378 research outputs found

    microRNA expression in the aging mouse lung

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    BACKGROUND: MicroRNAs (miRNAs) are a novel class of short double stranded RNA that mediate the post-transcriptional regulation of gene expression. Previous studies have implicated changes in miRNA expression in the regulation of development and the induction of diseases such as cancer. However, although miRNAs have been implicated in the process of aging in C. elegans, nothing is known of their role in mammalian tissues. RESULTS: To address this question, we have used a highly-sensitive, semi-quantitative RT-PCR based approach to measure the expression profile of 256 of the 493 currently identified miRNAs in the lungs from 6 month (adult) and 18 month (aged) old female BALB/c mice. We show that, despite the characteristic changes in anatomy and gene expression associated with lung aging, there were no significant changes in the expression of 256 miRNAs. CONCLUSION: Overall, these results show that miRNA transcription is unchanged during lung aging and suggests that stable expression of miRNAs might instead buffer age related changes in the expression of protein-encoding gene

    Perturbation of a turbulent boundary layer by spatially-impulsive dynamic roughness

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    First experimental measurements of manipulation of the structure of a canonical zero pressure gradient turbulent boundary layer using a low frequency (compared to the viscous frequency) mechanical dynamic roughness are presented. “Dynamic” (or time-dependent) surface roughness is proposed as a method for both control and diagnosis of turbulent boundary layers

    Non-Abelian Magnetized Blackholes and Unstable Attractors

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    Fluctuations of non-Abelian gauge fields in a background magnetic flux contain tachyonic modes and hence the background is unstable. We extend these results to the cases where the background flux is coupled to Einstein gravity and show that the corresponding spherically symmetric geometries, which in the absence of a cosmological constant are of the form of Reissner-Nordstrom blackholes or the AdS_2xS^2, are also unstable. We discuss the relevance of these instabilities to several places in string theory including various string compactifications and the attractor mechanism. Our results for the latter imply that the attractor mechanism shown to work for the extremal Abelian charged blackholes, cannot be applied in a straightforward way to the extremal non-Abelian colored blackholes.Comment: 23 pages, 3 .eps figures; v2: Stability of minimal charge blackhole emphasized, Refs adde

    Palaeoproterozoic magnesite: lithological and isotopic evidence for playa/sabkha environments

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    Magnesite forms a series of 1- to 15-m-thick beds within the approximate to2.0 Ga (Palaeoproterozoic) Tulomozerskaya Formation, NW Fennoscandian Shield, Russia. Drillcore material together with natural exposures reveal that the 680-m-thick formation is composed of a stromatolite-dolomite-'red bed' sequence formed in a complex combination of shallow-marine and non-marine, evaporitic environments. Dolomite-collapse breccia, stromatolitic and micritic dolostones and sparry allochemical dolostones are the principal rocks hosting the magnesite beds. All dolomite lithologies are marked by delta C-13 values from +7.1 parts per thousand to +11.6 parts per thousand (V-PDB) and delta O-18 ranging from 17.4 parts per thousand to 26.3 parts per thousand (V-SMOW). Magnesite occurs in different forms: finely laminated micritic; stromatolitic magnesite; and structureless micritic, crystalline and coarsely crystalline magnesite. All varieties exhibit anomalously high delta C-13 values ranging from +9.0 parts per thousand to +11.6 parts per thousand and delta O-18 values of 20.0-25.7 parts per thousand. Laminated and structureless micritic magnesite forms as a secondary phase replacing dolomite during early diagenesis, and replaced dolomite before the major phase of burial. Crystalline and coarsely crystalline magnesite replacing micritic magnesite formed late in the diagenetic/metamorphic history. Magnesite apparently precipitated from sea water-derived brine, diluted by meteoric fluids. Magnesitization was accomplished under evaporitic conditions (sabkha to playa lake environment) proposed to be similar to the Coorong or Lake Walyungup coastal playa magnesite. Magnesite and host dolostones formed in evaporative and partly restricted environments; consequently, extremely high delta C-13 values reflect a combined contribution from both global and local carbon reservoirs. A C- 13-rich global carbon reservoir (delta C-13 at around +5 parts per thousand) is related to the perturbation of the carbon cycle at 2.0 Ga, whereas the local enhancement in C-13 (up to +12 parts per thousand) is associated with evaporative and restricted environments with high bioproductivity

    Interventions for female drug-using offenders

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    Background This review represents one in a family of three reviews focusing on the effectiveness of interventions in reducing drug use and criminal activity for offenders. Objectives To assess the effectiveness of interventions for female drug‐using offenders in reducing criminal activity, or drug use, or both. Search methods We searched 12 electronic bibliographic databases up to February 2019. Selection criteria We included randomised controlled trials (RCTs). Data collection and analysis We used standard methodological procedures expected by Cochrane. Main results We included 13 trials with 2560 participants. Interventions were delivered in prison (7/13 studies, 53%) and community (6/13 studies, 47%) settings. The rating of bias was affected by the lack of clear reporting by authors, and we rated many items as 'unclear'. In two studies (190 participants) collaborative case management in comparison to treatment as usual did not reduce drug use (risk ratio (RR) 0.65, 95% confidence interval (CI) 0.20 to 2.12; 1 study, 77 participants; low‐certainty evidence), reincarceration at nine months (RR 0.71, 95% CI 0.32 to 1.57; 1 study, 77 participants; low‐certainty evidence), and number of subsequent arrests at 12 months (RR 1.11, 95% CI 0.83 to 1.49; 1 study, 113 participants; low‐certainty evidence). One study (36 participants) comparing buprenorphine to placebo showed no significant reduction in self‐reported drug use at end of treatment (RR 0.57, 95% CI 0.27 to 1.20) and three months (RR 0.58, 95% CI 0.25 to 1.35); very low‐certainty evidence. No adverse events were reported. One study (38 participants) comparing interpersonal psychotherapy to a psychoeducational intervention did not find reduction in drug use at three months (RR 0.67, 95% CI 0.30 to 1.50; low‐certainty evidence). One study (31 participants) comparing acceptance and commitment therapy (ACT) to a waiting list showed no significant reduction in self‐reported drug use using the Addiction Severity Index (mean difference (MD) ‐0.04, 95% CI ‐0.37 to 0.29) and abstinence from drug use at six months (RR 2.89, 95% CI 0.73 to 11.43); low‐certainty evidence. One study (314 participants) comparing cognitive behavioural skills to a therapeutic community programme and aftercare showed no significant reduction in self‐reported drug use (RR 0.86, 95% CI 0.58 to 1.27), re‐arrest for any type of crime (RR 0.73, 95% CI 0.52 to 1.03); criminal activity (RR 0.80, 95% CI 0.63 to 1.03), or drug‐related crime (RR 0.95, 95% CI 0.68 to 1.32). A significant reduction for arrested (not for parole) violations at six months follow‐up was significantly in favour of cognitive behavioural skills (RR 0.43, 95% CI 0.25 to 0.77; very low‐certainty evidence). A second study with 115 participants comparing cognitive behavioural skills to an alternative substance abuse treatment showed no significant reduction in reincarceration at 12 months (RR 0.70, 95% CI 0.43 to 1.12; low certainty‐evidence. One study (44 participants) comparing cognitive behavioural skills and standard therapy versus treatment as usual showed no significant reduction in Addiction Severity Index (ASI) drug score at three months (MD 0.02, 95% CI ‐0.05 to 0.09) and six months (MD ‐0.02, 95% CI ‐0.09 to 0.05), and incarceration at three months (RR 0.46, 95% CI 0.04 to 4.68) and six months (RR 0.51, 95% CI 0.20 to 1.27); very low‐certainty evidence. One study (171 participants) comparing a single computerised intervention versus case management showed no significant reduction in the number of days not using drugs at three months (MD ‐0.89, 95% CI ‐4.83 to 3.05; low certainty‐evidence). One study (116 participants) comparing dialectic behavioural therapy and case management (DBT‐CM) versus a health promotion intervention showed no significant reduction at six months follow‐up in positive drug testing (RR 0.67, 95% CI 0.43 to 1.03), number of people not using marijuana (RR 1.23, 95% CI 0.95 to 1.59), crack (RR 1.00, 95% CI 0.87 to 1.14), cocaine (RR 1.02, 95% CI 0.93 to 1.12), heroin (RR 1.05, 95% CI 0.98 to 1.13), methamphetamine (RR 1.02, 95% CI 0.87 to 1.20), and self‐reported drug use for any drug (RR 1.20, 95% CI 0.92 to 1.56); very low‐certainty evidence. One study (211 participants) comparing a therapeutic community programme versus work release showed no significant reduction in marijuana use at six months (RR 1.03, 95% CI 0.19 to 5.65), nor 18 months (RR 1.00, 95% CI 0.07 to 14.45), heroin use at six months (RR 1.59, 95% CI 0.49 to 5.14), nor 18 months (RR 1.92, 95% CI 0.24 to 15.37), crack use at six months (RR 2.07, 95% CI 0.41 to 10.41), nor 18 months (RR 1.64, 95% CI 0.19 to 14.06), cocaine use at six months (RR 1.09, 95% CI 0.79 to 1.50), nor 18 months (RR 0.93, 95% CI 0.64 to 1.35). It also showed no significant reduction in incarceration for drug offences at 18 months (RR 1.45, 95% CI 0.87 to 2.42); with overall very low‐ to low‐certainty evidence. One study (511 participants) comparing intensive discharge planning and case management versus prison only showed no significant reduction in use of marijuana (RR 0.79, 95% CI 0.53 to 1.16), hard drugs (RR 1.12, 95% CI 0.88 to 1.43), crack cocaine (RR 1.08, 95% CI 0.75 to 1.54), nor positive hair testing for marijuana (RR 0.75, 95% CI 0.55 to 1.03); it found a significant reduction in arrests (RR 0.19, 95% CI 0.04 to 0.87), but no significant reduction in drug charges (RR 1.07, 95% CI 0.75 to 1.53) nor incarceration (RR 1.09, 95% CI 0.86 to 1.39); moderate‐certainty evidence. One narrative study summary (211 participants) comparing buprenorphine pre‐ and post‐release from prison showed no significant reduction in drug use at 12 months post‐release; low certainty‐evidence. No adverse effects were reported. Authors' conclusions The studies showed a high degree of heterogeneity for types of comparisons, outcome measures and small samples. Descriptions of treatment modalities are required. On one outcome of arrest (no parole violations), we identified a significant reduction when cognitive behavioural therapy (CBT) was compared to a therapeutic community programme. But for all other outcomes, none of the interventions were effective. Larger trials are required to increase the precision of confidence about the certainty of evidence

    Recreational Physical Activity and Risk of Incident Knee Osteoarthritis: An International Meta-Analysis of Individual Participant–Level Data

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    Objective: The effect of physical activity on the risk of developing knee osteoarthritis (OA) is unclear. We undertook this study to examine the relationship between recreational physical activity and incident knee OA outcomes using comparable physical activity and OA definitions. Methods: Data were acquired from 6 global, community-based cohorts of participants with and those without knee OA. Eligible participants had no evidence of knee OA or rheumatoid arthritis at baseline. Participants were followed up for 5–12 years for incident outcomes including the following: 1) radiographic knee OA (Kellgren-Lawrence [K/L] grade ≥2), 2) painful radiographic knee OA (radiographic OA with knee pain), and 3) OA-related knee pain. Self-reported recreational physical activity included sports and walking/cycling activities and was quantified at baseline as metabolic equivalents of task (METs) in days per week. Risk ratios (RRs) were calculated and pooled using individual participant data meta-analysis. Secondary analysis assessed the association between physical activity, defined as time (hours per week) spent in recreational physical activity and incident knee OA outcomes. Results: Based on a total of 5,065 participants, pooled RR estimates for the association of MET days per week with painful radiographic OA (RR 1.02 [95% confidence interval (95% CI) 0.93–1.12]), radiographic OA (RR 1.00 [95% CI 0.94–1.07]), and OA-related knee pain (RR 1.00 [95% CI 0.96–1.04]) were not significant. Similarly, the analysis of hours per week spent in physical activity also showed no significant associations with all outcomes. Conclusion: Our findings suggest that whole-body, physiologic energy expenditure during recreational activities and time spent in physical activity were not associated with incident knee OA outcomes

    Psychosocial Treatment of Children in Foster Care: A Review

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    A substantial number of children in foster care exhibit psychiatric difficulties. Recent epidemiologi-cal and historical trends in foster care, clinical findings about the adjustment of children in foster care, and adult outcomes are reviewed, followed by a description of current approaches to treatment and extant empirical support. Available interventions for these children can be categorized as either symptom-focused or systemic, with empirical support for specific methods ranging from scant to substantial. Even with treatment, behavioral and emotional problems often persist into adulthood, resulting in poor functional outcomes. We suggest that self-regulation may be an important mediat-ing factor in the appearance of emotional and behavioral disturbance in these children

    Estimating the current and future cancer burden in Canada: Methodological framework of the Canadian population attributable risk of cancer (ComPARe) study

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    Introduction The Canadian Population Attributable Risk of Cancer project aims to quantify the number and proportion of cancer cases incident in Canada, now and projected to 2042, that could be prevented through changes in the prevalence of modifiable exposures associated with cancer. The broad risk factor categories of interest include tobacco, diet, energy imbalance, infectious diseases, hormonal therapies and environmental factors such as air pollution and res

    Bio-analytical Assay Methods used in Therapeutic Drug Monitoring of Antiretroviral Drugs-A Review

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