10 research outputs found

    On-orbit structural dynamic performance of a 15-meter microwave radiometer antenna

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    The on-orbit structural dynamic performance of a microwave radiometer antenna for Earth science applications is addressed. The radiometer is one of the Earth-observing instruments aboard a proposed geostationary platform as part of the Mission to the Planet Earth. A sequential approach is presented for assessing the ability of an antenna structure to retain its geometric shape subject to a representative onboard disturbance. This approach includes establishing the structural requirements of the antenna, developing the structural and disturbance models, performing modal and forced response analyses, and evaluating the resulting distortions in terms of the antenna's ability to meet stringent structural performance requirements. Two antenna configurations are discussed: free-flying and platform-mounted. These configurations are analyzed for a representative disturbance function which simulates rotation of the subreflector in order to perform a raster-type scan of the Earth disk. Results show that the scanning maneuver modeled would not induce antenna structural errors outside the specified limits

    Creating Online Lessons: A Faculty Development Seminar Series

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    The World Wide Web is being used increasingly to deliver instruction in medical education. Consequently, there is a need to train faculty in developing and implementing online instruction. We developed and implemented a seminar series to teach faculty to create educationally sound, well designed online instruction. Instruction was delivered to 15 participants via a six session seminar on developing web based lessons, supplemented with web-based instruction. First, the participants learned the basics of instructional design via a web based module. They then completed content outlines for their online lessons prior to the first seminar. Lesson development, web site development and the use of a web based instructional shell to implement the online lessons were each taught in two two hour sessions. Eight participants developed online lessons and four actually implemented them. Feedback was mostly positive, with suggestions for improvement. All eight participants who completed the series said they would recommend it to their colleagues. Because a longitudinal workshop type of seminar series requires a large amount of participant time outside of class, a six month seminar series may be too long. It is important at the beginning of the series to help participants select topics suitable for online instruction and to help them narrow their topics. We may change the attendance guidelines so faculty would attend only the session on instructional design and have their staff attend the technical sessions on web site design, HTML editing and online course delivery systems. This would better match the actual practice of faculty designing the instruction and staff developing it

    Deciphering mollusc shell production: the roles of genetic mechanisms through to ecology, aquaculture and biomimetics

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    Most molluscs possess shells, constructed from a vast array of microstructures and architectures. The fully formed shell is composed of calcite or aragonite. These CaCO3 crystals form complex biocomposites with proteins, which although typically less than 5% of total shell mass, play significant roles in determining shell microstructure. Despite much research effort, large knowledge gaps remain in how molluscs construct and maintain their shells, and how they produce such a great diversity of forms. Here we synthesize results on how shell shape, microstructure, composition and organic content vary among, and within, species in response to numerous biotic and abiotic factors. At the local level, temperature, food supply and predation cues significantly affect shell morphology, whilst salinity has a much stronger influence across latitudes. Moreover, we emphasize how advances in genomic technologies [e.g. restriction site-associated DNA sequencing (RAD-Seq) and epigenetics] allow detailed examinations of whether morphological changes result from phenotypic plasticity or genetic adaptation, or a combination of these. RAD-Seq has already identified single nucleotide polymorphisms associated with temperature and aquaculture practices, whilst epigenetic processes have been shown significantly to modify shell construction to local conditions in, for example, Antarctica and New Zealand. We also synthesize results on the costs of shell construction and explore how these affect energetic trade-offs in animal metabolism. The cellular costs are still debated, with CaCO3 precipitation estimates ranging from 1-2 J/mg to 17-55 J/mg depending on experimental and environmental conditions. However, organic components are more expensive (~29 J/mg) and recent data indicate transmembrane calcium ion transporters can involve considerable costs. This review emphasizes the role that molecular analyses have played in demonstrating multiple evolutionary origins of biomineralization genes. Although these are characterized by lineage-specific proteins and unique combinations of co-opted genes, a small set of protein domains have been identified as a conserved biomineralization tool box. We further highlight the use of sequence data sets in providing candidate genes for in situ localization and protein function studies. The former has elucidated gene expression modularity in mantle tissue, improving understanding of the diversity of shell morphology synthesis. RNA interference (RNAi) and clustered regularly interspersed short palindromic repeats - CRISPR-associated protein 9 (CRISPR-Cas9) experiments have provided proof of concept for use in the functional investigation of mollusc gene sequences, showing for example that Pif (aragonite-binding) protein plays a significant role in structured nacre crystal growth and that the Lsdia1 gene sets shell chirality in Lymnaea stagnalis. Much research has focused on the impacts of ocean acidification on molluscs. Initial studies were predominantly pessimistic for future molluscan biodiversity. However, more sophisticated experiments incorporating selective breeding and multiple generations are identifying subtle effects and that variability within mollusc genomes has potential for adaption to future conditions. Furthermore, we highlight recent historical studies based on museum collections that demonstrate a greater resilience of molluscs to climate change compared with experimental data. The future of mollusc research lies not solely with ecological investigations into biodiversity, and this review synthesizes knowledge across disciplines to understand biomineralization. It spans research ranging from evolution and development, through predictions of biodiversity prospects and future-proofing of aquaculture to identifying new biomimetic opportunities and societal benefits from recycling shell products.FCT: UID/Multi/04326/2019; European Marine Biological Research Infrastructure Cluster-EMBRIC (EU H2020 research and innovation program) 654008; European Union Seventh Framework Programme [FP7] ITN project 'CACHE: Calcium in a Changing Environment' under REA 60505; NERC Natural Environment Research Council NE/J500173/1info:eu-repo/semantics/publishedVersio

    Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

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    BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

    Study Skills and Academic Performance among Second-Year Medical Students in Problem-Based Learning

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    Purpose: This research study highlights the relationship between study aid use and exam performance of second year medical students. It also discusses how students used study aids in preparing for PBL exams and whether students who used others ’ study aids performed as well as students who created their own. Methods: A questionnaire was distributed to second-year medical students after completion of their exam. The data from the questionnaire were linked to students ’ examination scores and other academic indicators. Results: The study habits were more similar than different when compared by exam performance. A majority of students used study aids as a memory aid or for review, but students who performed in the top third of the class were less likely to use them at all. Pre-existing differences related to academic achievement and study strategies were found when students at the top, middle and bottom of exam performance were compared. Conclusions: A better understanding of the differences in study habits and study aid use in relation to examination performance can help in providing future students with appropriate academi

    Glioma pathogenesis-related 1-Like 1 is testis enriched, dynamically modified, and redistributed during male germ cell maturation and has a potential role in sperm-oocyte binding

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    The glioma pathogenesis-related 1 (GLIPR1) family consists of three genes [GLIPR1, GLIPR1-like 1(GLIPR1L1), and GLIPR1-like 2 (GLIPR1L2)] and forms a distinct subgroup within the cysteine-rich secretory protein (CRISP), antigen 5, and pathogenesis-related 1 (CAP) superfamily. CAP superfamily proteins are found in phyla ranging from plants to humans and, based largely on expression and limited functional studies, are hypothesized to have roles in carcinogenesis, immunity, cell adhesion, and male fertility. Specifically data from a number of systems suggests that sequences within the C-terminal CAP domain of CAP proteins have the ability to promote cell-cell adhesion. Herein we cloned mouse Glipr1l1 and have shown it has a testis-enriched expression profile. GLIPR1L1 is posttranslationally modified by N-linked glycosylation during spermatogenesis and ultimately becomes localized to the connecting piece of elongated spermatids and sperm. After sperm capacitation, however, GLIPR1L1 is also localized to the anterior regions of the sperm head. Zona pellucida binding assays indicate that GLIPR1L1 has a role in the binding of sperm to the zona pellucida surrounding the oocyte. These data suggest that, along with other members of the CAP superfamily and several other proteins, GLIPR1L1 is involved in the binding of sperm to the oocyte complex. Collectively these data further strengthen the role of CAP domain-containing proteins in cellular adhesion and propose a mechanism whereby CAP proteins show overlapping functional significance during fertilization

    Prophylactic biological mesh reinforcement versus standard closure of stoma site (ROCSS): a multicentre, randomised controlled trial

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    Background: Closure of an abdominal stoma, a common elective operation, is associated with frequent complications; one of the commonest and impactful is incisional hernia formation. We aimed to investigate whether biological mesh (collagen tissue matrix) can safely reduce the incidence of incisional hernias at the stoma closure site. Methods: In this randomised controlled trial (ROCSS) done in 37 hospitals across three European countries (35 UK, one Denmark, one Netherlands), patients aged 18 years or older undergoing elective ileostomy or colostomy closure were randomly assigned using a computer-based algorithm in a 1:1 ratio to either biological mesh reinforcement or closure with sutures alone (control). Training in the novel technique was standardised across hospitals. Patients and outcome assessors were masked to treatment allocation. The primary outcome measure was occurrence of clinically detectable hernia 2 years after randomisation (intention to treat). A sample size of 790 patients was required to identify a 40% reduction (25% to 15%), with 90% power (15% drop-out rate). This study is registered with ClinicalTrials.gov, NCT02238964. Findings: Between Nov 28, 2012, and Nov 11, 2015, of 1286 screened patients, 790 were randomly assigned. 394 (50%) patients were randomly assigned to mesh closure and 396 (50%) to standard closure. In the mesh group, 373 (95%) of 394 patients successfully received mesh and in the control group, three patients received mesh. The clinically detectable hernia rate, the primary outcome, at 2 years was 12% (39 of 323) in the mesh group and 20% (64 of 327) in the control group (adjusted relative risk [RR] 0·62, 95% CI 0·43–0·90; p=0·012). In 455 patients for whom 1 year postoperative CT scans were available, there was a lower radiologically defined hernia rate in mesh versus control groups (20 [9%] of 229 vs 47 [21%] of 226, adjusted RR 0·42, 95% CI 0·26–0·69; p<0·001). There was also a reduction in symptomatic hernia (16%, 52 of 329 vs 19%, 64 of 331; adjusted relative risk 0·83, 0·60–1·16; p=0·29) and surgical reintervention (12%, 42 of 344 vs 16%, 54 of 346: adjusted relative risk 0·78, 0·54–1·13; p=0·19) at 2 years, but this result did not reach statistical significance. No significant differences were seen in wound infection rate, seroma rate, quality of life, pain scores, or serious adverse events. Interpretation: Reinforcement of the abdominal wall with a biological mesh at the time of stoma closure reduced clinically detectable incisional hernia within 24 months of surgery and with an acceptable safety profile. The results of this study support the use of biological mesh in stoma closure site reinforcement to reduce the early formation of incisional hernias. Funding: National Institute for Health Research Research for Patient Benefit and Allergan

    [The effect of low-dose hydrocortisone on requirement of norepinephrine and lactate clearance in patients with refractory septic shock].

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    Regular Wine Consumption in Chronic Heart Failure: Impact on Outcomes, Quality of Life, and Circulating Biomarkers

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    Background-Moderate, regular alcohol consumption is generally associated with a lower risk of cardiovascular events but data in patients with chronic heart failure are scarce. We evaluated the relations between wine consumption, health status, circulating biomarkers, and clinical outcomes in a large Italian population of patients with chronic heart failure enrolled in a multicenter clinical trial. Methods and Results-A brief questionnaire on dietary habits was administered at baseline to 6973 patients enrolled in the Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza Cardiaca-Heart Failure (GISSI-HF) trial. The relations between wine consumption, fatal and nonfatal clinical end points, quality of life, symptoms of depression, and circulating biomarkers of cardiac function and inflammation (in subsets of patients) were evaluated with simple and multivariable-adjusted statistical models. Almost 56% of the patients reported drinking at least 1 glass of wine per day. After adjustment, clinical outcomes were not significantly different in the predefined 4 groups of wine consumption. However, patients with more frequent wine consumption had a significantly better perception of health status (Kansas City Cardiomyopathy Questionnaire score, adjusted P&lt;0.0001), less frequent symptoms of depression (Geriatric Depression Scale, adjusted P=0.01), and lower plasma levels of biomarkers of vascular inflammation (osteoprotegerin and C-terminal proendothelin-1, adjusted P&lt;0.0001, and pentraxin-3, P=0.01) after adjusting for possible confounders. Conclusions-We show for the first time in a large cohort of patients with chronic heart failure that moderate wine consumption is associated with a better perceived and objective health status, lower prevalence of depression, and less vascular inflammation, but does not translate into more favorable clinical 4-year outcomes. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT0033633
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