1,569 research outputs found
Genomic and molecular landscape of DNA damage repair deficiency across The Cancer Genome Atlas
Characteristics of The Cancer Genome Atlas cases relative to U.S. general population cancer cases
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ISSLS PRIZE IN BIOENGINEERING SCIENCE 2019: biomechanical changes in dynamic sagittal balance and lower limb compensatory strategies following realignment surgery in adult spinal deformity patients.
Study designA longitudinal cohort study.ObjectiveTo define a set of objective biomechanical metrics that are representative of adult spinal deformity (ASD) post-surgical outcomes and that may forecast post-surgical mechanical complications. Current outcomes for ASD surgical planning and post-surgical assessment are limited to static radiographic alignment and patient-reported questionnaires. Little is known about the compensatory biomechanical strategies for stabilizing sagittal balance during functional movements in ASD patients.MethodsWe collected in-clinic motion data from 15 ASD patients and 10 controls during an unassisted sit-to-stand (STS) functional maneuver. Joint motions were measured using noninvasive 3D depth mapping sensor technology. Mathematical methods were used to attain high-fidelity joint-position tracking for biomechanical modeling. This approach provided reliable measurements for biomechanical behaviors at the spine, hip, and knee. These included peak sagittal vertical axis (SVA) over the course of the STS, as well as forces and muscular moments at various joints. We compared changes in dynamic sagittal balance (DSB) metrics between pre- and post-surgery and then separately compared pre- and post-surgical data to controls.ResultsStandard radiographic and patient-reported outcomes significantly improved following realignment surgery. From the DSB biomechanical metrics, peak SVA and biomechanical loads and muscular forces on the lower lumbar spine significantly reduced following surgery (- 19 to - 30%, all p < 0.05). In addition, as SVA improved, hip moments decreased (- 28 to - 65%, all p < 0.05) and knee moments increased (+ 7 to + 28%, p < 0.05), indicating changes in lower limb compensatory strategies. After surgery, DSB data approached values from the controls, with some post-surgical metrics becoming statistically equivalent to controls.ConclusionsLongitudinal changes in DSB following successful multi-level spinal realignment indicate reduced forces on the lower lumbar spine along with altered lower limb dynamics matching that of controls. Inadequate improvement in DSB may indicate increased risk of post-surgical mechanical failure. These slides can be retrieved under Electronic Supplementary Material
Subclinical infection of macaques and baboons with a baboon simarterivirus
Simarteriviruses (Arteriviridae: Simarterivirinae) are commonly found at high titers in the blood of African monkeys but do not cause overt disease in these hosts. In contrast, simarteriviruses cause severe disease in Asian macaques upon accidental or experimental transmission. Here, we sought to better understand the host-dependent drivers of simarterivirus pathogenesis by infecting olive baboons (n = 4) and rhesus monkeys (n = 4) with the simarterivirus Southwest baboon virus 1 (SWBV-1). Surprisingly, none of the animals in our study showed signs of disease following SWBV-1 inoculation. Three animals (two rhesus monkeys and one olive baboon) became infected and sustained high levels of SWBV-1 viremia for the duration of the study. The course of SWBV-1 infection was highly predictable: plasma viremia peaked between 1 × 107 and 1 × 108 vRNA copies/mL at 3–10 days post-inoculation, which was followed by a relative nadir and then establishment of a stable set-point between 1 × 106 and 1 × 107 vRNA copies/mL for the remainder of the study (56 days). We characterized cellular and antibody responses to SWBV-1 infection in these animals, demonstrating that macaques and baboons mount similar responses to SWBV-1 infection, yet these responses are ineffective at clearing SWBV-1 infection. SWBV-1 sequencing revealed the accumulation of non-synonymous mutations in a region of the genome that corresponds to an immunodominant epitope in the simarterivirus major envelope glycoprotein GP5, which likely contribute to viral persistence by enabling escape from host antibodies
Non-Chlamydial Bacterial Infection and Progression of Conjunctival Scarring in Trachoma.
Purpose: The purpose of this study was to assess whether non-chlamydial bacterial infection is associated with progression of trachomatous scarring in adults. Methods: This was a cohort study involving 800 participants in northern Tanzania who underwent clinical examination, photography, and conjunctival swab collection for microbiology over a 24-month period. Samples for microbiology were inoculated onto blood and chocolate agar, and Chlamydia trachomatis was detected by PCR. Progression was determined by comparison of baseline to 24-month photographs. Results: C. trachomatis was detected in only four participants at baseline. At 24 months, 617 participants (77.1%) were followed up. Of those seen at 24 months, 452 could be reliably assessed. Definite scarring progression (progressors) was seen in 345 (55.9%); there was no progression (nonprogressors) in 107 (17.3%). Using combined baseline and 12-month microbiology results, progressors had significantly higher levels of commensal and pathogenic bacterial organisms detected compared with nonprogressors. After adjusting for age, baseline scarring, and ethnicity, there was weak evidence (P = 0.07) that the bacteria category was associated with scarring progression (commensal organisms only: odds ratio [OR] = 1.61; 95% confidence interval [CI]: 0.90 to 2.89; pathogenic organisms either with or without commensal: OR = 2.39; 95% CI: 1.10 to 5.16). Conclusion: The findings were consistent with the possibility that trachomatous scarring in adults is associated with the presence of non-chlamydial bacterial organisms, particularly pathogenic organisms. C. trachomatis was detected very infrequently and may not be an important factor in the pathogenesis of scarring progression in adults. This has implications for trachoma control programs, which largely concentrate on reducing C. trachomatis levels and transmission
Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples
Publisher's version (útgefin grein)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.We acknowledge the contributions of the many clinical networks across ICGC and TCGA who provided samples and data to the PCAWG Consortium and the contributions of the Technical Working Group and the Germline Working Group of the PCAWG Consortium for collation, realignment, and harmonization of the variant calls of the cancer genomes used by this study. We thank the patients and their families for their participation in the individual ICGC and TCGA projects.Peer Reviewe
TB88: Descriptive and Comparative Studies of Maine Lakes
This is a descriptive and comparative study of 17 lakes in Maine. The major objectives of this study are (1) to characterize the pelagial zone of the lakes physically, chemically, and biologically, (2) to assess bacterial pollution, (3) to compare the lakes to each other and classify them trophically, and (4) to compare the lakes to others in different geographic regions.https://digitalcommons.library.umaine.edu/aes_techbulletin/1117/thumbnail.jp
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