947 research outputs found

    TReATS: a novel method for TAT-Cre recombinase mediated floxed Allele modification in ex vivo tissue slices

    Get PDF
    Precision-Cut Lung Slices (PCLS) are used for a variety of applications. However, methods to manipulate genes in PCLS are currently limited. We developed a novel method, TAT-Cre Recombinase-mediated floxed Allele modification in Tissue Slices (TReATS), to induce highly effective and temporally controlled gene deletion or activation in ex vivo PCLS. Treatment of PCLS from Rosa26-flox-stop-flox-EYFP mice with cell-permeant TAT-Cre recombinase induced ubiquitous EYFP protein expression, indicating successful Cre-mediated excision of the upstream loxP-flanked stop sequence. Quantitative real-time PCR confirmed induction of EYFP. We successfully replicated the TReATS method in PCLS from Vangl2flox/flox mice, leading to the deletion of loxP-flanked exon 4 of the Vangl2 gene. Cre-treated Vangl2flox/flox PCLS exhibited cytoskeletal abnormalities, a known phenotype caused by VANGL2 dysfunction. We report a novel method that by-passes conventional Cre-Lox breeding, allowing rapid and highly effective gene manipulation in ex vivo tissue models

    Crystal Distortion and the Two-Channel Kondo Effect

    Full text link
    We study a simple model of the two-channel Kondo effect in a distorted crystal. This model is then used to investigate the interplay of the Kondo and Jahn-Teller effects, and also the Kondo effect in an impure crystal. We find that the Jahn-Teller interaction modifies the characteristic energy scale of the system below which non-Fermi-liquid properties of the model become apparent. The modified energy scale tends to zero as the limit of a purely static Jahn-Teller effect is approached. We find also that the non-Fermi-liquid properties of the quadrupolar Kondo effect are not stable against crystal distortion caused by impurities.Comment: 11 page

    Nurse-led interventions among older adults affected by cancer: an integrative review.

    Get PDF
    Aging can introduce significant changes in health, cognition, function, social, and emotional status among older adults affected by cancer. Little is known about how existing nurse-led interventions address the needs of older adults. The objective was to identify existing nurse-led interventions among older adults to optimize recovery and survivorship needs. A integrative systematic review was reported conducted according to the PRISMA 2020 Guidelines. Electronic databases (APA PsycINFO, CINAHL, MEDLINE, Scopus, and Google Scholar databases) were searched using key search terms. Articles were assessed for inclusion according to a pre-determined eligibility criterion. Data extraction and quality appraisal were conducted. Findings were integrated in a narrative synthesis. 21 studies were included and a total of 4,253 participants represented. There were a range of study designs: quantitative (n=10), randomised controlled trials (n=6), mixed methods studies (n=3), qualitative (n=1) and a non-randomised controlled study (n=1). Most participants had prostate cancer with some representation in colorectal, lung, head and neck, renal, oesophageal, and mixed cancer patient populations. This review shows a lack of evidence on the inclusion of geriatric assessments for older people with cancer within existing nurse-led interventions. Further research is needed to test nurse-led interventions with the inclusion of geriatric assessments, and their contribution in the multidisciplinary team across the cancer care continuum for various cancer patient populations

    Characterization of Ferroplasma isolates and Ferroplasma acidarmanus sp nov., extreme acidophiles from acid mine drainage and industrial bioleaching environments

    Get PDF
    Three recently isolated extremely acidophilic archaeal strains have been shown to be phylogenetically similar to Ferroplasma acidiphilum Y-T by 16S rRNA gene sequencing. All four Ferroplasma isolates were capable of growing chemoorganotrophically on yeast extract or a range of sugars and chemomixotrophically on ferrous iron and yeast extract or sugars, and isolate "Ferroplasma acidarmanus" Fer1(T) required much higher levels of organic carbon. All four isolates were facultative anaerobes, coupling chemoorganotrophic growth on yeast extract to the reduction of ferric iron. The temperature optima for the four isolates were between 35 and 42degreesC and the pH optima were 1.0 to 1.7, and "F. acidarmanus" Fer1(T) was capable of growing at pH 0. The optimum yeast extract concentration for "F. acidarmanus" Fer1(T) was higher than that for the other three isolates. Phenotypic results suggested that isolate "F. acidarmanus" Fer1(T) is of a different species than the other three strains, and 16S rRNA sequence data, DNA-DNA similarity values, and two-dimensional polyacrylamide gel electrophoresis protein profiles clearly showed that strains DR1, MT17, and Y-T group as a single species. "F. acidarmanus" Fer1(T) groups separately, and we propose the new species "F. acidarmanus" Fer1(T) sp. nov

    Reporting issues in group sequential randomised controlled trials: a systematic review protocol of published journal reports

    Get PDF
    Background: Adaptive designs are somewhat underused, despite prominence given to methodology in the statistical literature. Some concerns relates to robustness of adaptive designs in decision making, acceptability of trial findings to change practice, anxiety about early stopping of trials and worry about wrong decision making. These issues could be linked to inadequate reporting of the conduct of such clinical trials. We assess the reporting of group sequential randomised controlled trials (RCTs), which are one of the most well-understood adaptive designs in the confirmatory setting. Methods: We undertake a systematic review searching Ovid MEDLINE from 1st January 2001 to 23rd September 2014 and including parallel group confirmatory group sequential RCTs that were prospectively designed using the Frequentist approach. Eligible trials are screened for completeness in reporting against the CONSORT 2010 checklist with some proposed modifications to capture issues such as statistical bias correction following early stopping. Descriptive statistics aided with forest plots on CONSORT compliance are presented. Discussion: Reporting of the conduct of adaptive designs is an area which has not been fully explored. Hence, the findings from this study can enlighten us on the adequacy in reporting of well-understood group sequential RCTs as a class of adaptive designs and on ways to address some of the cited concerns. Most importantly, the study can inform policy makers on the adequacy of the current CONSORT statements in enhancing reporting of such adaptive designs

    A rapid review indicated higher recruitment rates in treatment trials than in prevention trials

    Get PDF
    Objectives To test the hypothesis that the percentage of patients screened that randomize differs between prevention and therapy trials. Study Design and Setting Rapid review of randomized controlled trials (RCTs) identified through published systematic reviews in August 2013. Individually randomized, parallel group controlled RCTs were eligible if they evaluated metformin monotherapy or exercise for the prevention or treatment of type 2 diabetes. Numbers of patients screened and randomized were extracted by a single reviewer. Percentages were calculated for each study for those randomized: as a function of those approached, screened, and eligible. Percentages (95% confidence intervals) from each individual study were weighted according to the denominator and pooled rates calculated. Statistical heterogeneity was assessed using I2. Results The percentage of those screened who subsequently randomized was 6.2% (6.0%, 6.4%; 3 studies, I2 = 100.0%) for metformin prevention trials; 50.7% (49.9%, 51.4%; 21 studies, I2 = 99.6%) for metformin treatment trials; 4.8% (4.7%, 4.8%; 14 studies, I2 = 99.9%) for exercise prevention trials; and 43.3% (42.6%, 43.9%; 28 studies, I2 = 99.8%) for exercise treatment trials. Conclusion This study provides qualified support for the hypothesis that prevention trials recruit a smaller proportion of those screened than treatment trials. Statistical heterogeneity associated with pooled estimates and other study limitations is discussed. Keywords Prevention; Treatment; RCTs; Recruitment rates; Exercise; Screening failures; Consent rates; Eligibilit
    corecore