Impact of Age and HIV Status on Immune Activation, Senescence and Apoptosis

Introduction: Residual immune dysfunctions, resembling those that occur during normal aging, may persist even in well-treated people with HIV (PWH), and accelerated aging has been proposed. We aimed to determine if HIV infection is an independent risk factor for T-cell immune dysfunctions including increased immune activation, senescence and apoptosis. Moreover, in PWH we aimed to identify the associations between age and immune activation, senescence and apoptosis. Materials and Methods: We included 780 PWH with suppressed viral replication (<50 copies/mL) and absence of hepatitis B and hepatitis C co-infection and 65 uninfected controls from the Copenhagen Co-morbidity in HIV Infection (COCOMO) Study. Flow cytometry was used to determine T-cell activation (CD38+HLA-DR+), senescence (CD28-CD57+), and apoptosis (CD28-CD95+). T-cell subsets are reported as proportions of CD4+ and CD8+ T-cells. We defined an elevated proportion of a given T-cell subset as above the 75th percentile. Regression models were used to determine the association between HIV status and T-cell subset and in PWH to determine the association between age or HIV-specific risk factors and T-cell subsets. Furthermore, an interaction between HIV status and age on T-cell subsets was investigated with an interaction term in models including both PWH and controls. Models were adjusted for age, sex, BMI, and smoking status. Results: In adjusted models a positive HIV status was associated with elevated proportions of CD8+ activated (p = 0.009), CD4+ senescent (p = 0.004), CD4+ apoptotic (p = 0.002), and CD8+ apoptotic (p = 0.003) T-cells. In PWH a 10-year increase in age was associated with higher proportions of CD4+ and CD8+ senescent (p = 0.001 and p < 0.001) and CD4+ and CD8+ apoptotic T-cells (p < 0.001 and p < 0.001). However, no interaction between HIV status and age was found. Furthermore, in PWH a CD4+/CD8+ ratio < 1 was associated with elevated proportions of T-cell activation, senescence, and apoptosis. Discussion: We found evidence of residual T-cell immune dysfunction in well-treated PWH without HBV or HCV co-infection, and age was associated with T-cell senescence and apoptosis. Our data supports that HIV infection has similar effects as aging on T-cell subsets. However, since no interaction between HIV status and age was found on these parameters, we found no evidence to support accelerated immunological aging in PWH

Effectiveness and efficiency of primary care based case management for chronic diseases: rationale and design of a systematic review and meta-analysis of randomized and non-randomized trials [CRD32009100316]

Contains fulltext : 88751.pdf (publisher's version ) (Open Access)BACKGROUND: Case management is an important component of structured and evidence-based primary care for chronically ill patients. Its effectiveness and efficiency has been evaluated in numerous clinical trials. This protocol describes aims and methods of a systematic review of research on the effectiveness and efficiency of case management in primary care. METHODS/DESIGN: According to this protocol Medline, Embase, CINAHL, PsychInfo, the Cochrane Central Register of Controlled trials, DARE, NHS EED, Science Citation Index, The Royal College of Nursing Database, Dissertation Abstracts, registers of clinical trials and the reference lists of retrieved articles will be searched to identify reports on randomized and non-randomized controlled trials of case management interventions in a primary care setting without limitations on language or publication date. We will further ask experts in the field to avoid missing relevant evidence. Study inclusion and data extraction will be performed independently by two reviewers. After assessing risk of bias according to predefined standards, included studies will be described qualitatively. Subgroup analyses are planned for different chronic diseases and intervention strategies. If appropriate, a quantitative synthesis of data will be performed to provide conclusive evidence about the effectiveness and efficiency of primary care based case management in chronic care. REVIEW REGISTRATION: Centre for Reviews and Dissemination (University of York): CRD32009100316

Effectiveness of early intervention programs for parents of preterm infants: a meta-review of systematic reviews

Background: Various intervention programs exist for parents of preterm babies and some systematic reviews (SRs) have synthesised the evidence of their effectiveness. These reviews are, however, limited to specific interventions, components, or outcomes, and a comprehensive evidence base is lacking. The aim of this meta-review was to appraise and meta-synthesise the evidence from existing SRs to provide a comprehensive evidence base on the effectiveness of interventions for parents of preterm infants on parental and infant outcomes. Methods: We conducted a comprehensive search of the following databases to identify relevant SRs: Cochrane library, Web of science, EMBASE, CINAHL, British Nursing Index, PsycINFO, Medline, ScienceDirect, Scopus, IBSS, DOAJ, ERIC, EPPI-Centre, PROSPERO, WHO Library. Additional searches were conducted using authors’ institutional libraries, Google Scholar, and the reference lists of identified reviews. Identified articles were screened in two stages against an inclusion criteria with titles and abstracts screened first followed by full-text screening. Selected SRs were appraised using the AMSTAR tool. Extracted data using a predesigned tool were synthesised narratively examining the direction of impact on outcomes. Results: We found 11 SRs eligible for inclusion that synthesised a total of 343 quantitative primary studies. The average quality of the SRs was ‘medium’. Thirty four interventions were reported across the SRs with considerable heterogeneity in the structural framework and the targeted outcomes that included maternal-infant dyadic, maternal/parental, and infant outcomes. Among all interventions, Kangaroo Care (KC) showed the most frequent positive impact across outcomes (n = 19) followed by Mother Infant Transaction Program (MITP) (n = 14). Other interventions with most consistent positive impact on infant outcomes were Modified-Mother Infant Transaction Program (M-MITP) (n = 6), Infant Health and Development Program (IHDP) (n = 5) and Creating Opportunities for Parent Empowerment (COPE) (n = 5). Overall, interventions with both home and facility based components showed the most frequent positive impact across outcomes. Conclusions: Neonatal care policy and planning for preterm babies should consider the implementation of interventions with most positive impact on outcomes. The heterogeneity in interventions and outcomes calls for the development and implementation of an integrated program for parents of preterm infants with a clearly defined global set of parental and infant outcomes

Data-Driven Artificial Intelligence for Calibration of Hyperspectral Big Data

Near-earth hyperspectral big data present both huge opportunities and challenges for spurring developments in agriculture and high-throughput plant phenotyping and breeding. In this article, we present data-driven approaches to address the calibration challenges for utilizing near-earth hyperspectral data for agriculture. A data-driven, fully automated calibration workflow that includes a suite of robust algorithms for radiometric calibration, bidirectional reflectance distribution function (BRDF) correction and reflectance normalization, soil and shadow masking, and image quality assessments was developed. An empirical method that utilizes predetermined models between camera photon counts (digital numbers) and downwelling irradiance measurements for each spectral band was established to perform radiometric calibration. A kernel-driven semiempirical BRDF correction method based on the Ross Thick-Li Sparse (RTLS) model was used to normalize the data for both changes in solar elevation and sensor view angle differences attributed to pixel location within the field of view. Following rigorous radiometric and BRDF corrections, novel rule-based methods were developed to conduct automatic soil removal; and a newly proposed approach was used for image quality assessment; additionally, shadow masking and plot-level feature extraction were carried out. Our results show that the automated calibration, processing, storage, and analysis pipeline developed in this work can effectively handle massive amounts of hyperspectral data and address the urgent challenges related to the production of sustainable bioenergy and food crops, targeting methods to accelerate plant breeding for improving yield and biomass traits

Respiratory syncytial virus: diagnosis, prevention and management.

Respiratory syncytial virus (RSV) is responsible for a large burden of disease globally and can present as a variety of clinical syndromes in children of all ages. Bronchiolitis in infants under 1 year of age is the most common clinical presentation hospitalizing 24.2 per 1000 infants each year in the United Kingdom. RSV has been shown to account for 22% of all episodes of acute lower respiratory tract infection in children globally. RSV hospitalization, that is, RSV severe disease, has also been associated with subsequent chronic respiratory morbidity. Routine viral testing in all children is not currently recommended by the United Kingdom National Institute for Health and Care Excellence (NICE) or the American Academy of Pediatrics (AAP) guidance and management is largely supportive. There is some evidence for the use of ribavirin in severely immunocompromised children. Emphasis is placed on prevention of RSV infection through infection control measures both in hospital and in the community, and the use of the RSV-specific monoclonal antibody, palivizumab, for certain high-risk groups of infants. New RSV antivirals and vaccines are currently in development. Ongoing work is needed to improve the prevention of RSV infection, not only because of the acute morbidity and mortality, but also to reduce the associated chronic respiratory morbidity after severe infection

Oral rehydration versus intravenous therapy for treating dehydration due to gastroenteritis in children: a meta-analysis of randomised controlled trials

BACKGROUND: Despite treatment recommendations from various organizations, oral rehydration therapy (ORT) continues to be underused, particularly by physicians in high-income countries. We conducted a systematic review of randomised controlled trials (RCTs) to compare ORT and intravenous therapy (IVT) for the treatment of dehydration secondary to acute gastroenteritis in children. METHODS: RCTs were identified through MEDLINE, EMBASE, CENTRAL, authors and references of included trials, pharmaceutical companies, and relevant organizations. Screening and inclusion were performed independently by two reviewers in order to identify randomised or quasi-randomised controlled trials comparing ORT and IVT in children with acute diarrhea and dehydration. Two reviewers independently assessed study quality using the Jadad scale and allocation concealment. Data were extracted by one reviewer and checked by a second. The primary outcome measure was failure of rehydration. We analyzed data using standard meta-analytic techniques. RESULTS: The quality of the 14 included trials ranged from 0 to 3 (Jadad score); allocation concealment was unclear in all but one study. Using a random effects model, there was no significant difference in treatment failures (risk difference [RD] 3%; 95% confidence intervals [CI]: 0, 6). The Mantel-Haenzsel fixed effects model gave a significant difference between treatment groups (RD 4%; 95% CI: 2, 5) favoring IVT. Based on the four studies that reported deaths, there were six in the IVT groups and two in ORT. There were no significant differences in total fluid intake at six and 24 hours, weight gain, duration of diarrhea, or hypo/hypernatremia. Length of stay was significantly shorter for the ORT group (weighted mean difference [WMD] -1.2 days; 95% CI: -2.4,-0.02). Phlebitis occurred significantly more often with IVT (number needed to treat [NNT] 33; 95% CI: 25,100); paralytic ileus occurred more often with ORT (NNT 33; 95% CI: 20,100). These results may not be generalizable to children with persistent vomiting. CONCLUSION: There were no clinically important differences between ORT and IVT in terms of efficacy and safety. For every 25 children (95% CI: 20, 50) treated with ORT, one would fail and require IVT. The results support existing practice guidelines recommending ORT as the first course of treatment in appropriate children with dehydration secondary to gastroenteritis

Racemic epinephrine compared to salbutamol in hospitalized young children with bronchiolitis; a randomized controlled clinical trial [ISRCTN46561076]

BACKGROUND: Bronchiolitis is the most common cause of lower respiratory tract illness in infancy, and hospital admission rates appear to be increasing in Canada and the United States. Inhaled beta agonists offer only modest short-term improvement. Trials of racemic epinephrine have shown conflicting results. We sought to determine if administration of racemic epinephrine during hospital stay for bronchiolitis improved respiratory distress, was safe, and shortened length of stay. METHODS: The study was a randomized, double-blind controlled trial of aerosolized racemic epinephrine compared to salbutamol every one to 4 hours in previously well children aged 6 weeks to ≤ 2 years of age hospitalized with bronchiolitis. The primary outcome was symptom improvement as measured by the Respiratory Distress Assessment Instrument (RDAI); secondary outcomes were length of stay in hospital, adverse events, and report of symptoms by structured parental telephone interview one week after discharge. RESULTS: 62 children with a mean age of 6.4 months were enrolled; 80% of children had Respiratory Syncytial Virus (RSV). Racemic epinephrine resulted in significant improvement in wheezing and the total RDAI score on day 2 and over the entire stay (p < 0.05). The mean LOS in the epinephrine arm was 2.6 days (95% CI 2, 3.2) v. 3.4 days in those in the salbutamol group (95% CI 2.6, 4.2) (p > 0.05). Adverse events were not significantly different in the two arms. At one week post-discharge, over half of parents reported that their child still had a respiratory symptom and 40% had less than normal feeding. CONCLUSION: Racemic epinephrine relieves respiratory distress in hospitalized infants with bronchiolitis and is safe but does not abbreviate hospital stay. Morbidity associated with bronchiolitis as identified by parents persists for at least one week after hospital discharge in most infants

Relative efficacy of topical non-steroidal anti-inflammatory drugs and topical capsaicin in osteoarthritis: protocol for an individual patient data meta-analysis

Background Pain is the most troubling issue to patients with osteoarthritis (OA), yet current pharmacological treatments offer only small-to-moderate pain reduction. Current guidelines therefore emphasise the need to identify predictors of treatment response. In line with these recommendations, an individual patient data (IPD) meta-analysis will be conducted. The study aims to investigate the relative treatment effects of topical non-steroidal anti-inflammatory drugs (NSAIDs) and topical capsaicin in OA and to identify patient-level predictors of treatment response. Methods IPD will be collected from randomised controlled trials (RCTs) of topical NSAIDs and capsaicin in OA. Multilevel regression modelling will be conducted to determine predictors for the specific and the overall treatment effect. Discussion Through the identification of treatment responders, this IPD meta-analysis may improve the current understanding of the pain mechanisms in OA and guide clinical decision-making. Identifying and prescribing the treatment most likely to be beneficial for an individual with OA will improve the efficiency of patient management

High-Throughput Top-Down Fabrication of Uniform Magnetic Particles

Ion Beam Aperture Array Lithography was applied to top-down fabrication of large dense (108–109 particles/cm2) arrays of uniform micron-scale particles at rates hundreds of times faster than electron beam lithography. In this process, a large array of helium ion beamlets is formed when a stencil mask containing an array of circular openings is illuminated by a broad beam of energetic (5–8 keV) ions, and is used to write arrays of specific repetitive patterns. A commercial 5-micrometer metal mesh was used as a stencil mask; the mesh size was adjusted by shrinking the stencil openings using conformal sputter-deposition of copper. Thermal evaporation from multiple sources was utilized to form magnetic particles of varied size and thickness, including alternating layers of gold and permalloy. Evaporation of permalloy layers in the presence of a magnetic field allowed creation of particles with uniform magnetic properties and pre-determined magnetization direction. The magnetic properties of the resulting particles were characterized by Vibrating Sample Magnetometry. Since the orientation of the particles on the substrate before release into suspension is known, the orientation-dependent magnetic properties of the particles could be determined