The influence of gap size on the development of fracture union with a micro external fixator

Increasingly, the rat femoral fracture model is being used for preclinical investigations of fracture healing, however, the effect of gap size and its influence on mechanobiology is not well understood. We aimed to evaluate the influence of osteotomy gap on osteotomy healing between the previously published extremes of guaranteed union (0.5 mm) and non-union (3 mm) using this model. A femoral osteotomy in 12–14 week old female Wistar rats was stabilised with a micro fixator (titanium blocks, carbon fiber bars) with an osteotomy gap of 1.0 mm (n = 5), 1.5 mm (n = 7), 2.0 mm (n = 6). After five weeks, the left femur was retrieved. The osteotomy gap was scanned using X-ray microtomography and then histologically evaluated. The radiographic union rate (complete mineralised bone bridging across the osteotomy) was three times higher for the 1.0 mm than the 2.0 mm gap. The 1.0 mm gap had the largest callus (0.069μm3) and bone volume (0.035μm3). Callus and bone volume were approximately 50% smaller within the 2.0 mm gap. Using cadaveric rat femurs stabilised with the external fixator, day 0 mechanical assessment of construct stiffness was calculated on materials testing machine displacement vs load output. The construct stiffness for the 1.0, 1.5 and 2.0 mm gaps was 32.6 ± 5.4, 32.5 ± 2.4, and 32.4 ± 8.3 N/mm (p = 0.779). Interfragmentary strain (IFS) was calculated using the change in osteotomy gap displacement as measured using microstrain miniature differential reluctance transducer spanning the osteotomy gap. Increasing the gap size significantly reduced the IFS (p = 0.013). The mean ‘day 0’ IFS for the 1.0, 1.5 and 2.0 mm gaps were 11.2 ± 1.3, 8.4 ± 1.5 and 6.1 ± 1.2% respectively. A 1.5 mm gap resulted in a delayed fracture healing by 5 weeks and may represent a useful test environment for fracture healing therapy. Increasing gap size did not affect construct stiffness, but did reduce the ‘day 0’ IFS, with a doubling of non-union and halving of bone volume measured between 1.0 and 2.0 mm gaps

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Obituaries: Ro - Ry Folder

103 pages of subject files containing and related to Obituaries: Ro - R

Immune activation in HIV-infected aging women on antiretrovirals--implications for age-associated comorbidities: a cross-sectional pilot study.

Persistent immune activation and microbial translocation associated with HIV infection likely place HIV-infected aging women at high risk of developing chronic age-related diseases. We investigated immune activation and microbial translocation in HIV-infected aging women in the post-menopausal ages.Twenty-seven post-menopausal women with HIV infection receiving antiretroviral treatment with documented viral suppression and 15 HIV-negative age-matched controls were enrolled. Levels of immune activation markers (T cell immune phenotype, sCD25, sCD14, sCD163), microbial translocation (LPS) and biomarkers of cardiovascular disease and impaired cognitive function (sVCAM-1, sICAM-1 and CXCL10) were evaluated.T cell activation and exhaustion, monocyte/macrophage activation, and microbial translocation were significantly higher in HIV-infected women when compared to uninfected controls. Microbial translocation correlated with T cell and monocyte/macrophage activation. Biomarkers of cardiovascular disease and impaired cognition were elevated in women with HIV infection and correlated with immune activation.HIV-infected antiretroviral-treated aging women who achieved viral suppression are in a generalized status of immune activation and therefore are at an increased risk of age-associated end-organ diseases compared to uninfected age-matched controls

A provisional tool for the measurement of sleep satisfaction

Objectives The goal of this project was to provisionally identify the basic elements of sleep satisfaction within the general population. Methods The National Sleep Foundation conducted a systematic literature review and identified 495 published articles evaluating potential indicators of sleep satisfaction. The National Sleep Foundation then convened an expert panel (\ue2\u80\u9cPanel\ue2\u80\u9d), provided full-text articles and summaries, and used a modified RAND appropriateness method with three total rounds of voting to determine the appropriateness of indicators for sleep satisfaction. Results The literature review revealed no tools or measures of sleep satisfaction (not dissatisfaction) applied to the general population and directly associated with good health. Nonetheless, a variety of sleep factors were extracted from the extant sleep research literature. Panel members voted on these indicators: sleep environmental factors; and sleep initiation and maintenance parameters. Using these indicators, the Panel constructed provisional questions for measuring sleep satisfaction. Conclusions The Panel determined that appropriate sleep satisfaction elements include how an individual feels (a) about their sleep, (b) immediately after their sleep, and (c) during the subsequent day. Additionally, appropriate environmental elements include (a) bedding comfort, (b) bedroom temperature, and (c) noise and light in the bedroom. How one feels with (a) the time it takes to fall asleep, (b) the ease with which one falls back to sleep after awakening during a sleep period, (c) the amount of sleep on weekdays and weekends, as well as how undisturbed one's sleep is also were determined to be appropriate contributors to sleep satisfaction. Finally, the Panel agreed that whether an individual desired to change anything about their sleep, is a relevant question

Biomarkers of cardiovascular disease and impaired neurocognition are increased in HIV-infected post-menopausal women.

<p>Levels of sVCAM-1, sICAM-1 and CXCL10 were measured by ELISA in the plasma of 15 HIV– and 26 HIV+ women. Comparisons between the two groups were performed using Student <i>t</i>-test. Significant P values are shown in bold.</p