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Sökning: WFRF:(Wyman J)

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  • Bayley, PJ, et al. (författare)
  • 2013 SYR Accepted Poster Abstracts
  • 2013
  • Ingår i: International journal of yoga therapy. - 1531-2054. ; 23:1, s. 32-53
  • Tidskriftsartikel (refereegranskat)
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  • Nicolas, Aude, et al. (författare)
  • Genome-wide Analyses Identify KIF5A as a Novel ALS Gene
  • 2018
  • Ingår i: Neuron. - : Cell Press. - 0896-6273 .- 1097-4199. ; 97:6, s. 1268-1283.e6
  • Tidskriftsartikel (refereegranskat)abstract
    • To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.
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  • Cotofana, S., et al. (författare)
  • Relationship between knee pain and the presence, location, size and phenotype of femorotibial denuded areas of subchondral bone as visualized by MRI
  • 2013
  • Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 21:9, s. 1214-1222
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Conflicting associations between imaging biomarkers and pain in knee osteoarthritis (OA) have been reported. A relation between pain and denuded areas of subchondral bone (dABs) has been suggested and this study explores this relationship further by relating the presence, phenotype, location and size of dABs to different measures of knee pain. Methods: 633 right knees from the Osteoarthritis Initiative (OAI) (250 men, age 61.7 +/- 9.6 yrs, BMI 29.4 +/- 4.7 kg/m(2)) were included. Manual segmentation of the femorotibial cartilage plates was performed on 3 T coronal fast low angle shot with water excitation (FLASHwe) images. dABs were defined as areas where the subchondral bone was uncovered by cartilage. The following measures of pain were used: weightbearing-, non-weightbearing-, moderate-to-severe-, infrequent- and frequent knee pain. Results: Using pain measures from subjects without dABs as a reference, those with at least one dAB had a 1.64-fold higher prevalence ratio [PR, 95% confidence interval (CI) 1.24-2.18] to have frequent and 1.45-fold higher for moderate-to-severe knee pain (95% CI 1.13-1.85). Subjects with dABs in central subregions had a 1.53-fold increased prevalence of having weightbearing pain (95% Cl 1.20-1.97), especially when the central subregion was moderately (>10%) denuded (PR 1.81, 95% CI 135-2.42). Individuals with cartilage-loss-type dABs had a slightly higher prevalence (PR 1.13, 95% CI 1.00-1.27) of having frequent knee pain compared to individuals with intra-chondral-osteophyte-type dABs. Conclusion: This study supports a positive relation between femorotibial dABs and knee pain, especially when the dABs are located centrally (i.e., in weightbearing regions) or when the respective central subregion is moderately denuded. (C) 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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  • Frid, Casey J., et al. (författare)
  • Low-wealth entrepreneurs and access to external financing
  • 2016
  • Ingår i: International Journal of Entrepreneurial Behaviour & Research. - : Emerald Group Publishing Limited. - 1355-2554 .- 1758-6534. ; 22:4, s. 531-555
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose– The purpose of this paper is to explore the relationship between low-wealth business founders in the USA and external startup funding. Specifically, the authors test whether a founders’ low personal net worth is correlated with a lower probability of acquiring funding from outside sources during the business creation process.Design/methodology/approach– The authors use a double-hurdle Cragg model to jointly estimate: first, the decision to acquire external financing; and second, the amount received. The sample is the US-based Panel Study of Entrepreneurial Dynamics II (PSED II). The PSED II tracks business founders attempting to start ventures from 2005 to 2012.Findings– Receipt of outside financing during business formation is largely determined by the business founder’s personal finances (controlling for human capital, venture type and industry, and whether money was sought in the first place). A higher household net worth results in larger amounts of external funding received. Low-wealth business founders, therefore, are less likely to get external funds, and they receive lower amounts when they do. The disparity between low-and high-wealth business founders is more pronounced for formal, monitored sources of external financing such as bank loans.Research limitations/implications– Because the study eliminates survivor bias by using a nationally representative sample of business founders who are in the venture creation process, the findings apply to both successful business founders and those who disengaged during the business creation process. The authors offer insights into the sources and amounts of external funds acquired by individuals across all levels of wealth. The authors accomplish this by disaggregating business founders into wealth quintiles. The study demonstrates the importance of personal wealth as a factor in acquiring external startup financing compared to human capital, industry, or personal characteristics.Social implications– If the ability to acquire external funding is significantly constrained, the quality of the opportunity and the skill of the business founder may be less a determinant of success at creating a new business as prior studies have suggested. Consequently, entrepreneurship (as measured by business formation) as a path toward upward, socioeconomic mobility will be afforded only to those individuals with sufficient financial endowments at the outset.Originality/value– Unlike prior studies, the data used are not subject to survivor bias or an underrepresentation of self-employment. The statistical model jointly estimates acquisition of financing and the amount received. This resolves selection and censoring problems. Finally, the dependent variables directly measure liquidity constraints in the context of business formation, that is, before a new venture is created. Prior research contexts have typically studied existing businesses, and are therefore not true examinations of conditions affecting business creation.
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  • Frid, Casey J., et al. (författare)
  • The influence of financial 'skin in the game' on new venture creation
  • 2015
  • Ingår i: Academy of Entrepreneurship Journal. - 1087-9595 .- 1528-2686. ; 21:2, s. 1-14
  • Tidskriftsartikel (refereegranskat)abstract
    • A common theme in entrepreneurship research is that the founder must be committed in order for a new venture to succeed. Although investments of time and sweat equity can indicate commitment, external stakeholders may prefer founders who have made a significant, personal financial stake in their nascent ventures. This personal financial commitment is known as "skin in the game." Founders that invest more of their own money into their ventures signal greater commitment to potential business partners, suppliers, and resource providers.This study examines the amount of personal funds invested by 1,214 nascent entrepreneurs in the United States, between the years of 2005 and 2012. Findings demonstrate that the dollar amount of personal money invested prior to launch does not significantly impact the creation of new firms. However, nascent entrepreneurs that invest larger amounts as a proportion of their net income are more likely to succeed and are less likely to disengage from the process. Personal funds invested as a proportion of net income may therefore be a better measure of future success than the precise amount. This study also shows that the founder's human capital, perceptions of community support, and industry characteristics influence startup outcomes.
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  • Gleason, Carey E, et al. (författare)
  • Alzheimer's disease biomarkers in Black and non-Hispanic White cohorts: A contextualized review of the evidence.
  • 2022
  • Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 18:8, s. 1545-1564
  • Tidskriftsartikel (refereegranskat)abstract
    • Black Americans are disproportionately affected by dementia. To expand our understanding of mechanisms of this disparity, we look to Alzheimer's disease (AD) biomarkers. In this review, we summarize current data, comparing the few studies presenting these findings. Further, we contextualize the data using two influential frameworks: the National Institute on Aging-Alzheimer's Association (NIA-AA) Research Framework and NIA's Health Disparities Research Framework. The NIA-AA Research Framework provides a biological definition of AD that can be measured in vivo. However, current cut-points for determining pathological versus non-pathological status were developed using predominantly White cohorts-a serious limitation. The NIA's Health Disparities Research Framework is used to contextualize findings from studies identifying racial differences in biomarker levels, because studying biomakers in isolation cannot explain or reduce inequities. We offer recommendations to expand study beyond initial reports of racial differences. Specifically, life course experiences associated with racialization and commonly used study enrollment practices may better account for observations than exclusively biological explanations.
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  • Rodriguez-Porcel, F, et al. (författare)
  • Clinical outcome measures in dementia with Lewy bodies trials: critique and recommendations
  • 2022
  • Ingår i: Translational neurodegeneration. - : Springer Science and Business Media LLC. - 2047-9158. ; 11:1, s. 24-
  • Tidskriftsartikel (refereegranskat)abstract
    • The selection of appropriate outcome measures is fundamental to the design of any successful clinical trial. Although dementia with Lewy bodies (DLB) is one of the most common neurodegenerative conditions, assessment of therapeutic benefit in clinical trials often relies on tools developed for other conditions, such as Alzheimer’s or Parkinson’s disease. These may not be sufficiently valid or sensitive to treatment changes in DLB, decreasing their utility. In this review, we discuss the limitations and strengths of selected available tools used to measure DLB-associated outcomes in clinical trials and highlight the potential roles for more specific objective measures. We emphasize that the existing outcome measures require validation in the DLB population and that DLB-specific outcomes need to be developed. Finally, we highlight how the selection of outcome measures may vary between symptomatic and disease-modifying therapy trials.
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