1. |
- Fenstermacher, M.E., et al.
(author)
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DIII-D research advancing the physics basis for optimizing the tokamak approach to fusion energy
- 2022
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In: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 62:4
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Journal article (peer-reviewed)abstract
- DIII-D physics research addresses critical challenges for the operation of ITER and the next generation of fusion energy devices. This is done through a focus on innovations to provide solutions for high performance long pulse operation, coupled with fundamental plasma physics understanding and model validation, to drive scenario development by integrating high performance core and boundary plasmas. Substantial increases in off-axis current drive efficiency from an innovative top launch system for EC power, and in pressure broadening for Alfven eigenmode control from a co-/counter-I p steerable off-axis neutral beam, all improve the prospects for optimization of future long pulse/steady state high performance tokamak operation. Fundamental studies into the modes that drive the evolution of the pedestal pressure profile and electron vs ion heat flux validate predictive models of pedestal recovery after ELMs. Understanding the physics mechanisms of ELM control and density pumpout by 3D magnetic perturbation fields leads to confident predictions for ITER and future devices. Validated modeling of high-Z shattered pellet injection for disruption mitigation, runaway electron dissipation, and techniques for disruption prediction and avoidance including machine learning, give confidence in handling disruptivity for future devices. For the non-nuclear phase of ITER, two actuators are identified to lower the L-H threshold power in hydrogen plasmas. With this physics understanding and suite of capabilities, a high poloidal beta optimized-core scenario with an internal transport barrier that projects nearly to Q = 10 in ITER at ∼8 MA was coupled to a detached divertor, and a near super H-mode optimized-pedestal scenario with co-I p beam injection was coupled to a radiative divertor. The hybrid core scenario was achieved directly, without the need for anomalous current diffusion, using off-axis current drive actuators. Also, a controller to assess proximity to stability limits and regulate β N in the ITER baseline scenario, based on plasma response to probing 3D fields, was demonstrated. Finally, innovative tokamak operation using a negative triangularity shape showed many attractive features for future pilot plant operation.
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2. |
- Impellizzeri, Franco M., et al.
(author)
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Patient-reported outcome measures for hip-related pain : A review of the available evidence and a consensus statement from the International Hip-related Pain Research Network, Zurich 2018
- 2020
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In: British journal of sports medicine. - : BMJ. - 0306-3674 .- 1473-0480. ; 54:14, s. 848-857
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Research review (peer-reviewed)abstract
- Hip-related pain is a well-recognised complaint among active young and middle-aged active adults. People experiencing hip-related disorders commonly report pain and reduced functional capacity, including difficulties in executing activities of daily living. Patient-reported outcome measures (PROMs) are essential to accurately examine and compare the effects of different treatments on disability in those with hip pain. In November 2018, 38 researchers and clinicians working in the field of hip-related pain met in Zurich, Switzerland for the first International Hip-related Pain Research Network meeting. Prior to the meeting, evidence summaries were developed relating to four prioritised themes. This paper discusses the available evidence and consensus process from which recommendations were made regarding the appropriate use of PROMs to assess disability in young and middle-aged active adults with hip-related pain. Our process to gain consensus had five steps: (1) systematic review of systematic reviews; (2) preliminary discussion within the working group; (3) update of the more recent high-quality systematic review and examination of the psychometric properties of PROMs according to established guidelines; (4) formulation of the recommendations considering the limitations of the PROMs derived from the examination of their quality; and (5) voting and consensus. Out of 102 articles retrieved, 6 systematic reviews were selected and assessed for quality according to AMSTAR 2 (A MeaSurement Tool to Assess systematic Reviews). Two showed moderate quality. We then updated the most recent review. The updated literature search resulted in 10 additional studies that were included in the qualitative synthesis. The recommendations based on evidence summary and PROMs limitations were presented at the consensus meeting. The group makes the following recommendations: (1) the Hip and Groin Outcome Score (HAGOS) and the International Hip Outcome Tool (iHOT) instruments (long and reduced versions) are the most appropriate PROMs to use in young and middle-aged active adults with hip-related pain; (2) more research is needed into the utility of the HAGOS and the iHOT instruments in a non-surgical treatment context; and (3) generic quality of life measures such as the EuroQoL-5 Dimension Questionnaire and the Short Form Health Survey-36 may add value for researchers and clinicians in this field. We conclude that as none of the instruments shows acceptable quality across various psychometric properties, more methods studies are needed to further evaluate the validity of these PROMS-the HAGOS and iHOT-as well as the other (currently not recommended) PROMS.
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3. |
- Kemp, Joanne L., et al.
(author)
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Physiotherapist-led treatment for young to middle-aged active adults with hip-related pain : Consensus recommendations from the International Hip-related Pain Research Network, Zurich 2018
- 2020
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In: British journal of sports medicine. - : BMJ. - 0306-3674 .- 1473-0480. ; 54:9, s. 504-511
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Journal article (peer-reviewed)abstract
- The 1st International Hip-related Pain Research Network meeting discussed four prioritised themes concerning hip-related pain in young to middle-aged adults: (1) diagnosis and classification of hip-related pain; (2) patient-reported outcome measures for hip-related pain; (3) measurement of physical capacity for hip-related pain; (4) physiotherapist-led treatment for hip-related pain. Thirty-eight expert researchers and clinicians working in the field of hip-related pain attended the meeting. This manuscript relates to the theme of physiotherapist-led treatments for hip-related pain. A systematic review on the efficacy of physiotherapist-led interventions for hip-related pain (published separately) was conducted and found that strong evidence for physiotherapist-led treatments was lacking. Prior to the meeting, draft consensus recommendations for consideration in the meeting were also developed based on the systematic review. The draft consensus recommendations were presented to all of the meeting participants via email, at least 1 week prior to the meeting. At the meeting, these recommendations were discussed, revised and voted on. Six recommendations for clinical practice and five recommendations for research were included and all gained consensus. Recommendations for clinical practice were that (i) Exercise-based treatments are recommended for people with hip-related pain. (ii) Exercise-based treatment should be at least 3 months duration. (iii) Physiotherapist-led rehabilitation after hip surgery should be undertaken. (iv) Patient-reported outcome measures, measures of physical impairment and measures of psychosocial factors should be used to monitor response to treatment. (v) Physical activity (that may include sport) is recommended for people with hip-related pain. (vi) Clinicians should discuss patient expectations, use shared-decision making and provide education. Recommendations for research were (i) Reporting of exercise programmes: Exercise descriptors such as load magnitude, number of repetitions and sets, duration of whole programme, duration of contractile element of exercise, duration of one repetition, time under tension, rest between repetitions, range of motion through which the exercise is performed, and rest between exercise sessions should be reported. (ii) Research should investigate the optimal frequency, intensity, time, type, volume and progression of exercise therapy. (iii) Research should examine the effect of patient education in people with hip-related pain. (iv) Research should investigate the effect of other treatments used in people with hip-related pain (for example: manual therapy, medications, injections). (v) Research should examine the impact of comorbidities and social determinants on treatment effectiveness in people with hip-related pain. Clinicians and researchers working with young to middle-aged active adults with hip-related pain may use these consensus recommendations to guide, develop, test and implement individualised, evidence-based physiotherapist-led rehabilitation programmes.
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4. |
- Mosler, Andrea Britt, et al.
(author)
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Standardised measurement of physical capacity in young and middle-aged active adults with hip-related pain : Recommendations from the first International Hip-related Pain Research Network (IHiPRN) meeting, Zurich, 2018
- 2020
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In: British journal of sports medicine. - : BMJ. - 0306-3674 .- 1473-0480. ; 54:12, s. 702-710
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Journal article (peer-reviewed)abstract
- Hip-related pain can significantly impact quality of life, function, work capacity, physical activity and family life. Standardised measurement methods of physical capacity of relevance to young and middle-aged active adults with hip-related pain are currently not established. The aim of this consensus paper was to provide recommendations for clinical practice and research on standardised measurement methods of physical capacity in young and middle-aged active adults with hip-related pain. Four areas of importance were identified: (1) clinical measures (range of motion, muscle strength, functional impairments), (2) laboratory-based measures (biomechanics and muscle function (muscle activity, size and adiposity)), (3) physical activity, and (4) return to sport/performance. The literature was reviewed, and a summary circulated to the working group to inform discussion at the consensus meeting. The working group developed clinical and research recommendations from the literature review, which were further discussed and modified within the working group at the consensus meeting. These recommendations were then presented to all 38 International Hip-related Pain Research Network (IHiPRN) participants for further discussion, refinement and consensus voting. Therefore, the recommendations voted on were based on a combination of current evidence and expert opinion. The consensus meeting voted on 13 recommendations, six of which were clinically orientated, and seven more research specific. We recommended that clinicians working with young and middle-aged active adults with hip-related pain assess strength using objective methods of measurement, and clinically assess performance of functional tasks, including walking and running. Physical activity should be quantified using both self-reported and objective measures, and patient expectations of recovery should be quantified prior to treatment. It was recommended that return to physical activity (including sport and occupation) be quantified, and sport-specific activities should be assessed prior to return to sport. The IHiPRN participants were uncertain regarding recommendations for range of motion assessment. Research recommendations were that the measurement properties of range of motion, strength and functional performance tests be investigated, reported and improved in both clinical and research settings. Reporting of movement-related parameters (biomechanics and muscle function) should be standardised and the relationship among movement-related parameters, symptoms, function, quality of life, and intra-articular and imaging findings should be investigated. Quantification of return to physical activity (including sport and occupational demands) is required in future research, and the return to sport continuum should be used. Future research is required to determine the best criteria for rehabilitation progression and return to physical activity following hip-related pain management.
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5. |
- Reiman, Michael P., et al.
(author)
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Consensus recommendations on the classification, definition and diagnostic criteria of hip-related pain in young and middle-aged active adults from the International Hip-related Pain Research Network, Zurich 2018
- 2020
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In: British journal of sports medicine. - : BMJ. - 0306-3674 .- 1473-0480. ; 54:11, s. 631-641
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Research review (peer-reviewed)abstract
- There is no agreement on how to classify, define or diagnose hip-related pain-a common cause of hip and groin pain in young and middle-aged active adults. This complicates the work of clinicians and researchers. The International Hip-related Pain Research Network consensus group met in November 2018 in Zurich aiming to make recommendations on how to classify, define and diagnose hip disease in young and middle-aged active adults with hip-related pain as the main symptom. Prior to the meeting we performed a scoping review of electronic databases in June 2018 to determine the definition, epidemiology and diagnosis of hip conditions in young and middle-aged active adults presenting with hip-related pain. We developed and presented evidence-based statements for these to a panel of 37 experts for discussion and consensus agreement. Both non-musculoskeletal and serious hip pathological conditions (eg, tumours, infections, stress fractures, slipped capital femoral epiphysis), as well as competing musculoskeletal conditions (eg, lumbar spine) should be excluded when diagnosing hip-related pain in young and middle-aged active adults. The most common hip conditions in young and middle-aged active adults presenting with hip-related pain are: (1) femoroacetabular impingement (FAI) syndrome, (2) acetabular dysplasia and/or hip instability and (3) other conditions without a distinct osseous morphology (labral, chondral and/or ligamentum teres conditions), and that these terms are used in research and clinical practice. Clinical examination and diagnostic imaging have limited diagnostic utility; a comprehensive approach is therefore essential. A negative flexion-adduction-internal rotation test helps rule out hip-related pain although its clinical utility is limited. Anteroposterior pelvis and lateral femoral head-neck radiographs are the initial diagnostic imaging of choice-advanced imaging should be performed only when requiring additional detail of bony or soft-tissue morphology (eg, for definitive diagnosis, research setting or when planning surgery). We recommend clear, detailed and consistent methodology of bony morphology outcome measures (definition, measurement and statistical reporting) in research. Future research on conditions with hip-related pain as the main symptom should include high-quality prospective studies on aetiology and prognosis. The most common hip conditions in active adults presenting with hip-related pain are: (1) FAI syndrome, (2) acetabular dysplasia and/or hip instability and (3) other conditions without distinct osseous morphology including labral, chondral and/or ligamentum teres conditions. The last category should not be confused with the incidental imaging findings of labral, chondral and/or ligamentum teres pathology in asymptomatic people. Future research should refine our current recommendations by determining the clinical utility of clinical examination and diagnostic imaging in prospective studies.
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7. |
- Ly, Monica T, et al.
(author)
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Association of Vascular Risk Factors and CSF and Imaging Biomarkers With White Matter Hyperintensities in Former American Football Players.
- 2024
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In: Neurology. - 1526-632X. ; 102:2
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Journal article (peer-reviewed)abstract
- Recent data link exposure to repetitive head impacts (RHIs) from American football with increased white matter hyperintensity (WMH) burden. WMH might have unique characteristics in the context of RHI beyond vascular risk and normal aging processes. We evaluated biological correlates of WMH in former American football players, including markers of amyloid, tau, inflammation, axonal injury, neurodegeneration, and vascular health.Participants underwent clinical interviews, MRI, and lumbar puncture as part of the Diagnostics, Imaging, and Genetics Network for the Objective Study and Evaluation of Chronic Traumatic Encephalopathy Research Project. Structural equation modeling tested direct and indirect effects between log-transformed total fluid-attenuated inversion recovery (FLAIR) lesion volumes (TLV) and the revised Framingham stroke risk profile (rFSRP), MRI-derived global metrics of cortical thickness and fractional anisotropy (FA), and CSF levels of amyloid β1-42, p-tau181, soluble triggering receptor expressed on myeloid cells 2 (sTREM2), and neurofilament light. Covariates included age, race, education, body mass index, APOE ε4 carrier status, and evaluation site. Models were performed separately for former football players and a control group of asymptomatic men unexposed to RHI.In 180 former football players (mean age = 57.2, 36% Black), higher log(TLV) had direct associations with the following: higher rFSRP score (B = 0.26, 95% CI 0.07-0.40), higher p-tau181 (B = 0.17, 95% CI 0.01-0.43), lower FA (B = -0.28, 95% CI -0.42 to -0.13), and reduced cortical thickness (B = -0.25, 95% CI -0.45 to -0.08). In 60 asymptomatic unexposed men (mean age = 59.3, 40% Black), there were no direct effects on log(TLV) (rFSRP: B = -0.03, 95% CI -0.48 to 0.57; p-tau181: B = -0.30, 95% CI -1.14 to 0.37; FA: B = -0.07, 95% CI -0.48 to 0.42; or cortical thickness: B = -0.28, 95% CI -0.64 to 0.10). The former football players showed stronger associations between log(TLV) and rFSRP (1,069% difference in estimates), p-tau181 (158%), and FA (287%) than the unexposed men.Risk factors and biological correlates of WMH differed between former American football players and asymptomatic unexposed men. In addition to vascular health, p-tau181 and diffusion tensor imaging indices of white matter integrity showed stronger associations with WMH in the former football players. FLAIR WMH may have specific risk factors and pathologic underpinnings in RHI-exposed individuals.
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8. |
- Wang, Li-San, et al.
(author)
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Rarity of the Alzheimer Disease-Protective APP A673T Variant in the United States.
- 2015
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In: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 72:2
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Journal article (peer-reviewed)abstract
- Recently, a rare variant in the amyloid precursor protein gene (APP) was described in a population from Iceland. This variant, in which alanine is replaced by threonine at position 673 (A673T), appears to protect against late-onset Alzheimer disease (AD). We evaluated the frequency of this variant in AD cases and cognitively normal controls to determine whether this variant will significantly contribute to risk assessment in individuals in the United States.
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9. |
- Arboleda-Velasquez, Joseph F, et al.
(author)
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Resistance to autosomal dominant Alzheimer's disease in an APOE3 Christchurch homozygote: a case report.
- 2019
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In: Nature medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 25:11, s. 1680-1683
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Journal article (peer-reviewed)abstract
- We identified a PSEN1 (presenilin 1) mutation carrier from the world's largest autosomal dominant Alzheimer's disease kindred, who did not develop mild cognitive impairment until her seventies, three decades after the expected age of clinical onset. The individual had two copies of the APOE3 Christchurch (R136S) mutation, unusually high brain amyloid levels and limited tau and neurodegenerative measurements. Our findings have implications for the role of APOE in the pathogenesis, treatment and prevention of Alzheimer's disease.
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10. |
- Burgi, Ciara R., et al.
(author)
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Which criteria are used to clear patients to return to sport after primary ACL reconstruction? A scoping review
- 2019
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In: British Journal of Sports Medicine. - : BMJ PUBLISHING GROUP. - 0306-3674 .- 1473-0480. ; 53:18, s. 1154-1161
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Research review (peer-reviewed)abstract
- Objective To describe the criteria used to clear athletes to return to sport (RTS) following primary ACL reconstruction. Design Scoping review. Data sources MEDLINE, Embase, CINAHL and SPORTDiscus electronic databases were searched using keywords related to ACL and RTS. Eligibility criteria Prospective or retrospective studies reporting at least one RTS criterion for athletes who had primary ACL reconstruction with an autograft. Results In total, 209 studies fulfilled the inclusion criteria. RTS criteria were categorised into six domains: time, strength, hop testing, clinical examination, patient-report and performance-based criteria. From the 209 included studies, time was used in 178 studies (85%), and in 88 studies (42%) was the sole RTS criterion. Strength tests were reported in 86 studies (41%). Sixteen different hop tests were used in 31 studies (15%). Clinical examination was used in 54 studies (26%), patient report in 26 studies (12%) and performance-based criteria in 41 studies (20%). Summary Time and impairment-based measures dominated RTS criteria, despite sport being a complex physical and biopsychosocial activity with demands across all aspects of function. Time was included as a criterion in 85% of studies, and over 80% of studies allowed RTS before 9 months. Whether RTS tests are valid-do they predict successful RTS?-is largely unknown.
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