2,531 research outputs found

    Relational Exchange in Nonprofits: The Role of Identity Saliency and Relationship Satisfaction

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    Research and practice in nonprofit fundraising has increasingly been focused on the benefits of relational exchange. This dissertation examines relationships between donors and nonprofit organizations and their impact on the charitable giving levels using identity salience and relationship satisfaction as key mediators of nonprofit relational exchange. Previous research has shown that there are a plethora of charitable giving motivations that contribute to supportive behaviors in the nonprofit context; however, this research does not provide a comprehensive understanding of the intervening variables. This study modified previous studies by introducing relationship satisfaction in addition to identity saliency, as mediating constructs. Results confirm that both identity saliency and relationship satisfaction partially mediate charitable giving motivations and charitable giving. Additionally, perceived organizational performance, emotional utility, and parental socialization and youth participation were significantly related to identity salience. Finally, perceived organizational performance, emotional utility, and satisfaction with the solicitation process were found to significantly related to relationship satisfaction

    Embedding clinical interventions into observational studies

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    Novel approaches to observational studies and clinical trials could improve the cost-effectiveness and speed of translation of research. Hybrid designs that combine elements of clinical trials with observational registries or cohort studies should be considered as part of a long-term strategy to transform clinical trials and epidemiology, adapting to the opportunities of big data and the challenges of constrained budgets. Important considerations include study aims, timing, breadth and depth of the existing infrastructure that can be leveraged, participant burden, likely participation rate and available sample size in the cohort, required sample size for the trial, and investigator expertise. Community engagement and stakeholder (including study participants) support are essential for these efforts to succeed

    Leaning in to Address Sleep Disturbances and Sleep Disorders in Department of Defense and Defense Health Agency

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    Letter to the Editor, Military Medicine, 187, 5/6:155, 202217 USC 105 interim-entered record; under review.The article of record as published may be found at http://dx.doi.org/10.1177/0018720820906050In their article entitled, “Engaging Stakeholders to Optimize Sleep Disorders Management in the U.S. Military: A Qualitative Analysis,” Abdelwadoud and colleagues conducted focus groups of service members, primary care managers (PCMs), and administrative stakeholders about their perceptions, experiences, roles in sleep management, stated education needs, and management of sleep disorders.1 The qualitative methods are rigorous, and the findings reinforce and nuance prior results, especially regarding key requirements from PCMs. We feel compelled, however, to further nuance the authors’ conclusion that “current military sleep management practices are neither satisfactory nor maximally effective” and offer specific examples of actions taken by the Department of Defense (DoD) and Defense Health Agency (DHA) in recognition of the significance of optimal sleep in combat readiness and overall health of service members. We offer here a succinct list of concrete efforts to support and implement substantial clinical, operational, research, or educational efforts by the DoD or DHA to improve sleep in service members and associated clinical challenges in this unique population.Identified in text as U.S. Government work

    The incidence of human papillomavirus infection following treatment for cervical neoplasia: A systematic review

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    To systematically review the published literature in order to estimate the incidence and describe the variability of human papillomavirus (HPV) infection in women following treatment for cervical neoplasia

    Quantifying pelagic phosphorus regeneration using three methods in lakes of varying productivity

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    Phosphorus (P) is often a limiting nutrient in freshwater ecosystems, and understanding P dynamics in lakes is critical for eutrophication management. Pelagic P regeneration can support a large fraction of primary production in stratified freshwaters. Various techniques have been used to quantify pelagic P regeneration including (1) P mass balance supply–demand, (2) regression using total P as a predictor, and, more recently, (3) whole-lake metabolism calculated from high-frequency dissolved oxygen (DO) data. To our knowledge no study comparing these methods in multiple lakes has been performed. To compare these 3 approaches, we investigated 3 Global Lake Ecological Observatory Network (GLEON) lakes that differ in productivity: Acton, a Midwestern USA hypereutrophic reservoir; and 2 Northeastern USA glacial lakes, oligotrophic Giles and mesotrophic/dystrophic Lacawac. In Acton, we used all 3 methods, but for Giles and Lacawac we used only the total P regression and metabolism techniques. Our results show the best agreement among methods in the mesotrophic lake, whereas the metabolism approach underestimated regeneration in the oligotrophic lake and overestimated regeneration in the hypereutrophic reservoir compared with other methods. P regeneration rates for the hypereutrophic reservoir were the most sensitive to the metabolism-based input parameters. Our study illustrates a novel use of high-frequency DO data, which are commonly collected on many GLEON buoys, to understand lake nutrient dynamics

    The Erotic and the Vulgar: Visual Culture and Organized Labor's Critique of U.S. Hegemony in Occupied Japan

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    This essay engages the colonial legacy of postwar Japan by arguing that the political cartoons produced as part of the postwar Japanese labor movement’s critique of U.S. cultural hegemony illustrate how gendered discourses underpinned, and sometimes undermined, the ideologies formally represented by visual artists and the organizations that funded them. A significant component of organized labor’s propaganda rested on a corpus of visual media that depicted women as icons of Japanese national culture. Japan’s most militant labor unions were propagating anti-imperialist discourses that invoked an engendered/endangered nation that accentuated the importance of union roles for men by subordinating, then eliminating, union roles for women

    Anti-tumour necrosis factor therapy for Dupuytren's Disease: a randomised dose response proof of concept phase 2a clinical trial

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    Background Dupuytren's disease is a common fibrotic condition of the hand that causes irreversible flexion contractures of the fingers, with no approved therapy for early stage disease. Our previous analysis of surgically-excised tissue defined tumour necrosis factor (TNF) as a potential therapeutic target. Here we assessed the efficacy of injecting nodules of Dupuytren's disease with a TNF inhibitor. Methods Patients were randomised to receive adalimumab on one occasion in dose cohorts of 15 mg in 0.3 ml, 35 mg in 0.7 ml, or 40 mg in 0.4 ml, or an equivalent volume of placebo in a 3:1 ratio. Two weeks later the injected tissue was surgically excised and analysed. The primary outcome measure was levels of mRNA expression for α-smooth muscle actin (ACTA2). Secondary outcomes included levels of α-SMA and collagen proteins. The trial was registered with ClinicalTrial.gov (NCT03180957) and the EudraCT (2015-001780-40). Findings We recruited 28 patients, 8 assigned to the 15 mg, 12 to the 35 mg and 8 to the 40 mg adalimumab cohorts. There was no change in mRNA levels for ACTA2, COL1A1, COL3A1 and CDH11. Levels of α-SMA protein expression in patients treated with 40 mg adalimumab (1.09 ± 0.09 ng per μg of total protein) were significantly lower (p = 0.006) compared to placebo treated patients (1.51 ± 0.09 ng/μg). The levels of procollagen type I protein expression were also significantly lower (p < 0.019) in the sub group treated with 40 mg adalimumab (474 ± 84 pg/μg total protein) compared with placebo (817 ± 78 pg/μg). There were two serious adverse events, both considered unrelated to the study drug. Interpretation In this dose-ranging study, injection of 40 mg of adalimumab in 0.4 ml resulted in down regulation of the myofibroblast phenotype as evidenced by reduction in expression of α-SMA and type I procollagen proteins at 2 weeks. These data form the basis of an ongoing phase 2b clinical trial assessing the efficacy of intranodular injection of 40 mg adalimumab in 0.4 ml compared to an equivalent volume of placebo in patients with early stage Dupuytren's disease

    Targeted genetic testing for familial hypercholesterolaemia using next generation sequencing:a population-based study

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    Background&lt;p&gt;&lt;/p&gt; Familial hypercholesterolaemia (FH) is a common Mendelian condition which, untreated, results in premature coronary heart disease. An estimated 88% of FH cases are undiagnosed in the UK. We previously validated a method for FH mutation detection in a lipid clinic population using next generation sequencing (NGS), but this did not address the challenge of identifying index cases in primary care where most undiagnosed patients receive healthcare. Here, we evaluate the targeted use of NGS as a potential route to diagnosis of FH in a primary care population subset selected for hypercholesterolaemia.&lt;p&gt;&lt;/p&gt; Methods&lt;p&gt;&lt;/p&gt; We used microfluidics-based PCR amplification coupled with NGS and multiplex ligation-dependent probe amplification (MLPA) to detect mutations in LDLR, APOB and PCSK9 in three phenotypic groups within the Generation Scotland: Scottish Family Health Study including 193 individuals with high total cholesterol, 232 with moderately high total cholesterol despite cholesterol-lowering therapy, and 192 normocholesterolaemic controls.&lt;p&gt;&lt;/p&gt; Results&lt;p&gt;&lt;/p&gt; Pathogenic mutations were found in 2.1% of hypercholesterolaemic individuals, in 2.2% of subjects on cholesterol-lowering therapy and in 42% of their available first-degree relatives. In addition, variants of uncertain clinical significance (VUCS) were detected in 1.4% of the hypercholesterolaemic and cholesterol-lowering therapy groups. No pathogenic variants or VUCS were detected in controls.&lt;p&gt;&lt;/p&gt; Conclusions&lt;p&gt;&lt;/p&gt; We demonstrated that population-based genetic testing using these protocols is able to deliver definitive molecular diagnoses of FH in individuals with high cholesterol or on cholesterol-lowering therapy. The lower cost and labour associated with NGS-based testing may increase the attractiveness of a population-based approach to FH detection compared to genetic testing with conventional sequencing. This could provide one route to increasing the present low percentage of FH cases with a genetic diagnosis

    Mapping interactions with the chaperone network reveals factors that protect against tau aggregation.

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    A network of molecular chaperones is known to bind proteins ('clients') and balance their folding, function and turnover. However, it is often unclear which chaperones are critical for selective recognition of individual clients. It is also not clear why these key chaperones might fail in protein-aggregation diseases. Here, we utilized human microtubule-associated protein tau (MAPT or tau) as a model client to survey interactions between ~30 purified chaperones and ~20 disease-associated tau variants (~600 combinations). From this large-scale analysis, we identified human DnaJA2 as an unexpected, but potent, inhibitor of tau aggregation. DnaJA2 levels were correlated with tau pathology in human brains, supporting the idea that it is an important regulator of tau homeostasis. Of note, we found that some disease-associated tau variants were relatively immune to interactions with chaperones, suggesting a model in which avoiding physical recognition by chaperone networks may contribute to disease
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