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Sökning: WFRF:(Izquierdo E)

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  • Vigorito, Elena, et al. (författare)
  • Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers
  • 2016
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Population-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2 mutation carriers. Genotype data were available for 15,252 (2,462 ovarian cancer cases) BRCA1 and 8,211 (631 ovarian cancer cases) BRCA2 mutation carriers. Following genotype imputation, ovarian cancer associations were assessed for 4,873 and 5,020 SNPs in BRCA1 and BRCA2 mutation carriers respectively, within a retrospective cohort analytical framework. In BRCA1 mutation carriers one set of eight correlated candidate causal variants for ovarian cancer risk modification was identified (top SNP rs10124837, HR: 0.73, 95% CI: 0.68 to 0.79, p-value 2x 10-16). These variants were located up to 20 kb upstream of BNC2. In BRCA2 mutation carriers one region, up to 45 kb upstream of BNC2, and containing 100 correlated SNPs was identified as candidate causal (top SNP rs62543585, HR: 0.69, 95% CI: 0.59 to 0.80, p-value 1.0 x 10-6). The candidate causal in BRCA1 mutation carriers did not include the strongest associated variant at this locus in the general population. In sum, we identified a set of candidate causal variants in a region that encompasses the BNC2 transcription start site. The ovarian cancer association at 9p22.2 may be mediated by different variants in BRCA1 mutation carriers and in the general population. Thus, potentially different mechanisms may underlie ovarian cancer risk for mutation carriers and the general population.
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  • Barreto, Philipe de Souto, et al. (författare)
  • Recommendations on Physical Activity and Exercise for Older Adults Living in Long-Term Care Facilities : A Taskforce Report
  • 2016
  • Ingår i: Journal of the American Medical Directors Association. - : Elsevier BV. - 1525-8610 .- 1538-9375. ; 17:5, s. 381-392
  • Tidskriftsartikel (refereegranskat)abstract
    • A taskforce, under the auspices of The International Association of Gerontology and Geriatrics-Global Aging Research Network (IAGG-GARN) and the IAGG European Region Clinical Section, composed of experts from the fields of exercise science and geriatrics, met in Toulouse, in December 2015, with the aim of establishing recommendations of physical activity and exercise for older adults living in long-term care facilities (LTCFs). Due to the high heterogeneity in terms of functional ability and cognitive function that characterizes older adults living in LTCFs, taskforce members established 2 sets of recommendations: recommendations for reducing sedentary behaviors for all LTCF residents and recommendations for defining specific, evidence-based guidelines for exercise training for subgroups of LTCF residents. To promote a successful implementation of recommendations, taskforce experts highlighted the importance of promoting residents' motivation and pleasure, the key factors that can be increased when taking into account residents' desires, preferences, beliefs, and attitudes toward physical activity and exercise. The importance of organizational factors related to LTCFs and health care systems were recognized by the experts. In conclusion, this taskforce report proposes standards for the elaboration of strategies to increase physical activity as well as to prescribe exercise programs for older adults living in LTCFs. This report should be used as a guide for professionals working in LTCF settings.
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  • Caron, Jean-Bernard, et al. (författare)
  • The lower Cambrian Cranbrook Lagerstätte of British Columbia
  • 2024
  • Ingår i: Journal of the Geological Society. - : Geological Society of London. - 0016-7649 .- 2041-479X. ; 181:1
  • Forskningsöversikt (refereegranskat)abstract
    • Discovered over a century ago, the lower Cambrian (Series 2, Stage 4) Cranbrook Lagerstatte of southeastern British Columbia's Eager Formation is one of the oldest Burgess Shale-type deposits in North America. This Konservat-Lagerstatte is rich in olenelloid trilobites, but also yields a very low-diversity soft-bodied fossil assemblage including Tuzoia and Anomalocaris, and a low-diversity ichnofauna. Its scientific study, however, remains limited. A 2015 field-based investigation by the Royal Ontario Museum has revealed new information about the site's biota, depositional environment and taphonomic conditions. Not only is the Cranbrook Lagerstatte significant for early Cambrian biostratigraphy and comparisons with other Burgess Shale-type deposits, it also reveals some of the little-known diversity of life in a distal outer shelf environment during the Cambrian period.
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60.
  • Castro-González, A., et al. (författare)
  • The K2-OjOS Project*New and revisited planets and candidates in K2 campaigns 5, 16, & 18
  • 2022
  • Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 509:1, s. 1075-1095
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the first results of K2-OjOS, a collaborative project between professional and amateur astronomers primarily aimed to detect, characterize, and validate new extrasolar planets. For this work, 10 amateur astronomers looked for planetary signals by visually inspecting the 20 427 light curves of K2 campaign 18 (C18). They found 42 planet candidates, of which 18 are new detections and 24 had been detected in the overlapping C5 by previous works. We used archival photometric and spectroscopic observations, as well as new high-spatial resolution images in order to carry out a complete analysis of the candidates found, including a homogeneous characterization of the host stars, transit modelling, search for transit timing variations and statistical validation. As a result, we report four new planets (K2-355 b, K2-356 b, K2-357 b, and K2-358 b) and 14 planet candidates. Besides, we refine the transit ephemeris of the previously published planets and candidates by modelling C5, C16 (when available) and C18 photometric data jointly, largely improving the period and mid-transit time precision. Regarding individual systems, we highlight the new planet K2-356 b and candidate EPIC 211537087.02 being near a 2:1 period commensurability, the detection of significant TTVs in the bright star K2-184 (V = 10.35), the location of K2-103 b inside the habitable zone according to optimistic models, the detection of a new single transit in the known system K2-274, and the disposition reassignment of K2-120 b, which we consider as a planet candidate as the origin of the signal cannot be ascertained.
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61.
  • Gilbert, R. E., et al. (författare)
  • Trends in child maltreatment reply
  • 2012
  • Ingår i: The Lancet. - New York, USA : Elsevier. - 0140-6736 .- 1474-547X. ; 379:9831, s. 2049-2049
  • Tidskriftsartikel (refereegranskat)
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  • Kyriazis, Angelos, et al. (författare)
  • Dynamic ventilation He-3 MRI for the quantification of disease in the rat lung
  • 2012
  • Ingår i: IEEE Transactions on Biomedical Engineering. - 0018-9294 .- 1558-2531. ; 59, s. 777-786
  • Tidskriftsartikel (refereegranskat)abstract
    • Pulmonary diseases are known to be largely inhomogeneous. To evaluate such inhomogeneities, we are testing an image-based method to measure gas flow in the lung regionally. Dynamic, spin-density-weighted hyperpolarized He MR images performed during slow inhalation of this gas were analyzed to quantify regional inflation rate. This parameter was measured in regions of interest (ROIs) that were defined by a rectangular grid that covered the entire rat lung and grew dynamically with it during its inflation. We used regional inflation rate to quantify elastase-induced emphysema and to differentiate healthy ( n8) from elastase-treated ( n9) rat lungs as well as healthy from elastase-treated areas of one rat unilaterally treated with elastase in the left lung. Emphysema was also assessed by gold standard morphological and well-established hyperpolarized He MRI diffusion measurements. Mean values of regional inflation rates were significantly different for healthy and elastase-treated animals and correlated well with the apparent diffusion coefficient of He and morphological measurements. The image-based biomarker inflation rate may be useful for the assessment of regional lung ventilation. © 2011 IEEE.
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73.
  • Li, Zhijun, et al. (författare)
  • Multiobjective optimization for integrated tolerance allocation and fixture layout design in multistation assembly
  • 2006
  • Ingår i: Proceedings of the ASME International Design Engineering Technical Conferences and Computers and Information in Engineering Conference - 20. - New York : American Society of Mechanical Engineers. ; , s. 199-206
  • Konferensbidrag (refereegranskat)abstract
    • Cost and product quality are significant attributes in manufacturing processes, such as multistation assembly. We use multiobjective optimization for integrated tolerance allocation and fixture layout design to address their interaction and to quantify tradeoffs among cost, product quality, and assembly process robustness. Design decisions relate to product tolerances, assembly process tolerances, and fixture locating positions. A nested optimization strategy is adopted, and the proposed methodology is demonstrated using a vehicle side frame assembly example. The obtained results provide evidence for the existence of tradeoffs, based on which we can identify critical quality and budget requirements.
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74.
  • Li, Zhijun, et al. (författare)
  • Multiobjective Optimization for Integrated Tolerance Allocation and Fixture Layout Design in Multistation Assembly
  • 2008
  • Ingår i: Journal of manufacturing science and engineering. - : ASME International. - 1087-1357 .- 1528-8935. ; 130:4, s. 0445011-0445016
  • Tidskriftsartikel (refereegranskat)abstract
    • Cost and dimensional variation of products are significant attributes in multistation assembly processes. These attributes depend on product/process tolerances and fixture layouts. Typically, tolerance allocation and fixture layout design are conducted separately without considering potential interrelations. In this work, we use multiobjective optimization for integrated tolerance allocation and fixture layout design to address interactions and to quantify tradeoffs among cost, product variation, and assembly process sensitivity. A nested optimization strategy is applied to a vehicle side frame assembly. Results demonstrate the presence and quantification of tradeoffs, based on which we introduce the concept of critical variation and critical budget requirements
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75.
  • Lojewski, Tobias, et al. (författare)
  • The interplay of local electron correlations and ultrafast spin dynamics in fcc Ni
  • 2023
  • Ingår i: Materials Research Letters. - : Taylor & Francis. - 2166-3831. ; 11:8, s. 655-661
  • Tidskriftsartikel (refereegranskat)abstract
    • The complex electronic structure of metallic ferromagnets is determined by a balance between exchange interaction, electron hopping leading to band formation, and local Coulomb repulsion. By combining high energy and temporal resolution in femtosecond time-resolved X-ray absorption spectroscopy with ab initio time-dependent density functional theory we analyze the electronic structure in fcc Ni on the time scale of these interactions in a pump-probe experiment. We distinguish transient broadening and energy shifts in the absorption spectra, which we demonstrate to be captured by electron repopulation respectively correlation-induced modifications of the electronic structure, requiring to take the local Coulomb interaction into account.
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  • Martin-Izquierdo, M, et al. (författare)
  • Co-occurrence of cohesin complex and Ras signaling mutations during progression from myelodysplastic syndromes to secondary acute myeloid leukemia
  • 2021
  • Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 106:8, s. 2215-2223
  • Tidskriftsartikel (refereegranskat)abstract
    • Myelodysplastic syndromes (MDS) are hematological disorders at high risk of progression to secondary acute myeloid leukemia (sAML). However, the mutational dynamics and clonal evolution underlying disease progression are poorly understood at present. To elucidate the mutational dynamics of pathways and genes occurring during the evolution to sAML, next generation sequencing was performed on 84 serially paired samples of MDS patients who developed sAML (discovery cohort) and 14 paired samples from MDS patients who did not progress to sAML during follow-up (control cohort). Results were validated in an independent series of 388 MDS patients (validation cohort). We used an integrative analysis to identify how mutations, alone or in combination, contribute to leukemic transformation. The study showed that MDS progression to sAML is characterized by greater genomic instability and the presence of several types of mutational dynamics, highlighting increasing (STAG2) and newly-acquired (NRAS and FLT3) mutations. Moreover, we observed cooperation between genes involved in the cohesin and Ras pathways in 15-20% of MDS patients who evolved to sAML, as well as a high proportion of newly acquired or increasing mutations in the chromatin-modifier genes in MDS patients receiving a disease-modifying therapy before their progression to sAML.
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80.
  • Min, M, et al. (författare)
  • Silent lesions on MRI imaging - Shifting goal posts for treatment decisions in multiple sclerosis
  • 2018
  • Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 24:12, s. 1569-1577
  • Tidskriftsartikel (refereegranskat)abstract
    • The current best practice suggests yearly magnetic resonance imaging (MRI) to monitor treatment response in multiple sclerosis (MS) patients. Objective: To evaluate the current practice of clinicians changing MS treatment based on subclinical new MRI lesions alone. Methods: Using MSBase, an international MS patient registry with MRI data, we analysed the probability of treatment change among patients with clinically silent new MRI lesions. Results: A total of 8311 MRI brain scans of 4232 patients were identified. Around 26.9% (336/1247) MRIs with one new T2 lesion were followed by disease-modifying therapy (DMT) change, increasing to 50.2% (129/257) with six new T2 lesions. DMT change was twice as likely with new T1 contrast enhancing compared to new T2 lesions odds ratio (OR): 2.43, 95% confidence interval (CI): 2.00–2.96 vs OR: 1.26 (95% CI: 1.22–1.29). DMT change with new MRI lesions occurred most frequently with ‘injectable’ DMTs. The probability of switching therapy was greater only after high-efficacy therapies became available in 2007 (after, OR: 1.43, 95% CI: 1.28–1.59 vs before, OR: 0.98, 95% CI: 0.520–1.88). Conclusion: MS clinicians rely increasingly on MRI alone in their treatment decisions, utilizing low thresholds (1 new T2 lesion) for optimizing MS therapy. This signals a shift towards no evidence of disease activity (NEDA)-3 since high-efficacy therapies became available.
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81.
  • Oppewal, A, et al. (författare)
  • Correlates of Sedentary Behaviour in Adults with Intellectual Disabilities-A Systematic Review
  • 2018
  • Ingår i: International journal of environmental research and public health. - : MDPI AG. - 1660-4601. ; 15:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Individuals with intellectual disabilities (ID) are at high risk for high levels of sedentary behaviour. To inform the development of programmes to reduce sedentary behaviour, insight into the correlates is needed. Therefore, the aim of this study is to review the evidence on correlates of sedentary behaviour in adults with ID. We performed a systematic literature search in Ovid Medline, Ovid Embase, Web of Science and Google Scholar up to 19 January 2018, resulting in nine included studies that were published from 2011 to 2018. Correlates were categorized according to the ecological model. Studies predominantly focused on individual level correlates. Of those correlates studied in more than one study, having epilepsy was associated with less sedentary behaviour and inconsistent results were found for sex, genetic syndromes, weight status, physical health, mobility, level of ID, and mental health. Of the few interpersonal and environmental factors studied, only living arrangements were studied in more than one study, with inconsistent results. To date, we have limited and inconclusive evidence about correlates of sedentary behaviour in adults with ID. Only when future studies unravel correlates and determinants, across all domains of the ecological model, will the potential opportunities to improve health by reducing sedentary behaviour come within reach.
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86.
  • Prusakov, Pavel, et al. (författare)
  • A global point prevalence survey of antimicrobial use in neonatal intensive care units : The no-more-antibiotics and resistance (NO-MAS-R) study
  • 2021
  • Ingår i: eClinicalMedicine. - : Elsevier. - 2589-5370. ; 32
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Global assessment of antimicrobial agents prescribed to infants in the neonatal intensive care unit (NICU) may inform antimicrobial stewardship efforts.Methods: We conducted a one-day global point prevalence study of all antimicrobials provided to NICU infants. Demographic, clinical, and microbiologic data were obtained including NICU level, census, birth weight, gestational/chronologic age, diagnoses, antimicrobial therapy (reason for use; length of therapy), antimicrobial stewardship program (ASP), and 30-day in-hospital mortality.Findings: On July 1, 2019, 26% of infants (580/2,265; range, 0-100%; median gestational age, 33 weeks; median birth weight, 1800 g) in 84 NICUs (51, high-income; 33, low-to-middle income) from 29 countries (14, high-income; 15, low-to-middle income) in five continents received >= 1 antimicrobial agent (92%, antibacterial; 19%, antifungal; 4%, antiviral). The most common reasons for antibiotic therapy were "rule-out" sepsis (32%) and "culture-negative" sepsis (16%) with ampicillin (40%), gentamicin (35%), amikacin (19%), vancomycin (15%), and meropenem (9%) used most frequently. For definitive treatment of presumed/confirmed infection, vancomycin (26%), amikacin (20%), and meropenem (16%) were the most prescribed agents. Length of therapy for culture-positive and "culture-negative" infections was 12 days (median; IQR, 8-14) and 7 days (median; IQR, 5-10), respectively. Mortality was 6% (42%, infection-related). An NICU ASP was associated with lower rate of antibiotic utilization (p = 0.02).Interpretation: Global NICU antibiotic use was frequent and prolonged regardless of culture results. NICU-specific ASPs were associated with lower antibiotic utilization rates, suggesting the need for their implementation worldwide.
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  • Zurcher, N. R., et al. (författare)
  • C-11 PBR28 MR-PET imaging reveals lower regional brain expression of translocator protein (TSPO) in young adult males with autism spectrum disorder
  • 2021
  • Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578.
  • Tidskriftsartikel (refereegranskat)abstract
    • Mechanisms of neuroimmune and mitochondrial dysfunction have been repeatedly implicated in autism spectrum disorder (ASD). To examine these mechanisms in ASD individuals, we measured the in vivo expression of the 18 kDa translocator protein (TSPO), an activated glial marker expressed on mitochondrial membranes. Participants underwent scanning on a simultaneous magnetic resonance-positron emission tomography (MR-PET) scanner with the second-generation TSPO radiotracer [C-11]PBR28. By comparing TSPO in 15 young adult males with ASD with 18 age- and sex-matched controls, we showed that individuals with ASD exhibited lower regional TSPO expression in several brain regions, including the bilateral insular cortex, bilateral precuneus/posterior cingulate cortex, and bilateral temporal, angular, and supramarginal gyri, which have previously been implicated in autism in functional MR imaging studies. No brain region exhibited higher regional TSPO expression in the ASD group compared with the control group. A subset of participants underwent a second MR-PET scan after a median interscan interval of 3.6 months, and we determined that TSPO expression over this period of time was stable and replicable. Furthermore, voxelwise analysis confirmed lower regional TSPO expression in ASD at this later time point. Lower TSPO expression in ASD could reflect abnormalities in neuroimmune processes or mitochondrial dysfunction.
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