interplay between taurine and indicine types, Chinese cattle represent an extensive reservoir of genetic diversity. The Y haplotype distribution of Chinese cattle exhibited a clear geographical structure, which is consistent with mtDNA, historical and geographical information.

Haematophagous bat bites in Ecuadorian Amazon: characterisation and implications for sylvatic rabies prevention.

OBJECTIVE: To characterise the risk factors of haematophagous bat bites and to provide information to contribute to the prevention of rabies in Ecuador. DESIGN: Cross-sectional study based on interviews with 3518 individuals, from which two sets of variables were generated: characteristics of haematophagous bat attacks in the previous year among humans and risk factors for being bitten. METHODS: Data were analysed using multivariate logistic regression models, taking history of bat bites in the previous year as the response variable. RESULTS: In the previous year 723 (20.6%, 95%CI 19.3-21.9) of the participants declared having received haematophagous bat bites and 50.4% in the previous month, giving an incidence rate of 10.4% (95%CI 9.6-11.6) per month. Sleeping on the floor or in a hammock (adjusted odds ratio [aOR] 1.58, 95%CI 1.21-2.06), not using a protective bed net (aOR 1.25, 95%CI 1.03-1.50) and living in a dwelling with permanent openings in the structure (aOR 1.49, 95%CI 1.12-1.95) were associated with a higher probability of bat bites. Those most affected were the group aged ≤12 years (age 13-19 years, aOR 0.39, 95%CI 0.32-0.48; age ≥20 years, aOR 0.67, 95%CI 0.50-0.90). CONCLUSION: Primary prevention based on pre-exposure vaccination would be justifiable given the high dispersion of the population and the high incidence of bat bites. As a secondary protective measure, communities should work towards increasing the use of protective measures and putting barriers in permanent openings in their dwellings.

Genetic programming as alternative for predicting development effort of individual software projects.

Statistical and genetic programming techniques have been used to predict the software development effort of large software projects. In this paper, a genetic programming model was used for predicting the effort required in individually developed projects. Accuracy obtained from a genetic programming model was compared against one generated from the application of a statistical regression model. A sample of 219 projects developed by 71 practitioners was used for generating the two models, whereas another sample of 130 projects developed by 38 practitioners was used for validating them. The models used two kinds of lines of code as well as programming language experience as independent variables. Accuracy results from the model obtained with genetic programming suggest that it could be used to predict the software development effort of individual projects when these projects have been developed in a disciplined manner within a development-controlled environment.

Characterization of cytochrome b diversity in Chinese domestic horses.

Previous mitochondrial DNA (mtDNA) D-loop and microsatellite studies have shown that Chinese horses have multiple maternal origins and high genetic diversity. To better characterize maternal genetic origins and diversity of Chinese domestic horses, we conducted a comprehensive analysis of 407 complete 1140 bp sequences of the horse mitochondrially encoded cytochrome b (CYTB) gene, including 323 horses from 13 Chinese indigenous breeds and 84 reference sequences from GenBank. A total of 114 haplotypes were identified, of which 73 appeared among the 13 Chinese horse breeds. The high mitochondrially encoded cytochrome b haplotypic diversity suggests multiple maternal origins in Chinese horses.