271 research outputs found

    Tensile and compression properties of variously arranged porous Ti-6Al-4V additively manufactured structures via SLM

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    Abstract Additively manufactured porous structures find increasing applications in the biomedical context to produce orthopedic prosthesis and devices. In comparison with traditional bulk metallic implants, they permit to tailor the stiffness of the prosthesis to that of the surrounding bony tissues, thus limiting the onset of stress shielding and resulting implant loosening, and to favor the bone in-growth through the interconnected pores. Mechanical and biological properties of these structures are strongly influenced by the size and spatial arrangement of pores and struts. In the present work irregular and regular cellular as well as fully random porous structures are investigated through tensile and compression uniaxial tests. Specific point of novelty of this work is that, beside classical compressive tests, which are standard characterization methods for porous/ cellular materials, tensile tests are carried out. Mechanical tests are complemented with morphological analysis and porosity measurements. An attempt is made to find correlations between cell arrangements, porosity and mechanical properties

    Subordinate Actors’ Institutional Maintenance in Response to Coercive Reforms

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    Institutional work research shows how actors purposively create, maintain, and disrupt institutions. Failed or unintended consequences of institutional maintenance remain relatively unexplored, for two reasons. First, the role of coercive disruption actors (e.g., a state) has not been fully explored. Second, existing literature takes scant account of power and disregards the resistance tactics of subordinate actors. Drawing on a longitudinal case study of a migrant workers’ union in China, we show how subordinate actors were first able to maintain institutional arrangements followed by a maintenance failure under the disruption work performed by the authoritarian state. This study extends the institutional maintenance literature in two ways. First, subordinate actors can sustain institutions insofar as they collectively deploy superficial deference and hidden forms of resistance. Second, maintenance work is vulnerable in the sense that it is contingent on the systems of domination and the level of pressure exerted by the disruption actors

    Prioritizing the Role of Major Lipoproteins and Subfractions as Risk Factors for Peripheral Artery Disease.

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    BACKGROUND: Lipoprotein-related traits have been consistently identified as risk factors for atherosclerotic cardiovascular disease, largely on the basis of studies of coronary artery disease (CAD). The relative contributions of specific lipoproteins to the risk of peripheral artery disease (PAD) have not been well defined. We leveraged large-scale genetic association data to investigate the effects of circulating lipoprotein-related traits on PAD risk. METHODS: Genome-wide association study summary statistics for circulating lipoprotein-related traits were used in the mendelian randomization bayesian model averaging framework to prioritize the most likely causal major lipoprotein and subfraction risk factors for PAD and CAD. Mendelian randomization was used to estimate the effect of apolipoprotein B (ApoB) lowering on PAD risk using gene regions proxying lipid-lowering drug targets. Genes relevant to prioritized lipoprotein subfractions were identified with transcriptome-wide association studies. RESULTS: ApoB was identified as the most likely causal lipoprotein-related risk factor for both PAD (marginal inclusion probability, 0.86; P=0.003) and CAD (marginal inclusion probability, 0.92; P=0.005). Genetic proxies for ApoB-lowering medications were associated with reduced risk of both PAD (odds ratio,0.87 per 1-SD decrease in ApoB [95% CI, 0.84-0.91]; P=9Ă—10-10) and CAD (odds ratio,0.66 [95% CI, 0.63-0.69]; P=4Ă—10-73), with a stronger predicted effect of ApoB lowering on CAD (ratio of effects, 3.09 [95% CI, 2.29-4.60]; P<1Ă—10-6). Extra-small very-low-density lipoprotein particle concentration was identified as the most likely subfraction associated with PAD risk (marginal inclusion probability, 0.91; P=2.3Ă—10-4), whereas large low-density lipoprotein particle concentration was the most likely subfraction associated with CAD risk (marginal inclusion probability, 0.95; P=0.011). Genes associated with extra-small very-low-density lipoprotein particle and large low-density lipoprotein particle concentration included canonical ApoB pathway components, although gene-specific effects were variable. Lipoprotein(a) was associated with increased risk of PAD independently of ApoB (odds ratio, 1.04 [95% CI, 1.03-1.04]; P=1.0Ă—10-33). CONCLUSIONS: ApoB was prioritized as the major lipoprotein fraction causally responsible for both PAD and CAD risk. However, ApoB-lowering drug targets and ApoB-containing lipoprotein subfractions had diverse associations with atherosclerotic cardiovascular disease, and distinct subfraction-associated genes suggest possible differences in the role of lipoproteins in the pathogenesis of PAD and CAD

    Inappropriate prescribing and adverse drug events in older people

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    Inappropriate prescribing (IP) in older patients is highly prevalent and is associated with an increased risk of adverse drug events (ADEs), morbidity, mortality and healthcare utilisation. Consequently, IP is a major safety concern and with changing population demographics, it is likely to become even more prevalent in the future. IP can be detected using explicit or implicit prescribing indicators. Theoretically, the routine clinical application of these IP criteria could represent an inexpensive and time efficient method to optimise prescribing practice. However, IP criteria must be sensitive, specific, have good inter-rater reliability and incorporate those medications most commonly associated with ADEs in older people. To be clinically relevant, use of prescribing appropriateness tools must translate into positive patient outcomes, such as reduced rates of ADEs. To accurately measure these outcomes, a reliable method of assessing the relationship between the administration of a drug and an adverse clinical event is required. The Naranjo criteria are the most widely used tool for assessing ADE causality, however, they are often difficult to interpret in the context of older patients. ADE causality criteria that allow for the multiple co-morbidities and prescribed medications in older people are required. Ultimately, the current high prevalence of IP and ADEs is unacceptable. IP screening criteria need to be tested as an intervention to assess their impact on the incidence of ADEs in vulnerable older patients. There is a role for IP screening tools in everyday clinical practice. These should enhance, not replace good clinical judgement, which in turn should be based on sound pharmacogeriatric training

    Strategic Sensemaking and Political Connections in Unstable Institutional Contexts

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    Emerging economies are often characterized by pervasive institutional changes and resultant institutional voids. In the absence of strong formal institutions, firms rely on informal institutions to fill these voids. This article argues that the process of sensemaking for firms in turbulent environments is continuous and dependent on cyclical adjustments connecting performance via a feedback loop to scanning and interpretation. Far from being a one-time occurrence, environmental sensemaking is a process operating in accord with continuous environmental changes. This study’s findings derive from an in-depth analysis of a Russian pharmaceutical firm and an Indian telecommunications firm, and demonstrate that entrepreneurs make sense and gain legitimacy through political connections. The study further finds that improvements in institutional environments reduce the salience of political networks, thereby creating a choice for firms to rely on formed market mechanisms or continue along the path of political connections that evolve to public–private partnerships

    Cross-trait analyses with migraine reveal widespread pleiotropy and suggest a vascular component to migraine headache

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    Background: Nearly a fifth of the world's population suffer from migraine headache, yet risk factors for this disease are poorly characterized. Methods: To further elucidate these factors, we conducted a genetic correlation analysis using cross-trait linkage disequilibrium (LD) score regression between migraine headache and 47 traits from the UK Biobank. We then tested for possible causality between these phenotypes and migraine, using Mendelian randomization. In addition, we attempted replication of our findings in an independent genome-wide association study (GWAS) when available. Results: We report multiple phenotypes with genetic correlation (P < 1.06 Ă— 10-3) with migraine, including heart disease, type 2 diabetes, lipid levels, blood pressure, autoimmune and psychiatric phenotypes. In particular, we find evidence that blood pressure directly contributes to migraine and explains a previously suggested causal relationship between calcium and migraine. Conclusions: This is the largest genetic correlation analysis of migraine headache to date, both in terms of migraine GWAS sample size and the number of phenotypes tested. We find that migraine has a shared genetic basis with a large number of traits, indicating pervasive pleiotropy at migraine-associated loci.Peer reviewe
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