On perturbations of Dirac operators with variable magnetic field of constant direction

We carry out the spectral analysis of matrix valued perturbations of 3-dimensional Dirac operators with variable magnetic field of constant direction. Under suitable assumptions on the magnetic field and on the pertubations, we obtain a limiting absorption principle, we prove the absence of singular continuous spectrum in certain intervals and state properties of the point spectrum. Various situations, for example when the magnetic field is constant, periodic or diverging at infinity, are covered. The importance of an internal-type operator (a 2-dimensional Dirac operator) is also revealed in our study. The proofs rely on commutator methods.Comment: 12 page

Point prevalence of surgical checklist use in Europe: relationship with hospital mortality

Background The prevalence of use of the World Health Organization surgical checklist is unknown. The clinical effectiveness of this intervention in improving postoperative outcomes is debated. Methods We undertook a retrospective analysis of data describing surgical checklist use from a 7 day cohort study of surgical outcomes in 28 European nations (European Surgical Outcomes Study, EuSOS). The analysis included hospitals recruiting >10 patients and excluding outlier hospitals above the 95th centile for mortality. Multivariate logistic regression and three-level hierarchical generalized mixed models were constructed to explore the relationship between surgical checklist use and hospital mortality. Findings are presented as crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs). Results A total of 45 591 patients from 426 hospitals were included in the analysis. A surgical checklist was used in 67.5% patients, with marked variation across countries (0-99.6% of patients). Surgical checklist exposure was associated with lower crude hospital mortality (OR 0.84, CI 0.75-0.94; P=0.002). This effect remained after adjustment for baseline risk factors in a multivariate model (adjusted OR 0.81, CI 0.70-0.94; P<0.005) and strengthened after adjusting for variations within countries and hospitals in a three-level generalized mixed model (adjusted OR 0.71, CI 0.58-0.85; P<0.001). Conclusions The use of surgical checklists varies across European nations. Reported use of a checklist was associated with lower mortality. This observation may represent a protective effect of the surgical checklist itself, or alternatively, may be an indirect indicator of the quality of perioperative care. Clinical trial registration The European Surgical Outcomes Study is registered with ClinicalTrials.gov, number NCT0120360

Development and validation of a multivariable prediction model of spontaneous preterm delivery and microbial invasion of the amniotic cavity in women with preterm labor

BACKGROUND: Early spontaneous preterm delivery is often associ- ated with microbial invasion of the amniotic cavity and/or intraamniotic inflammation. OBJECTIVE: The objective of the study was to develop and validate clinically feasible multivariable prediction models of spontaneous delivery within 7 days and microbial invasion of the amniotic cavity in women admitted with diagnose of preterm labor and intact membranes below 34 weeks. STUDY DESIGN: We used data from a cohort of women admitted from 2012 to 2018 with diagnosis of preterm labor below 34 weeks who had undergone amniocentesis to rule out microbial invasion of the amniotic cavity. The main outcome was spontaneous delivery within 7 days from admission. The secondary outcome was microbial invasion of the amniotic cavity, defined by a positive culture and/or 16S ribosomal RNA gene in the amniotic fluid. The sample (n 1⁄4 358) was divided into derivation (2012e2016) and validation cohorts (2017e2018). Logistic regression models using a stepwise selection of variables were developed for the outcomes evaluated. We explored as predictive variables ultrasound cervical length measurement at admission, maternal C-reactive protein, gestational age, amniotic fluid glucose, and interleukin-6 (expressed as log units). Models were developed in the derivation cohort and applied to the validation cohort and diagnostic performance was calculated. RESULTS: The derivation cohort included 263 women and the valida- tion cohort 95 women. One hundred five of the women (39%, 105 of 268) spontaneously delivered in the following 7 days and 68 (19%, 68 of 358) had microbial invasion of the amniotic cavity. For spontaneous delivery within 7 days after admission, 4 predictors were identified: cervical length at admission, gestational age, amniotic fluid glucose, and interleukin-6. The diagnostic performance of the model was assessed in the validation cohort using the receiver operating characteristic curve and showed an area under curve of 0.86 (95% confidence interval, 0.77e0.95) with a detection rate of spontaneous delivery within 7 days of 87%, a false- positive rate of 33%, a negative predictive value of 80%, and a negative likelihood ratio of 0.1908. For microbial invasion of the amniotic cavity, 2 independent predictors of the amniotic cavity were identified: amniotic fluid glucose and maternal C-reactive protein. The receiver operating characteristic curve and an area under curve in the validation cohort was 0.83 (95% confidence interval, 0.70e0.96) with a detection rate of 76%, a false-positive rate of 8%, a negative predictive value of 93%, and a negative likelihood ratio of 0.2591. CONCLUSION: In women with preterm labor, we propose 2 clinically feasible prediction models to classify as low vs high risk of spontaneous delivery within 7 days and of microbial invasion of the amniotic cavity. The models showed a high diagnostic performance and could be of value to optimize clinical management

Does ALS-FUS without FUS mutation represent ALS-FET? Report of three cases

Altres ajuts: This study was partially funded by Fundacio Marató de TV3 (grant no. 20143810 to RSV, no. 20141610 to EG and no. 201437.10 to RRG) and Fondo Europeo de Desarrollo Regional (FEDER) (PI16/01673 to JG and PI15/01618 to RRG). We are indebted to the Neurological Tissue Bank of the Biobanc-Hospital Clinic-IDIBAPS, Barcelona, Spain, for data and sample procurement. We thank Sara Charif, Veronica Santiago, Carmen Schweiger, Leire Etxarri and Abel Muñoz for technical assistance

Análisis de la situación de partida para la transformación del entorno educativo y familiar mediante la alfabetización digital : prueba piloto en una escuela del sistema educativo andorrano

El presente trabajo de investigación analiza la incorporación de ordenadores personales de uso individual de manera permanente en el aula y describe la situación de partida del cuanto al entorno familiar de los niños/as y su competencia TIC (Tecnologías de la información y la comunicación), con el objetivo de construir el marco a partir del cual se puede analizar, en una segunda fase, los cambios que se produzcan como influencia de la introducción de las TIC. El proyecto se desarrolla en dos aulas de primer ciclo de primera enseñanza (primaria) de la Escuela Andorrana (entre 6 y 8 años) y se obtiene una primera aproximación del uso potencial de las TIC en el entorno educativo.The present research analyse the incorporation of personal computers for individual use in the classroom and describe the initial situation in children’s family background and children’s digital skills, to build the framework where we could analyze in a second phase, the changes that occur as influenced by the introduction of ICT. The project is developed in two classrooms of a elementary school from Andorran education system (6 to 8 years old) and gives a first approximation of the potential use of ICT in educational settings

Preclinical studies with glioblastoma brain organoid co-cultures show efficient 5-ALA photodynamic therapy

Abstract: Background: The high recurrence of glioblastoma (GB) that occurs adjacent to the resection cavity within two years of diagnosis urges an improvement of therapies oriented to GB local control. Photodynamic therapy (PDT) has been proposed to cleanse infiltrating tumor cells from parenchyma to ameliorate short long-term progression-free survival. We examined 5-aminolevulinic acid (5-ALA)- mediated PDT effects as therapeutical treatment and determined optimal conditions for PDT efficacy without causing phototoxic injury to the normal brain tissue. Methods: We used a platform of Glioma Initiation Cells (GICs) infiltrating cerebral organoids with two different glioblastoma cells, GIC7 and PG88. We measured GICs-5-ALA uptake and PDT/5-ALA activity in dose-response curves and the efficacy of the treatment by measuring proliferative activity and apoptosis. Results: 5-ALA (50 and 100  g/mL) was applied, and the release of protoporphyrin IX (PpIX) fluorescence measures demonstrated that the emission of PpIX increases progressively until its stabilization at 24 h. Moreover, decreased proliferation and increased apoptosis corroborated the effect of 5-ALA/PDT on cancer cells without altering normal cells. Conclusions: We provide evidence about the effectiveness of PDT to treat high proliferative GB cells in a complex in vitro system, which combines normal and cancer cells and is a useful tool to standardize new strategic therapies

Sporadic Creutzfeldt-Jakob disease VM1: phenotypic and molecular characterization of a novel subtype of human prion disease

The methionine (M)-valine (V) polymorphic codon 129 of the prion protein gene (PRNP) plays a central role in both susceptibility and phenotypic expression of sporadic Creutzfeldt-Jakob diseases (sCJD). Experimental transmissions of sCJD in humanized transgenic mice led to the isolation of five prion strains, named M1, M2C, M2T, V2, and V1, based on two major conformations of the pathological prion protein (PrPSc, type 1 and type 2), and the codon 129 genotype determining susceptibility and propagation efficiency. While the most frequent sCJD strains have been described in codon 129 homozygosis (MM1, MM2C, VV2) and heterozygosis (MV1, MV2K, and MV2C), the V1 strain has only been found in patients carrying VV. We identified six sCJD cases, 4 in Catalonia and 2 in Italy, carrying MV at PRNP codon 129 in combination with PrPSc type 1 and a new clinical and neuropathological profile reminiscent of the VV1 sCJD subtype rather than typical MM1/MV1. All patients had a relatively long duration (mean of 20.5 vs. 3.5 months of MM1/MV1 patients) and lacked electroencephalographic periodic sharp-wave complexes at diagnosis. Distinctive histopathological features included the spongiform change with vacuoles of larger size than those seen in sCJD MM1/MV1, the lesion profile with prominent cortical and striatal involvement, and the pattern of PrPSc deposition characterized by a dissociation between florid spongiform change and mild synaptic deposits associated with coarse, patch-like deposits in the cerebellar molecular layer. Western blot analysis of brain homogenates revealed a PrPSc type 1 profile with physicochemical properties reminiscent of the type 1 protein linked to the VV1 sCJD subtype. In summary, we have identified a new subtype of sCJD with distinctive clinicopathological features significantly overlapping with those of the VV1 subtype, possibly representing the missing evidence of V1 sCJD strain propagation in the 129MV host genotype

Assessment of an intervention to optimise antenatal management of women admitted with preterm labour and intact membranes using amniocentesis-based predictive risk models: study protocol for a randomised controlled trial (OPTIM-PTL Study).

Introduction: The majority of women admitted with threatened preterm labour (PTL) do not delivery prematurely. While those with microbial invasion of the amniotic cavity (MIAC) represent the highest risk group, this is a condition that is not routinely ruled out since it requires amniocentesis. Identification of low-risk or high-risk cases might allow individualisation of care, that is, reducing overtreatment with corticosteroids and shorten hospital stay in low-risk women, while allowing early antibiotic therapy in those with MIAC. Benefits versus risks of amniocentesis-based predictor models of spontaneous delivery within 7 days and/or MIAC have not been evaluated. Methods and analysis: This will be a Spanish randomised, multicentre clinical trial in singleton pregnancies (23.0-34.6 weeks) with PTL, conducted in 13 tertiary centres. The intervention arm will consist in the use of amniocentesis-based predictor models: if low risk, hospital discharge within 24 hours of results with no further medication will be recommended. If high risk, antibiotics will be added to standard management. The control group will be managed according to standard institutional protocols, without performing amniocentesis for this indication. The primary outcome will be total antenatal doses of corticosteroids, and secondary outcomes will be days of maternal stay and the occurrence of clinical chorioamnionitis. A cost analysis will be undertaken. To observe a reduction from 90% to 70% in corticosteroid doses, a reduction in 1 day of hospital stay (SD of 2) and a reduction from 24% to 12% of clinical chorioamnionitis, a total of 340 eligible patients randomised 1 to 1 to each study arm is required (power of 80%, with type I error α=0.05 and two-sided test, considering a dropout rate of 20%). Randomisation will be stratified by gestational age and centre

Homozygous R136S mutation in PRNP gene causes inherited early onset prion disease

Altres ajuts: Fundació la Marató de TV3/201821-31Background: More than 40 pathogenic heterozygous PRNP mutations causing inherited prion diseases have been identified to date. Recessive inherited prion disease has not been described to date. Methods: We describe the clinical and neuropathological data of inherited early-onset prion disease caused by the rare PRNP homozygous mutation R136S. In vitro PrP propagation studies were performed using recombinant-adapted protein misfolding cyclic amplification technique. Brain material from two R136S homozygous patients was intracranially inoculated in TgMet129 and TgVal129 transgenic mice to assess the transmissibility of this rare inherited form of prion disease. Results: The index case presented symptoms of early-onset dementia beginning at the age of 49 and died at the age of 53. Neuropathological evaluation of the proband revealed abundant multicentric PrP plaques and Western blotting revealed a ~ 8 kDa protease-resistant, unglycosylated PrP fragment, consistent with a Gerstmann-Sträussler-Scheinker phenotype. Her youngest sibling suffered from progressive cognitive decline, motor impairment, and myoclonus with onset in her late 30s and died at the age of 48. Genetic analysis revealed the presence of the R136S mutation in homozygosis in the two affected subjects linked to homozygous methionine at codon 129. One sibling carrying the heterozygous R136S mutation, linked to homozygous methionine at codon 129, is still asymptomatic at the age of 74. The inoculation of human brain homogenates from our index case and an independent case from a Portuguese family with the same mutation in transgenic mice expressing human PrP and in vitro propagation of PrP studies failed to show disease transmissibility. Conclusion: In conclusion, biallelic R136S substitution is a rare variant that produces inherited early-onset human prion disease with a Gerstmann-Sträussler-Scheinker neuropathological and molecular signature. Even if the R136S variant is predicted to be "probably damaging", heterozygous carriers are protected, at least from an early onset providing evidence for a potentially recessive pattern of inheritance in human prion diseases

Complex multiple risk intervention to promote healthy behaviours in people between 45 to 75 years attended in primary health care (EIRA study): study protocol for a hybrid trial

CDATA[CDATA[Background: Health promotion is a key process of current health systems Primary Health Care (PHC) is the ideal setting for health promotion but multifaceted barriers make its integration difficult in the usual care. The majority of the adult population engages two 01 more risk behaviours, that is why a multiple intervention might be more effective and efficient The primary objectives are to evaluate the effectiveness, the cost effectiveness and an implementation strategy of a complex multiple risk intervention to promote healthy behaviours in people between 45 to 75 years attended in PHC. CDATA[CDATA[Methods: This study is a cluster randomised controlled hybrid type 2 trial with two parallel groups comparing a complex multiple risk behaviour intervention with usual care It will be carried out in 26 PHC centres in Spam The study focuses on people between 45 and 75 years who carry out two or more of the following unhealthy behaviours tobacco use, low adherence to the Mediterranean dietary pattern or insufficient physical activity level The intervention is based on the Transtheoretical Model and it will be made by physicians and nurses in the routine care of PHC practices according to the conceptual framework of the ''5A''s" It will have a maximum duration of 12 months and it will be carried out to three different levels (individual, group and community) Incremental cost per quality adjusted life year gamed measured by the tanffs of the EuioQo! 5D questionnaire will be estimated. The implementation strategy is based on the ''Consolidated Framework for Implementation Research, a set of discrete implementation strategies and an evaluation framework. CDATA[CDATA[Discussion: EIRA study will determine the effectiveness and cost effectiveness of a complex multiple risk intervention and will provide a better understanding of implementation processes of health promotion interventions in PHC setting. It may contribute to increase knowledge about the individual and structural barriers that affect implementation of these interventions and to quantify the contextual factors that moderate the effectiveness of implementation