Fabrication of gold nanowires on insulating substrates by field-induced mass transport

A method for the fabrication of nanometer size gold wires on insulating surfaces is presented. An oscillating gold-coated atomic force microscope tip is brought into close proximity of a silicon dioxide surface. The application of a negative sample voltage produces the transport of gold atoms from the tip to the surface. The voltage is applied when there is a tip–surface separation of ∼3 nm. The finite tip–surface separation enhances the tip lifetime. It also allows the application of sequences of multiple voltage pulses. Those sequences allow the fabrication of continuous nanowires. The atomic force microscope gold deposition is performed at room temperature and in ambient conditions which makes the method fully compatible with standard lithographic techniques. Electron transport measurements of the wires show a clear metallic behavior. Electrical resistivities of ∼ 3×10−7 Ω m and current densities of up to 5×1011 A m−2 are reported.This work was supported by the Dirección General de Enseñanza Superior e Investigación (PB98-0471) and the European Commission (MONA-LISA, GRD1-2000-25592). One of the authors (M.C.) acknowledges financial support from the Comunidad de Madrid.Peer reviewe

Modification of AFM tips by depositing nanoparticles with an Ion Cluster Source. Enhancement of the aspect-ratio and lateral resolution

Póster presentado en la NanoSpain Conference (Nanoiberian Conference), celebrada en Bilbao del 11 al 14 de abril de 2011.One of the factors that limit the spatial resolution in atomic force microscopy (AFM) is the physical size of the probe. This limitation is particularly severe when the imaged structures are comparable in size to the tip¿s apex. The resolution in the AFM is usually enhanced by using sharp tips with high aspect ratios. In the present paper we propose an approach to modify AFM tips that consists of depositing nanoclusters on standard silicon tips. We show that the use of those tips leads to atomic force microscopy images of higher aspect ratios and spatial resolution. The present approach has two major properties. It provides higher aspect-ratio images of nanoscale objects and, at the same time, enables to functionalize the AFM tips by depositing nanoparticles with well-controlled chemical composition.Peer Reviewe

Aspect-ratio and lateral-resolution enhancement in force microscopy by attaching nanoclusters generated by an ion cluster source at the end of a silicon tip

One of the factors that limit the spatial resolution in atomic force microscopy (AFM) is the physical size of the probe. This limitation is particularly severe when the imaged structures are comparable in size to the tip’s apex. The resolution in the AFM is usually enhanced by using sharp tips with high aspect ratios. In the present paper we propose an approach to modify AFM tips that consists of depositing nanoclusters on standard silicon tips. We show that the use of those tips leads to atomic force microscopy images of higher aspect ratios and spatial resolution. The present approach has two major properties. It provides higher aspect-ratio images of nanoscale objects and, at the same time, enables to functionalize the AFM tips by depositing nanoparticles with well-controlled chemical composition.The authors acknowledge the Spanish Ministerio de Ciencia e Innovación and Comisión Interministerial para la Ciencia Y la Tecnología—CICYT under Contract Nos. MAT2008-06765-C02-02, MAT2009-08650, and CSD2007 00041 (Nanoselect) and through the FPI and “Juan de La Cierva” programs for financial support.Peer reviewe

Impaired proteasome activity and neurodegeneration with brain iron accumulation in FBXO7 defect

Altres ajuts: This work was funded by Instituto de Salud Carlos III; Ministerio de Educación, Cultura y Deporte; Spanish Foundation per Amor a l'Art (FPAA) grant ; Fundació la Marató de TV3 grants 20143130; and 20143131; Generalitat Valenciana grants OP ERDF of Comunitat Valenciana 2014-2020; and PROMETEO/2018/135.FBXO7 is implicated in the ubiquitin-proteasome system and parkin-mediated mitophagy. FBXO7defects cause a levodopa-responsive parkinsonian-pyramidal syndrome(PPS). Methods: We investigated the disease molecular bases in a child with PPS and brain iron accumulation. Results: A novel homozygous c.368C>G (p.S123*) FBXO7 mutation was identified in a child with spastic paraplegia, epilepsy, cerebellar degeneration, levodopa nonresponsive parkinsonism, and brain iron deposition. Patient's fibroblasts assays demonstrated an absence of FBXO7 RNA expression leading to impaired proteasome degradation and accumulation of poly-ubiquitinated proteins. Conclusion: This novel FBXO7 phenotype associated with impaired proteasome activity overlaps with neurodegeneration with brain iron accumulation disorders

Point-of-care lung ultrasound assessment for risk stratification and therapy guiding in COVID-19 patients. A prospective non-interventional study.

Background Lung ultrasound is feasible for assessing lung injury caused by coronavirus disease 2019 (COVID-19). However, the prognostic meaning and time-line changes of lung injury assessed by lung ultrasound in COVID-19 hospitalised patients are unknown. Methods Prospective cohort study designed to analyse prognostic value of lung ultrasound in COVID-19 patients by using a quantitative scale (lung ultrasound Zaragoza (LUZ)-score) during the first 72 h after admission. The primary end-point was in-hospital death and/or admission to the intensive care unit. Total length of hospital stay, increase of oxygen flow and escalation of medical treatment during the first 72 h were secondary end-points. Results 130 patients were included in the final analysis; mean±sd age was 56.7±13.5 years. Median (interquartile range) time from the beginning of symptoms to admission was 6 (4–9) days. Lung injury assessed by LUZ-score did not differ during the first 72 h (21 (16–26) points at admission versus 20 (16–27) points at 72 h; p=0.183). In univariable logistic regression analysis, estimated arterial oxygen tension/inspiratory oxygen fraction ratio (PAFI) (hazard ratio 0.99, 95% CI 0.98–0.99; p=0.027) and LUZ-score >22 points (5.45, 1.42–20.90; p=0.013) were predictors for the primary end-point. Conclusions LUZ-score is an easy, simple and fast point-of-care ultrasound tool to identify patients with severe lung injury due to COVID-19, upon admission. Baseline score is predictive of severity along the whole period of hospitalisation. The score facilitates early implementation or intensification of treatment for COVID-19 infection. LUZ-score may be combined with clinical variables (as estimated by PAFI) to further refine risk stratification

Effect of sex in systemic psoriasis therapy: Differences in prescription, effectiveness and safety in the BIOBADADERM prospective cohort

The effect of sex on systemic therapy for psoriasis has not been well studied. The aim of this study was to analyse a large multicentre Spanish cohort of 2,881 patients with psoriasis (58.3% males), followed from January 2008 to November 2018, to determine whether sex influences prescription, effectiveness of therapy, and the risk of adverse events. The results show that women are more likely than men to be pre-scribed biologics. There were no differences between men and women in effectiveness of therapy, measur-ed in terms of drug survival. Women were more likely to develop adverse events, but the difference in risk was small and does not justify different management. Study limitations include residual confounding and the use of drug survival as a proxy for effectiveness.The BIOBADADERM project is promoted by the Fundación Piel Sana Academia Española de Dermatología y Venereología, which receives financial support from the Spanish Medicines and Health Products Agency (Agencia Española de Medicamentos y Productos Sanitarios) and from pharmaceutical companies (Abbott/Abbvie, Pfizer, MSD, Novartis, Lilly, Janssen and Almirall)

Determinación de procesos de fractura sobre huesos frescos: un sistema de análisis de los ángulos de los planos de fracturación como discriminador de agentes bióticos

The breakage planes of bones have diversely been used to classify breakage patterns. However, no diagnosis seems to be currently valid to differentiate between humans and carnivores as the main breaking agents. This work presents the results of experimentation focused on the analysis of the angles of each plane between the cortical and medullary surfaces resulting from breakage. It is shown that this approach can be fairly resolutive since both types of agents break bones through different physical processes (percussion and pression) which produce different angles in each fracture episode, as a result of the use of dynamic and static loading processes.Los paños de fractura de los huesos siempre se han prestado a diversos análisis de clasificación, pero con menor éxito se ha podido averiguar el (los) agente(s) responsable( s) de su ruptura. De los diversos atributos utilizados, uno de ellos (los ángulos de los planos de fractura) se ha sometido a exhaustivo análisis, con los resultados que se ofrecen en el presente trabajo. Se concluye que dichos ángulos, en su consideración global en una muestra pueden ser resolutivos ya que los diversos agentes bióticos que rompen huesos (humanos y carnívoros) lo hacen por procesos físicos distintos (percusión y presión) que provocan diagnosis diferenciadas en el modo en que los huesos aparecen fracturados

Effectiveness of a strategy that uses educational games to implement clinical practice guidelines among Spanish residents of family and community medicine (e-EDUCAGUIA project):A clinical trial by clusters

This study was funded by the Fondo de Investigaciones Sanitarias FIS Grant Number PI11/0477 ISCIII.-REDISSEC Proyecto RD12/0001/0012 AND FEDER Funding.Background: Clinical practice guidelines (CPGs) have been developed with the aim of helping health professionals, patients, and caregivers make decisions about their health care, using the best available evidence. In many cases, incorporation of these recommendations into clinical practice also implies a need for changes in routine clinical practice. Using educational games as a strategy for implementing recommendations among health professionals has been demonstrated to be effective in some studies; however, evidence is still scarce. The primary objective of this study is to assess the effectiveness of a teaching strategy for the implementation of CPGs using educational games (e-learning EDUCAGUIA) to improve knowledge and skills related to clinical decision-making by residents in family medicine. The primary objective will be evaluated at 1 and 6months after the intervention. The secondary objectives are to identify barriers and facilitators for the use of guidelines by residents of family medicine and to describe the educational strategies used by Spanish teaching units of family and community medicine to encourage implementation of CPGs. Methods/design: We propose a multicenter clinical trial with randomized allocation by clusters of family and community medicine teaching units in Spain. The sample size will be 394 residents (197 in each group), with the teaching units as the randomization unit and the residents comprising the analysis unit. For the intervention, both groups will receive an initial 1-h session on clinical practice guideline use and the usual dissemination strategy by e-mail. The intervention group (e-learning EDUCAGUIA) strategy will consist of educational games with hypothetical clinical scenarios in a virtual environment. The primary outcome will be the score obtained by the residents on evaluation questionnaires for each clinical practice guideline. Other included variables will be the sociodemographic and training variables of the residents and the teaching unit characteristics. The statistical analysis will consist of a descriptive analysis of variables and a baseline comparison of both groups. For the primary outcome analysis, an average score comparison of hypothetical scenario questionnaires between the EDUCAGUIA intervention group and the control group will be performed at 1 and 6months post-intervention, using 95% confidence intervals. A linear multilevel regression will be used to adjust the model. Discussion: The identification of effective teaching strategies will facilitate the incorporation of available knowledge into clinical practice that could eventually improve patient outcomes. The inclusion of information technologies as teaching tools permits greater learning autonomy and allows deeper instructor participation in the monitoring and supervision of residents. The long-term impact of this strategy is unknown; however, because it is aimed at professionals undergoing training and it addresses prevalent health problems, a small effect can be of great relevance. Trial registration: ClinicalTrials.gov: NCT02210442.Publisher PDFPeer reviewe

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe