Generalized Green's functions for higher order boundary value matrix differential systems

In this paper, a Green's matrix function for higher order two point boundary value differential matrix problems is constructed. By using the concept of rectangular co-solution of certain algebraic matrix equation associated to the problem, an existence condition as well as an explicit closed form expression for the solution of possibly not well-posed boundary value problems is given avoiding the increase of the problem dimension

An optimized methodology for whole genome sequencing of RNA respiratory viruses from nasopharyngeal aspirates

Over the last decade, the number of viral genome sequences deposited in available databases has grown exponentially. However, sequencing methodology vary widely and many published works have relied on viral enrichment by viral culture or nucleic acid amplification with specific primers rather than through unbiased techniques such as metagenomics. The genome of RNA viruses is highly variable and these enrichment methodologies may be difficult to achieve or may bias the results. In order to obtain genomic sequences of human respiratory syncytial virus (HRSV) from positive nasopharyngeal aspirates diverse methodologies were evaluated and compared. A total of 29 nearly complete and complete viral genomes were obtained. The best performance was achieved with a DNase I treatment to the RNA directly extracted from the nasopharyngeal aspirate (NPA), sequence-independent single-primer amplification (SISPA) and library preparation performed with Nextera XT DNA Library Prep Kit with manual normalization. An average of 633,789 and 1,674,845 filtered reads per library were obtained with MiSeq and NextSeq 500 platforms, respectively. The higher output of NextSeq 500 was accompanied by the increasing of duplicated reads percentage generated during SISPA (from an average of 1.5% duplicated viral reads in MiSeq to an average of 74% in NextSeq 500). HRSV genome recovery was not affected by the presence or absence of duplicated reads but the computational demand during the analysis was increased. Considering that only samples with viral load E+06 copies/ml NPA were tested, no correlation between sample viral loads and number of total filtered reads was observed, nor with the mapped viral reads. The HRSV genomes showed a mean coverage of 98.46% with the best methodology. In addition, genomes of human metapneumovirus (HMPV), human rhinovirus (HRV) and human parainfluenza virus types 1–3 (HPIV1-3) were also obtained with the selected optimal methodology.Fil: Goya, Stephanie. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Valinotto, Laura Elena. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Tittarelli, Estefanía. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rojo, Gabriel Lihue. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Nabaes Jodar, Mercedes Soledad. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Greninger, Alexander L.. University of Washington; Estados UnidosFil: Zaiat, Jonathan Javier. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Marti, Marcelo Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mistchenko, Alicia Susana. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; ArgentinaFil: Viegas, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentin

Green's Matrix for a Second Order Self-Adjoint Matrix Differential Operator

A systematic construction of the Green's matrix for a second order, self-adjoint matrix differential operator from the linearly independent solutions of the corresponding homogeneous differential equation set is carried out. We follow the general approach of extracting the Green's matrix from the Green's matrix of the corresponding first order system. This construction is required in the cases where the differential equation set cannot be turned to an algebraic equation set via transform techniques.Comment: 19 page

Fixed-ratio combination of insulin degludec and liraglutide (IDegLira) improves cardiovascular risk markers in patients with type 2 diabetes uncontrolled on basal insulin

In this post hoc analysis we investigated the effects of insulin degludec/liraglutide fixed-ratio combination (IDegLira) versus comparators on cardiovascular (CV) risk markers in participants in the DUAL II (vs. insulin degludec), DUAL V (vs. insulin glargine 100 units/mL) and DUAL VII (vs. basal-bolus therapy) trials, grouped by sex, age (<65 years, ≥65 years) and diabetes duration (<10 years, ≥10 years). Treatment contrasts were in favour of IDegLira in many subgroups for changes from baseline in glycated haemoblogin (DUAL II, DUAL V), body weight (all three trials), systolic blood pressure (BP; all three trials), HDL cholesterol (DUAL VII) and LDL cholesterol (DUAL II, DUAL V). Higher heart rates were seen with IDegLira versus comparators (all three trials) plus significantly higher diastolic BP in men (DUAL V). Differences in treatment effect were seen between sexes in waist circumference (DUAL II), systolic BP (DUAL II, DUAL V) and triglycerides (DUAL VII), and between diabetes durations in LDL cholesterol (DUAL V). In conclusion, IDegLira is associated with a general improvement in CV risk markers compared with basal insulin or basal-bolus therapy after 26 weeks of treatment

Virtual reality-based early neurocognitive stimulation in critically ill patients: A pilot randomized clinical trial

This study focuses on the application of a non-immersive virtual reality (VR)-based neurocognitive intervention in critically ill patients. Our aim was to assess the feasibility of direct outcome measures to detect the impact of this digital therapy on patients’ cognitive and emotional outcomes. Seventy-two mechanically ventilated adult patients were randomly assigned to the “treatment as usual” (TAU, n = 38) or the “early neurocognitive stimulation” (ENRIC, n = 34) groups. All patients received standard intensive care unit (ICU) care. Patients in the ENRIC group also received adjuvant neurocognitive stimulation during the ICU stay. Outcome measures were a full neuropsychological battery and two mental health questionnaires. A total of 42 patients (21 ENRIC) completed assessment one month after ICU discharge, and 24 (10 ENRIC) one year later. At onemonth follow-up, ENRIC patients had better working memory scores (p = 0.009, d = 0.363) and showed up to 50% less non-specific anxiety (11.8% vs. 21.1%) and depression (5.9% vs. 10.5%) than TAU patients. A general linear model of repeated measures reported a main effect of group, but not of time or group–time interaction, on working memory, with ENRIC patients outperforming TAU patients (p = 0.008, ¿p2 = 0.282). Our results suggest that non-immersive VR-based neurocognitive stimulation may help improve short-term working memory outcomes in survivors of critical illness. Moreover, this advantage could be maintained in the long term. An efficacy trial in a larger sample of participants is feasible and must be conducted. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Cost-Utility Analysis of a Medication Review with Follow-Up Service for Older Adults with Polypharmacy in Community Pharmacies in Spain: The conSIGUE Program

© 2015, Springer International Publishing Switzerland. Background: The concept of pharmaceutical care is operationalized through pharmaceutical professional services, which are patient-oriented to optimize their pharmacotherapy and to improve clinical outcomes. Objective: The objective of this study was to estimate the incremental cost-effectiveness ratio (ICER) of a medication review with follow-up (MRF) service for older adults with polypharmacy in Spanish community pharmacies against the alternative of having their medication dispensed normally. Methods: The study was designed as a cluster randomized controlled trial, and was carried out over a time horizon of 6 months. The target population was older adults with polypharmacy, defined as individuals taking five or more medicines per day. The study was conducted in 178 community pharmacies in Spain. Cost-utility analysis adopted a health service perspective. Costs were in euros at 2014 prices and the effectiveness of the intervention was estimated as quality-adjusted life-years (QALYs). In order to analyze the uncertainty of ICER results, we performed a non-parametric bootstrapping with 5000 replications. Results: A total of 1403 older adults, aged between 65 and 94 years, were enrolled in the study: 688 in the intervention group (IG) and 715 in the control group (CG). By the end of the follow-up, both groups had reduced the mean number of prescribed medications they took, although this reduction was greater in the IG (0.28 ± 1.25 drugs; p < 0.001) than in the CG (0.07 ± 0.95 drugs; p = 0.063). Older adults in the IG saw their quality of life improved by 0.0528 ± 0.20 (p < 0.001). In contrast, the CG experienced a slight reduction in their quality of life: 0.0022 ± 0.24 (p = 0.815). The mean total cost was €977.57 ± 1455.88 for the IG and €1173.44 ± 3671.65 for the CG. In order to estimate the ICER, we used the costs adjusted for baseline medications and QALYs adjusted for baseline utility score, resulting in a mean incremental total cost of −€250.51 ± 148.61 (95 % CI −541.79 to 40.76) and a mean incremental QALY of 0.0156 ± 0.004 (95 % CI 0.008–0.023). Regarding the results from the cost-utility analysis, the MRF service emerged as the dominant strategy. Conclusion: The MRF service is an effective intervention for optimizing prescribed medication and improving quality of life in older adults with polypharmacy in community pharmacies. The results from the cost-utility analysis suggest that the MRF service is cost effective

Adaptogenic and nootropic activities of aqueous extract of Vitis vinifera (grape seed): an experimental study in rat model

BACKGROUND: The aerial parts of Vitis vinifera (common grape or European grape) have been widely used in Ayurveda to treat a variety of common and stress related disorders. In the present investigation, the seed extract of V. vinifera was evaluated for antistress activity in normal and stress induced rats. Furthermore, the extract was studied for nootropic activity in rats and in-vitro antioxidant potential to correlate its antistress activity. METHODS: For the evaluation of antistress activity, groups of rats (n = 6) were subjected to forced swim stress one hour after daily treatment of V. vinifera extract. Urinary vanillylmandelic acid (VMA) and ascorbic acid were selected as non-invasive biomarkers to assess the antistress activity. The 24 h urinary excretion of vanillylmandelic acid (VMA) and ascorbic acid were determined by spectrophotometric methods in all groups under normal and stressed conditions. The nootropic activity of the extract as determined from acquisition, retention and retrieval in rats was studied by conditioned avoidance response using Cook's pole climbing apparatus. The in vitro antioxidant activity was determined based on the ability of V. vinifera to scavenge hydroxyl radicals. RESULTS: Daily administration of V. vinifera at doses of 100, 200 and 300 mg/kg body weight one hour prior to induction of stress inhibited the stress induced urinary biochemical changes in a dose dependent manner. However, no change in the urinary excretion of VMA and ascorbic acid was observed in normal animals at all the doses studied. The cognition, as determined by the acquisition, retention and recovery in rats was observed to be dose dependent. The extract also produced significant inhibition of hydroxyl radicals in comparison to ascorbic acid in a dose dependent manner. CONCLUSION: The present study provides scientific support for the antistress (adaptogenic), antioxidant and nootropic activities of V. vinifera seed extract and substantiate the traditional claims for the usage of grape fruits and seeds in stress induced disorders

Promoting physical activity at the school playground: A quasi-experimental intervention study

In looking for new strategies to promote physical activity (PA), the purpose of this study was to determine whether providing equipment, playground markings, and a physical education (PE)-based intervention effectively increases PA levels during school recess. A total of 223 children (mean age = 7.10 years ± 0.6; 45.3% female) from three schools participated in this study in 2012. In the first intervention school (G1; n = 75) six previous PE classes teaching games for recess were performed and playground markings and game equipment were provided. In the second intervention school (G2; n = 68) only playground markings and game equipment were provided. The third school served as the control group (GC; n = 80). PA was assessed with pedometers. The increase in mean steps after intervention in G2 was higher than the G1 and GC (P < 0.001). No differences between G1 and GC were observed at post-intervention (P = 0.05). The effects did not vary by gender or BMI. Providing game equipment and playground marks may increase children PA in recess. Nevertheless, additional PE-based intervention did not imply an improvement, and was not effective in increasing PA