517 research outputs found

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    The progressive supper Aubrey Waddy; Felixstowe, England; 2003; Rhapsody; 254 pages; £10.5

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    Potential problems with industry-supported clinical research

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    Movement of Walleyes in Lakes Erie and St. Clair Inferred from Tag Return and Fisheries Data

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    Lake Erie walleyes Sander vitreus support important fisheries and have been managed as one stock, although preliminary tag return and genetic analyses suggest the presence of multiple stocks that migrate among basins within Lake Erie and into other portions of the Great Lakes. We examined temporal and spatial movement and abundance patterns of walleye stocks in the three basins of Lake Erie and in Lake St. Clair with the use of tag return and sport and commercial catchâ perâ unit effort (CPUE) data from 1990 to 2001. Based on summer tag returns, western basin walleyes migrated to the central and eastern basins of Lake Erie and to Lake St. Clair and southern Lake Huron, while fish in the central and eastern basins of Lake Erie and in Lake St. Clair were primarily caught within the basins where they were tagged. Seasonal changes in sport and commercial effort and CPUE in Lake Erie confirmed the walleye movements suggested by tag return data. Walleyes tagged in the western basin but recaptured in the central or eastern basin of Lake Erie were generally larger (or older) than those recaptured in the western basin of Lake Erie or in Lake St. Clair. Within spawning stocks, female walleyes had wider ranges of movement than males and there was considerable variation in movement direction, minimum distance moved (mean distance between tagging sites and recapture locations), and mean length among individual spawning stocks. Summer temperatures in the western basin often exceeded the optimal temperature (20â 23°C) for growth of large walleyes, and the migration of western basin walleyes might represent a sizeâ dependent response to warm summer temperatures. Cooler temperatures and abundant softâ rayed fish probably contributed to an energetically favorable foraging habitat in the central and eastern basins that attracted large walleyes during summer.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141620/1/tafs0539.pd

    Pragmatism over principle: US intervention and burden shifting in Somalia, 1992–1993

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    The conventional wisdom about the 1992 US intervention in Somalia is that it was a quintessentially humanitarian mission pushed by President George H. W. Bush. This article challenges that interpretation, drawing on newly declassified documents. The Somalia intervention, I argue, was largely a pragmatic response to concerns held by the US military. In late 1992, as the small UN mission in Somalia was collapsing, senior American generals worried about being drawn into the resulting vacuum. Hence they reluctantly recommended a robust US intervention, in the expectation that this would allow the UN to assemble a larger peacekeeping force that would take over within months. The intervention ultimately failed, but the military learned useful lessons from this experience on how to achieve smoother UN handoffs in the future and thus effectively shift longer-term stabilisation burdens to the international community.Open access publication was made possible by an EC Career Integration Grant

    Early Detection of Ovarian Cancer using the Risk of Ovarian Cancer Algorithm with Frequent CA125 Testing in Women at Increased Familial Risk – Combined Results from Two Screening Trials

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    Purpose: Women at familial/genetic ovarian cancer risk often undergo screening despite unproven efficacy. Research suggests each woman has her own CA125 baseline; significant increases above this level may identify cancers earlier than standard 6- to 12-monthly CA125 > 35 U/mL. Experimental Design: Data from prospective Cancer Genetics Network and Gynecologic Oncology Group trials, which screened 3,692 women (13,080 woman-screening years) with a strong breast/ovarian cancer family history or BRCA1/2 mutations, were combined to assess a novel screening strategy. Specifically, serum CA125 q3 months, evaluated using a risk of ovarian cancer algorithm (ROCA), detected significant increases above each subject's baseline, which triggered transvaginal ultrasound. Specificity and positive predictive value (PPV) were compared with levels derived from general population screening (specificity 90%, PPV 10%), and stage-at-detection was compared with historical high-risk controls. Results: Specificity for ultrasound referral was 92% versus 90% ( P = 0.0001), and PPV was 4.6% versus 10% ( P > 0.10). Eighteen of 19 malignant ovarian neoplasms [prevalent = 4, incident = 6, risk-reducing salpingo-oophorectomy (RRSO) = 9] were detected via screening or RRSO. Among incident cases (which best reflect long-term screening performance), three of six invasive cancers were early-stage (I/II; 50% vs. 10% historical BRCA1 controls; P = 0.016). Six of nine RRSO-related cases were stage I. ROCA flagged three of six (50%) incident cases before CA125 exceeded 35 U/mL. Eight of nine patients with stages 0/I/II ovarian cancer were alive at last follow-up (median 6 years). Conclusions: For screened women at familial/genetic ovarian cancer risk, ROCA q3 months had better early-stage sensitivity at high specificity, and low yet possibly acceptable PPV compared with CA125 > 35 U/mL q6/q12 months, warranting further larger cohort evaluation. Clin Cancer Res; 23(14); 3628-37. ©2017 AACR

    Immunological modifications following chemotherapy are associated with delayed recurrence of ovarian cancer

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    IntroductionOvarian cancer recurs in most High Grade Serous Ovarian Cancer (HGSOC) patients, including initial responders, after standard of care. To improve patient survival, we need to identify and understand the factors contributing to early or late recurrence and therapeutically target these mechanisms. We hypothesized that in HGSOC, the response to chemotherapy is associated with a specific gene expression signature determined by the tumor microenvironment. In this study, we sought to determine the differences in gene expression and the tumor immune microenvironment between patients who show early recurrence (within 6 months) compared to those who show late recurrence following chemotherapy.MethodsPaired tumor samples were obtained before and after Carboplatin and Taxol chemotherapy from 24 patients with HGSOC. Bioinformatic transcriptomic analysis was performed on the tumor samples to determine the gene expression signature associated with differences in recurrence pattern. Gene Ontology and Pathway analysis was performed using AdvaitaBio’s iPathwayGuide software. Tumor immune cell fractions were imputed using CIBERSORTx. Results were compared between late recurrence and early recurrence patients, and between paired pre-chemotherapy and post-chemotherapy samples.ResultsThere was no statistically significant difference between early recurrence or late recurrence ovarian tumors pre-chemotherapy. However, chemotherapy induced significant immunological changes in tumors from late recurrence patients but had no impact on tumors from early recurrence patients. The key immunological change induced by chemotherapy in late recurrence patients was the reversal of pro-tumor immune signature.DiscussionWe report for the first time, the association between immunological modifications in response to chemotherapy and the time of recurrence. Our findings provide novel opportunities to ultimately improve ovarian cancer patient survival

    Role of SNX16 in the Dynamics of Tubulo-Cisternal Membrane Domains of Late Endosomes

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    In this paper, we report that the PX domain-containing protein SNX16, a member of the sorting nexin family, is associated with late endosome membranes. We find that SNX16 is selectively enriched on tubulo-cisternal elements of this membrane system, whose highly dynamic properties and formation depend on intact microtubules. By contrast, SNX16 was not found on vacuolar elements that typically contain LBPA, and thus presumably correspond to multivesicular endosomes. We conclude that SNX16, together with its partner phosphoinositide, define a highly dynamic subset of late endosomal membranes, supporting the notion that late endosomes are organized in distinct morphological and functional regions. Our data also indicate that SNX16 is involved in tubule formation and cholesterol transport as well as trafficking of the tetraspanin CD81, suggesting that the protein plays a role in the regulation of late endosome membrane dynamics
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