| 461. |
- Kuldkepp, Matias, et al.
(författare)
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Motional Stark effect diagnostic pilot experiment for MAST
- 2006
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Ingår i: Review of Scientific Instruments. - : AIP Publishing. - 0034-6748 .- 1089-7623. ; 77:10, s. 10E905-
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Tidskriftsartikel (refereegranskat)abstract
- Exploiting the motional Stark effect (MSE) in the low magnetic fields of spherical tokamaks such as MAST is complicated by the Doppler smearing of the relatively closely spaced Stark components. Extensive modeling of MSE spectra and the subsequent polarized fraction (similar to 20%) of spectrally filtered light and signal to noice ratios have been performed taking account of real experimental conditions including neutral beam parameters, port sizes, optical losses, filter characteristics, etc. A design is selected which uses high throughput interference filters (0.1 nm bandpass ) for separation of the spectral components. An accuracy of similar to 0.5 degrees S compared with typically 15 degrees is estimated for field angle measurements. The design allows for early implementation, starting with a pilot two chord system, and for an economic expansion to a multiplicity of chords. Matching the Doppler shifted D-alpha from the beam neutrals will be accomplished by a combination of filter selection and fine-tuning of the beam voltage. Avoiding filter tuning in the design greatly simplifies the diagnostic. Calibration results of the diagnostic support the calculations.
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| 462. |
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| 463. |
- Lahrouchi, Najim, et al.
(författare)
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Transethnic Genome-Wide Association Study Provides Insights in the Genetic Architecture and Heritability of Long QT Syndrome
- 2020
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Ingår i: Circulation. - : Lippincott Williams & Wilkins. - 0009-7322 .- 1524-4539. ; 142:4, s. 324-338
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Tidskriftsartikel (refereegranskat)abstract
- Background: Long QT syndrome (LQTS) is a rare genetic disorder and a major preventable cause of sudden cardiac death in the young. A causal rare genetic variant with large effect size is identified in up to 80% of probands (genotype positive) and cascade family screening shows incomplete penetrance of genetic variants. Furthermore, a proportion of cases meeting diagnostic criteria for LQTS remain genetically elusive despite genetic testing of established genes (genotype negative). These observations raise the possibility that common genetic variants with small effect size contribute to the clinical picture of LQTS. This study aimed to characterize and quantify the contribution of common genetic variation to LQTS disease susceptibility. Methods: We conducted genome-wide association studies followed by transethnic meta-analysis in 1656 unrelated patients with LQTS of European or Japanese ancestry and 9890 controls to identify susceptibility single nucleotide polymorphisms. We estimated the common variant heritability of LQTS and tested the genetic correlation between LQTS susceptibility and other cardiac traits. Furthermore, we tested the aggregate effect of the 68 single nucleotide polymorphisms previously associated with the QT-interval in the general population using a polygenic risk score. Results: Genome-wide association analysis identified 3 loci associated with LQTS at genome-wide statistical significance (P<5x10(-8)) nearNOS1AP,KCNQ1, andKLF12, and 1 missense variant inKCNE1(p.Asp85Asn) at the suggestive threshold (P<10(-6)). Heritability analyses showed that approximate to 15% of variance in overall LQTS susceptibility was attributable to common genetic variation (h2SNP0.148; standard error 0.019). LQTS susceptibility showed a strong genome-wide genetic correlation with the QT-interval in the general population (r(g)=0.40;P=3.2x10(-3)). The polygenic risk score comprising common variants previously associated with the QT-interval in the general population was greater in LQTS cases compared with controls (P<10-13), and it is notable that, among patients with LQTS, this polygenic risk score was greater in patients who were genotype negative compared with those who were genotype positive (P<0.005). Conclusions: This work establishes an important role for common genetic variation in susceptibility to LQTS. We demonstrate overlap between genetic control of the QT-interval in the general population and genetic factors contributing to LQTS susceptibility. Using polygenic risk score analyses aggregating common genetic variants that modulate the QT-interval in the general population, we provide evidence for a polygenic architecture in genotype negative LQTS.
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| 464. |
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| 465. |
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| 466. |
- Lawlor, B., et al.
(författare)
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Nilvadipine in mild to moderate Alzheimer disease: A randomised controlled trial
- 2018
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Ingår i: Plos Medicine. - : Public Library of Science (PLoS). - 1549-1676. ; 15:9
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Tidskriftsartikel (refereegranskat)abstract
- Background This study reports the findings of the first large-scale Phase III investigator-driven clinical trial to slow the rate of cognitive decline in Alzheimer disease with a dihydropyridine (DHP) calcium channel blocker, nilvadipine. Nilvadipine, licensed to treat hypertension, reduces amyloid production, increases regional cerebral blood flow, and has demonstrated antiinflammatory and anti-tau activity in preclinical studies, properties that could have diseasemodifying effects for Alzheimer disease. We aimed to determine if nilvadipine was effective in slowing cognitive decline in subjects with mild to moderate Alzheimer disease. NILVAD was an 18-month, randomised, placebo-controlled, double-blind trial that randomised participants between 15 May 2013 and 13 April 2015. The study was conducted at 23 academic centres in nine European countries. Of 577 participants screened, 511 were eligible and were randomised (258 to placebo, 253 to nilvadipine). Participants took a trial treatment capsule once a day after breakfast for 78 weeks. Participants were aged > 50 years, meeting National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's disease Criteria (NINCDS-ADRDA) for diagnosis of probable Alzheimer disease, with a Standardised Mini-Mental State Examination (SMMSE) score of >= 12 and < 27. Participants were randomly assigned to 8 mg sustained-release nilvadipine or matched placebo. The a priori defined primary outcome was progression on the Alzheimer's Disease Assessment Scale Cognitive Subscale-12 (ADAS-Cog 12) in the modified intention-to-treat (mITT) population (n = 498), with the Clinical Dementia Rating Scale sum of boxes (CDR-sb) as a gated co-primary outcome, eligible to be promoted to primary end point conditional on a significant effect on the ADAS-Cog 12. The analysis set had a mean age of 73 years and was 62% female. Baseline demographic and Alzheimer disease +/- specific characteristics were similar between treatment groups, with reported mean of 1.7 years since diagnosis and mean SMMSE of 20.4. The prespecified primary analyses failed to show any treatment benefit for nilvadipine on the co-primary outcome (p = 0.465). Decline from baseline in ADASCog 12 on placebo was 0.79 (95% CI, -0.07 +/- 1.64) at 13 weeks, 6.41 (5.33 +/- 7.49) at 52 weeks, and 9.63 (8.33 +/- 10.93) at 78 weeks and on nilvadipine was 0.88 (0.02 +/- 1.74) at 13 weeks, 5.75 (4.66 +/- 6.85) at 52 weeks, and 9.41 (8.09 +/- 10.73) at 78 weeks. Exploratory analyses of the planned secondary outcomes showed no substantial effects, including on the CDR-sb or the Disability Assessment for Dementia. Nilvadipine appeared to be safe and well tolerated. Mortality was similar between groups (3 on nilvadipine, 4 on placebo); higher counts of adverse events (AEs) on nilvadipine (1,129 versus 1,030), and serious adverse events (SAEs; 146 versus 101), were observed. There were 14 withdrawals because of AEs. Major limitations of this study were that subjects had established dementia and the likelihood that non-Alzheimer subjects were included because of the lack of biomarker confirmation of the presence of brain amyloid. The results do not suggest benefit of nilvadipine as a treatment in a population spanning mild to moderate Alzheimer disease.
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| 467. |
- Lawson, C., et al.
(författare)
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Development of an international comorbidity education framework
- 2017
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Ingår i: Nurse Education Today. - : CHURCHILL LIVINGSTONE. - 0260-6917 .- 1532-2793. ; 55, s. 82-89
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Tidskriftsartikel (refereegranskat)abstract
- Context The increasing number of people living with multiple chronic conditions in addition to an index condition has become an international healthcare priority. Health education curricula have been developed alongside single condition frameworks in health service policy and practice and need redesigning to incorporate optimal management of multiple conditions. Aim: Our aims were to evaluate current teaching and learning about comorbidity care amongst the global population of healthcare students from different disciplines and to develop an International Comorbidity Education Framework (ICEF) for incorporating comorbidity concepts into health education. Methods: We surveyed nursing, medical and pharmacy students from England, India, Italy and Sweden to evaluate their understanding of comorbidity care. A list of core comorbidity content was constructed by an international group of higher education academics and clinicians from the same disciplines, by searching current curricula and analysing clinical frameworks and the student survey data. This list was used to develop the International Comorbidity Education Framework. Results: The survey sample consisted of 917 students from England (42%), India (48%), Italy (8%) and Sweden (2%). The majority of students across all disciplines said that they lacked knowledge, training and confidence in comorbidity care and were unable to identify specific teaching on comorbidities. All student groups wanted further comorbidity training. The health education institution representatives found no specific references to comorbidity in current health education curricula. Current clinical frameworks were used to develop an agreed list of core comorbidity content and hence an International Comorbidity Education Framework. Conclusions: Based on consultation with academics and clinicians and on student feedback we developed an International Comorbidity Education Framework to promote the integration of comorbidity concepts into current healthcare curricula.
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| 468. |
- Levitis, E, et al.
(författare)
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Centering inclusivity in the design of online conferences-An OHBM-Open Science perspective
- 2021
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Ingår i: GigaScience. - : Oxford University Press (OUP). - 2047-217X. ; 10:8
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Tidskriftsartikel (refereegranskat)abstract
- As the global health crisis unfolded, many academic conferences moved online in 2020. This move has been hailed as a positive step towards inclusivity in its attenuation of economic, physical, and legal barriers and effectively enabled many individuals from groups that have traditionally been underrepresented to join and participate. A number of studies have outlined how moving online made it possible to gather a more global community and has increased opportunities for individuals with various constraints, e.g., caregiving responsibilities.Yet, the mere existence of online conferences is no guarantee that everyone can attend and participate meaningfully. In fact, many elements of an online conference are still significant barriers to truly diverse participation: the tools used can be inaccessible for some individuals; the scheduling choices can favour some geographical locations; the set-up of the conference can provide more visibility to well-established researchers and reduce opportunities for early-career researchers. While acknowledging the benefits of an online setting, especially for individuals who have traditionally been underrepresented or excluded, we recognize that fostering social justice requires inclusivity to actively be centered in every aspect of online conference design.Here, we draw from the literature and from our own experiences to identify practices that purposefully encourage a diverse community to attend, participate in, and lead online conferences. Reflecting on how to design more inclusive online events is especially important as multiple scientific organizations have announced that they will continue offering an online version of their event when in-person conferences can resume.
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