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Background Antiretroviral therapy (ART) is crucial for controlling HIV-1 infection through wide-scale treatment as prevention and pre-exposure prophylaxis (PrEP). Potent tenofovir disoproxil fumarate-containing regimens are increasingly used to treat and prevent HIV, although few data exist for frequency and risk factors of acquired drug resistance in regions hardest hit by the HIV pandemic. We aimed to do a global assessment of drug resistance after virological failure with first-line tenofovir-containing ART. Methods The TenoRes collaboration comprises adult HIV treatment cohorts and clinical trials of HIV drug resistance testing in Europe, Latin and North America, sub-Saharan Africa, and Asia. We extracted and harmonised data for patients undergoing genotypic resistance testing after virological failure with a first-line regimen containing tenofovir plus a cytosine analogue (lamivudine or emtricitabine) plus a non-nucleotide reverse-transcriptase inhibitor (NNRTI; efavirenz or nevirapine). We used an individual participant-level meta-analysis and multiple logistic regression to identify covariates associated with drug resistance. Our primary outcome was tenofovir resistance, defined as presence of K65R/N or K70E/G/Q mutations in the reverse transcriptase (RT) gene. Findings We included 1926 patients from 36 countries with treatment failure between 1998 and 2015. Prevalence of tenofovir resistance was highest in sub-Saharan Africa (370/654 [57%]). Pre-ART CD4 cell count was the covariate most strongly associated with the development of tenofovir resistance (odds ratio [OR] 1·50, 95% CI 1·27–1·77 for CD4 cell count

The research question addressed in this study is the impact of the CAP 2013 reform and alternative CAP scenarios on farm investment behaviour and economic performances in different farming systems. An ex-ante analysis of the farmers’ response to different policy scenarios is performed simulating some of the main changes introduced by the reform in both CAP pillars, accounting for regional variations across Europe. The methodology consist in the implementation of a farm-level mathematical programming model. The model is cast as an integer dynamic linear programming model based on the model developed by Viaggi et al. (2010) using GAMS software. The models are calibrated using a set of real farms data and accouting for farmers stated intentions collected through survey (Lefebvre, 2014). In this paper we present the model structure, the policy scenario and the results of the simulations carried out on 50 models, each corresponding to a surveyed farm.

The energy cost of locomotion (C) is a useful tool for quantifying the level of walking disability in the clinical evaluation of patients with cerebral palsy (CP). In addition to clinical condition, also age and velocity (v) can influence C, a fact that is often overlooked.To show: i) that C differs in the clinical subtypes of CP (hemiplegia or diplegia) and ii) that C should be measured at comparable speeds in CP patients and controls (of the same age).Controlled study.Pediatric Rehabilitation Unit of "E. Medea" Scientific Institute (Conegliano, TV); Exercise Physiology Lab of University of Verona.Forty-three CP children (32 diplegic: Dg; 11 hemiplegic: Hg) and 20 healthy children (Cg) with an age range of 4-14 years.C was measured as the ratio of net oxygen uptake to walking speed (at v from 1 to 6 km·h(-1)). The Locomotory index (LI) was calculated as the ratio of C in Dg/Hg and Cg (of the same age) at the same speed.C decreases with increasing speed in all groups but evolves differently in Hg and Dg: in the former C decreases by increasing age, becoming similar to that of Cg at 12-14 years; in the latter C does not change as a function of age being always larger than in Cg.Our data highlight the reduction in C with increasing speed and suggest a better prognosis of locomotion for Hg compared to Dg.

Gait training with the help of assistive technological devices is an innovative field of research in neurological rehabilitation. Most of the available gait training devices do not allow free movement in the environment, which would be the most suitable natural and motivating condition for training children with neurological gait impairment.To evaluate the potential applicability of a new robotic walking aid as a tool for gait training in non-ambulatory children with Cerebral Palsy.Single case studyOutpatient regimenA 11-years-old child unable to stand and walk independently as a result of spastic tetraplegic cerebral palsy (CP).The experimental device was a newly actuated version of a dynamic combined walking and standing aid (NF-Walker®) available in the market which was modified by means of two pneumatic artificial muscles driven by a foot-switch inserted in the shoes. The child was tested at baseline (while maintaining the standing position aided by the non-actuated NF-Walker®) and in the experimental condition (while using the actuated robotic aid). The outcome measures were: 2-minute walking test, 10-metre walking test, respiratory and heart parameters, energy cost of locomotion.At baseline, the child was unable to perform any autonomous form of locomotion. When assisted by the actuated aid (i.e. during the experimental condition), the child was successful in moving around in his environment. His performance was 19.63 m in the 2-minute walking test and 64 s in the 10-metre walking test. Respiratory and heart parameters were higher than healthy age-matched children both at baseline and in the experimental condition. The energy cost of gait, which was not valuable in the baseline condition, was significantly higher than normality during the experimental condition.The new robotic walking aid may help children suffering from CP with severe impairment of gait to move around in their environment.This new robotic walking device may have a potential impact in stimulating the development and in training of gait in children with neurological gait impairment. Future studies are warranted in order to test this hypothesis.

Soporte magnético para la grabación y lectura de información, método de almacenamiento y lectura de información y su uso. El soporte magnético comprende un circuito magnético definido en una lámina delgada magnética con anisotropía uniaxial y un nanocomposite constituido por una red bidimensional de nanopozos asimétricos rellenos de otro material magnético de mayor coercitividad y/o anisotropía que la lámina delgada magnética. También es objeto de la invención un método de almacenamiento y lectura de información simultáneo mediante desplazamiento de paredes magnéticas y su uso en la encriptación de información. De aplicación en los sectores en los que se diseñen, produzcan o utilicen dispositivos magnéticos para el almacenamiento y lectura de información, como en los sectores de material y equipo eléctrico, electrónico y óptico, de informática, de tecnologías de la información y de la comunicación, de maquinaria y equipo mecánico, y de transportes y comunicaciones., Universidad de Oviedo, Universidad Complutense de Madrid, Consejo Superior de Investigaciones Científicas (España), Centre National de la Recherche Scientifique, A2 Solicitud de patente sin informe sobre el estado de la técnica

Several approaches have been developed to estimate age, an important aspect of forensics and orthodontics, using different measures and radiological examinations. Here, through meta-analysis, we determined the validity of age estimation methods and reproducibility of bone/dental maturity indices used for age estimation. The PubMed and Google Scholar databases were searched to December 31, 2021 for human cross-sectional studies meeting pre-defined PICOS criteria that simultaneously assessed the reproducibility and validity. Meta-estimates of validity (mean error: estimated age-chronological age) and intra- and inter-observer reproducibility (Cohen’s kappa, intraclass correlation coefficient) and their predictive intervals (PI) were calculated using mixed-effect models when heterogeneity was high (I2 > 50%). The literature search identified 433 studies, and 23 met the inclusion criteria. The mean error meta-estimate (mixed effects model) was 0.08 years (95% CI − 0.12; 0.29) in males and 0.09 (95% CI − 0.12; 0.30) in females. The PI of each method spanned zero; of nine reported estimation methods, Cameriere’s had the smallest (− 0.82; 0.47) and Haavikko’s the largest (− 7.24; 4.57) PI. The reproducibility meta-estimate (fixed effects model) was 0.98 (95% CI 0.97; 1.00) for intra- and 0.99 (95% CI 0.98; 1.00) for inter-observer agreement. All methods were valid but with different levels of precision. The intra- and inter-observer reproducibility was high and homogeneous across studies.

Summary Background Baricitinib is an oral selective Janus kinase 1/2 inhibitor with known anti-inflammatory properties. This study evaluates the efficacy and safety of baricitinib in combination with standard of care for the treatment of hospitalised adults with COVID-19. Methods In this phase 3, double-blind, randomised, placebo-controlled trial, participants were enrolled from 101 centres across 12 countries in Asia, Europe, North America, and South America. Hospitalised adults with COVID-19 receiving standard of care were randomly assigned (1:1) to receive once-daily baricitinib (4 mg) or matched placebo for up to 14 days. Standard of care included systemic corticosteroids, such as dexamethasone, and antivirals, including remdesivir. The composite primary endpoint was the proportion who progressed to high-flow oxygen, non-invasive ventilation, invasive mechanical ventilation, or death by day 28, assessed in the intention-to-treat population. All-cause mortality by day 28 was a key secondary endpoint, and all-cause mortality by day 60 was an exploratory endpoint; both were assessed in the intention-to-treat population. Safety analyses were done in the safety population defined as all randomly allocated participants who received at least one dose of study drug and who were not lost to follow-up before the first post-baseline visit. This study is registered with ClinicalTrials.gov , NCT04421027 . Findings Between June 11, 2020, and Jan 15, 2021, 1525 participants were randomly assigned to the baricitinib group (n=764) or the placebo group (n=761). 1204 (79·3%) of 1518 participants with available data were receiving systemic corticosteroids at baseline, of whom 1099 (91·3%) were on dexamethasone; 287 (18·9%) participants were receiving remdesivir. Overall, 27·8% of participants receiving baricitinib and 30·5% receiving placebo progressed to meet the primary endpoint (odds ratio 0·85 [95% CI 0·67 to 1·08], p=0·18), with an absolute risk difference of −2·7 percentage points (95% CI −7·3 to 1·9). The 28-day all-cause mortality was 8% (n=62) for baricitinib and 13% (n=100) for placebo (hazard ratio [HR] 0·57 [95% CI 0·41–0·78]; nominal p=0·0018), a 38·2% relative reduction in mortality; one additional death was prevented per 20 baricitinib-treated participants. The 60-day all-cause mortality was 10% (n=79) for baricitinib and 15% (n=116) for placebo (HR 0·62 [95% CI 0·47–0·83]; p=0·0050). The frequencies of serious adverse events (110 [15%] of 750 in the baricitinib group vs 135 [18%] of 752 in the placebo group), serious infections (64 [9%] vs 74 [10%]), and venous thromboembolic events (20 [3%] vs 19 [3%]) were similar between the two groups. Interpretation Although there was no significant reduction in the frequency of disease progression overall, treatment with baricitinib in addition to standard of care (including dexamethasone) had a similar safety profile to that of standard of care alone, and was associated with reduced mortality in hospitalised adults with COVID-19. Funding Eli Lilly and Company. Translations For the French, Japanese, Portuguese, Russian and Spanish translations of the abstract see Supplementary Materials section.

This paper focuses on the existence of temporal deixis in Indo-European, questioning the traditional view according to which metaphors of time in ancient Indo-European languages originated from projecting the human body coordinates onto space. In particular, it aims at interpreting data from historical-comparative linguistics by using the cognitive linguistic framework, without disregarding the most recent results from typological studies, spatial language acquisition, and neurolinguistic research on spatiotemporal deixis. Contrary to what previously assumed, the comparative analysis between the Rigveda and the Homeric poems shows that earlier spatial metaphors of time are still deictically neutral and anchored to the absolute Frame of Reference (FoR), which is proper to ‘objective’ temporal sequences. The tense-related Ego-perspective FoR that conventionally separates the past, the present, and the future in the more complex three-term system of temporal adverbs or spatial expressions is a later development, which is ascribed to the ‘post-archaic’ or classical stage of ancient Indo-European languages.