A proper motion study of the Lupus clouds using VO tools

Aims: By using kinematical information, we test the membership of the new Lupus candidate members proposed by the Cores to Disks (c2d) Spitzer Legacy Program program and by a complementary optical survey. We also investigate the relationship between the proper motions (pm) and other properties, in order to get some clues about their formation and early evolution. Methods: We compiled a list of members and possible members of Lupus 1, 3, and 4, together with all information on their spectral types, disks, and physical parameters. Using VO-tools, we cross-matched this list with the astrometric catalogues to get pm. Our final sample contains sources with magnitudes I<16mag and estimated masses >~0.1Msun. Results: According to the kinematic information, our sources can be divided into two main groups. The first one contains sources with higher pm in agreement with other Gould Belt populations and with spatial distribution, optical and near-infrared colours, and disk composition consistent with these objects belonging to the Lupus clouds. In the second group, sources have lower pm with random orientations, and they are mostly located outside the cloud cores, making their association with the Lupus complex more doubtful. We investigate the properties of the higher pm group, but cannot find any correlations with spatial location, binarity, the presence of a circumstellar disk, or with physical properties such as effective temperature, luminosity, mass, or age. Conclusions: We conclude that the lower pm group probably represents a background population or mixture of populations unrelated to the Lupus clouds. The higher pm group, on the other hand, has properties consistent with it being a genuine population of the Lupus star-forming region. More accurate pm and/or radial velocity information are required for a more detailed study of the kinematic properties of the Lupus stellar members.Comment: Accepted in A&

On the coherence loss in phase-referenced VLBI observations

Context: Phase referencing is a standard calibration technique in radio interferometry, particularly suited for the detection of weak sources close to the sensitivity limits of the interferometers. However, effects from a changing atmosphere and inaccuracies in the correlator model may affect the phase-referenced images, leading to wrong estimates of source flux densities and positions. A systematic observational study of signal decoherence in phase referencing, and its effects in the image plane, has not been performed yet. Aims: We systematically studied how the signal coherence in Very-Long-Baseline-Interferometry (VLBI) observations is affected by a phase-reference calibration at different frequencies and for different calibrator-to-target separations. The results obtained should be of interest for a correct interpretation of many phase-referenced observations with VLBI. Methods: We observed a set of 13 strong sources (the S5 polar cap sample) at 8.4 and 15 GHz in phase-reference mode, with 32 different calibrator/target combinations spanning angular separations between 1.5 and 20.5 degrees. We obtained phase-referenced images and studied how the dynamic range and peak flux density depend on observing frequency and source separation. Results: We obtained dynamic ranges and peak flux densities of the phase-referenced images as a function of frequency and separation from the calibrator. We compared our results with models and phenomenological equations previously reported. Conclusions: The dynamic range of the phase-referenced images is strongly limited by the atmosphere at all frequencies and for all source separations. The limiting dynamic range is inversely proportional to the sine of the calibrator-to-target separation. We also find that the peak flux densities, relative to those obtained with the self-calibrated images, decrease with source separation.Comment: 5 pages, 3 figures. Submitted to A&A on 5.02.2010; accepted on 11.03.2010

Cost-effectiveness analysis of a multiple health behaviour change intervention in people aged between 45 and 75 years: a cluster randomized controlled trial in primary care (EIRA study)

Background: Multiple health behaviour change (MHBC) interventions that promote healthy lifestyles may be an efficient approach in the prevention or treatment of chronic diseases in primary care. This study aims to evaluate the cost-utility and cost-effectiveness of the health promotion EIRA intervention in terms of MHBC and cardiovascular reduction. Methods: An economic evaluation alongside a 12-month cluster-randomised (1:1) controlled trial conducted between 2017 and 2018 in 25 primary healthcare centres from seven Spanish regions. The study took societal and healthcare provider perspectives. Patients included were between 45 and 75 years old and had any two of these three behaviours: smoking, insufficient physical activity or low adherence to Mediterranean dietary pattern. Intervention duration was 12 months and combined three action levels (individual, group and community). MHBC, defined as a change in at least two health risk behaviours, and cardiovascular risk (expressed in % points) were the outcomes used to calculate incremental cost-effectiveness ratios (ICER). Quality-adjusted life-years (QALYs) were estimated and used to calculate incremental cost-utility ratios (ICUR). Missing data was imputed and bootstrapping with 1000 replications was used to handle uncertainty in the modelling results. Results: The study included 3062 participants. Intervention costs were €295 higher than usual care costs. Five per-cent additional patients in the intervention group did a MHBC compared to usual care patients. Differences in QALYS or cardiovascular risk between-group were close to 0 (- 0.01 and 0.04 respectively). The ICER was €5598 per extra health behaviour change in one patient and €6926 per one-point reduction in cardiovascular risk from a societal perspective. The cost-utility analysis showed that the intervention increased costs and has no effect, in terms of QALYs, compared to usual care from a societal perspective. Cost-utility planes showed high uncertainty surrounding the ICUR. Sensitivity analysis showed results in line with the main analysis. Conclusion: The efficiency of EIRA intervention cannot be fully established and its recommendation should be conditioned by results on medium-long term effects. Trial registration: Clinicaltrials.gov NCT03136211. Registered 02 May 2017 – Retrospectively registered © 2021, The Author(s)

Kidins220 deficiency causes ventriculomegaly via SNX27-retromer-dependent AQP4 degradation

Several psychiatric, neurologic and neurodegenerative disorders present increased brain ventricles volume, being hydrocephalus the disease with the major manifestation of ventriculomegaly caused by the accumulation of high amounts of cerebrospinal fluid (CSF). The molecules and pathomechanisms underlying cerebral ventricular enlargement are widely unknown. Kinase D interacting substrate of 220 kDa (KIDINS220) gene has been recently associated with schizophrenia and with a novel syndrome characterized by spastic paraplegia, intellectual disability, nystagmus and obesity (SINO syndrome), diseases frequently occurring with ventriculomegaly. Here we show that Kidins220, a transmembrane protein effector of various key neuronal signalling pathways, is a critical regulator of CSF homeostasis. We observe that both KIDINS220 and the water channel aquaporin-4 (AQP4) are markedly downregulated at the ventricular ependymal lining of idiopathic normal pressure hydrocephalus (iNPH) patients. We also find that Kidins220 deficient mice develop ventriculomegaly accompanied by water dyshomeostasis and loss of AQP4 in the brain ventricular ependymal layer and astrocytes. Kidins220 is a known cargo of the SNX27-retromer, a complex that redirects endocytosed plasma membrane proteins (cargos) back to the cell surface, thus avoiding their targeting to lysosomes for degradation. Mechanistically, we show that AQP4 is a novel cargo of the SNX27-retromer and that Kidins220 deficiency promotes a striking and unexpected downregulation of the SNX27-retromer that results in AQP4 lysosomal degradation. Accordingly, SNX27 silencing decreases AQP4 levels in wild-type astrocytes whereas SNX27 overexpression restores AQP4 content in Kidins220 deficient astrocytes. Together our data suggest that the KIDINS220-SNX27-retromer-AQP4 pathway is involved in human ventriculomegaly and open novel therapeutic perspectives

Producción de ovino de carne en medio semiárido

Unpublishe

PRIMAGE project : predictive in silico multiscale analytics to support childhood cancer personalised evaluation empowered by imaging biomarkers

PRIMAGE is one of the largest and more ambitious research projects dealing with medical imaging, artificial intelligence and cancer treatment in children. It is a 4-year European Commission-financed project that has 16 European partners in the consortium, including the European Society for Paediatric Oncology, two imaging biobanks, and three prominent European paediatric oncology units. The project is constructed as an observational in silico study involving high-quality anonymised datasets (imaging, clinical, molecular, and genetics) for the training and validation of machine learning and multiscale algorithms. The open cloud-based platform will offer precise clinical assistance for phenotyping (diagnosis), treatment allocation (prediction), and patient endpoints (prognosis), based on the use of imaging biomarkers, tumour growth simulation, advanced visualisation of confidence scores, and machine-learning approaches. The decision support prototype will be constructed and validated on two paediatric cancers: neuroblastoma and diffuse intrinsic pontine glioma. External validation will be performed on data recruited from independent collaborative centres. Final results will be available for the scientific community at the end of the project, and ready for translation to other malignant solid tumours

Multiple health behaviour change primary care intervention for smoking cessation, physical activity and healthy diet in adults 45 to 75 years old (EIRA study): a hybrid effectiveness-implementation cluster randomised trial

Background: This study aimed to evaluate the effectiveness of a) a Multiple Health Behaviour Change (MHBC) intervention on reducing smoking, increasing physical activity and adherence to a Mediterranean dietary pattern in people aged 45–75 years compared to usual care; and b) an implementation strategy. Methods: A cluster randomised effectiveness-implementation hybrid trial-type 2 with two parallel groups was conducted in 25 Spanish Primary Health Care (PHC) centres (3062 participants): 12 centres (1481 participants) were randomised to the intervention and 13 (1581 participants) to the control group (usual care). The intervention was based on the Transtheoretical Model and focused on all target behaviours using individual, group and community approaches. PHC professionals made it during routine care. The implementation strategy was based on the Consolidated Framework for Implementation Research (CFIR). Data were analysed using generalised linear mixed models, accounting for clustering. A mixed-methods data analysis was used to evaluate implementation outcomes (adoption, acceptability, appropriateness, feasibility and fidelity) and determinants of implementation success. Results: 14.5% of participants in the intervention group and 8.9% in the usual care group showed a positive change in two or all the target behaviours. Intervention was more effective in promoting dietary behaviour change (31.9% vs 21.4%). The overall adoption rate by professionals was 48.7%. Early and final appropriateness were perceived by professionals as moderate. Early acceptability was high, whereas final acceptability was only moderate. Initial and final acceptability as perceived by the participants was high, and appropriateness moderate. Consent and recruitment rates were 82.0% and 65.5%, respectively, intervention uptake was 89.5% and completion rate 74.7%. The global value of the percentage of approaches with fidelity =50% was 16.7%. Eight CFIR constructs distinguished between high and low implementation, five corresponding to the Inner Setting domain. Conclusions: Compared to usual care, the EIRA intervention was more effective in promoting MHBC and dietary behaviour change. Implementation outcomes were satisfactory except for the fidelity to the planned intervention, which was low. The organisational and structural contexts of the centres proved to be significant determinants of implementation effectiveness. Trial registration: ClinicalTrials.gov, NCT03136211. Registered 2 May 2017, “retrospectively registered”. © 2021, The Author(s)

Sex and gender differences in acute stroke care: metrics, access to treatment and outcome. A territorial analysis of the Stroke Code System of Catalonia

Introduction: Previous studies have reported differences in the management and outcome of women stroke patients in comparison with men. We aim to analyze sex and gender differences in the medical assistance, access to treatment and outcome of acute stroke patients in Catalonia. Patients and methods: Data were obtained from a prospective population-based registry of stroke code activations in Catalonia (CICAT) from January/2016 to December/2019. The registry includes demographic data, stroke severity, stroke subtype, reperfusion therapy, and time workflow. Centralized clinical outcome at 90 days was assessed in patients receiving reperfusion therapy. Results: A total of 23,371 stroke code activations were registered (54% men, 46% women). No differences in prehospital time metrics were observed. Women more frequently had a final diagnosis of stroke mimic, were older and had a previous worse functional situation. Among ischemic stroke patients, women had higher stroke severity and more frequently presented proximal large vessel occlusion. Women received more frequently reperfusion therapy (48.2% vs 43.1%, p < 0.001). Women tended to present a worse outcome at 90 days, especially for the group receiving only IVT (good outcome 56.7% vs 63.8%; p < 0.001), but not for the group of patients treated with IVT + MT or MT alone, although sex was not independently associated with clinical outcome in logistic regression analysis (OR 1.07; 95% CI, 0.94–1.23; p = 0.27) nor in the analysis after matching using the propensity score (OR 1.09; 95% CI, 0.97–1.22). Discussion and conclusion: We found some differences by sex in that acute stroke was more frequent in older women and the stroke severity was higher. We found no differences in medical assistance times, access to reperfusion treatment and early complications. Worse clinical outcome at 90 days in women was conditioned by stroke severity and older age, but not by sex itself

Missense mutations in TENM4, a regulator of axon guidance and central myelination, cause essential tremor.

Essential tremor (ET) is a common movement disorder with an estimated prevalence of 5% of the population aged over 65 years. In spite of intensive efforts, the genetic architecture of ET remains unknown. We used a combination of whole-exome sequencing and targeted resequencing in three ET families. In vitro and in vivo experiments in oligodendrocyte precursor cells and zebrafish were performed to test our findings. Whole-exome sequencing revealed a missense mutation in TENM4 segregating in an autosomal-dominant fashion in an ET family. Subsequent targeted resequencing of TENM4 led to the discovery of two novel missense mutations. Not only did these two mutations segregate with ET in two additional families, but we also observed significant over transmission of pathogenic TENM4 alleles across the three families. Consistent with a dominant mode of inheritance, in vitro analysis in oligodendrocyte precursor cells showed that mutant proteins mislocalize. Finally, expression of human mRNA harboring any of three patient mutations in zebrafish embryos induced defects in axon guidance, confirming a dominant-negative mode of action for these mutations. Our genetic and functional data, which is corroborated by the existence of a Tenm4 knockout mouse displaying an ET phenotype, implicates TENM4 in ET. Together with previous studies of TENM4 in model organisms, our studies intimate that processes regulating myelination in the central nervous system and axon guidance might be significant contributors to the genetic burden of this disorder