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2.
  • Dima, Danai, et al. (författare)
  • Subcortical volumes across the lifespan : Data from 18,605 healthy individuals aged 3-90 years.
  • 2022
  • Ingår i: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 43:1, s. 452-469
  • Tidskriftsartikel (refereegranskat)abstract
    • Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.
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3.
  • Frangou, Sophia, et al. (författare)
  • Cortical thickness across the lifespan : Data from 17,075 healthy individuals aged 3-90 years
  • 2022
  • Ingår i: Human Brain Mapping. - : John Wiley & Sons. - 1065-9471 .- 1097-0193. ; 43:1, s. 431-451
  • Tidskriftsartikel (refereegranskat)abstract
    • Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3-90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes.
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4.
  • Wierenga, Lara M., et al. (författare)
  • Greater male than female variability in regional brain structure across the lifespan
  • 2022
  • Ingår i: Human Brain Mapping. - : John Wiley & Sons. - 1065-9471 .- 1097-0193. ; 43:1, s. 470-499
  • Tidskriftsartikel (refereegranskat)abstract
    • For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.
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5.
  • Abazajian, Kevork, et al. (författare)
  • CMB-S4 : Forecasting Constraints on Primordial Gravitational Waves
  • 2022
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 926:1
  • Tidskriftsartikel (refereegranskat)abstract
    • CMB-S4—the next-generation ground-based cosmic microwave background (CMB) experiment—is set to significantly advance the sensitivity of CMB measurements and enhance our understanding of the origin and evolution of the universe. Among the science cases pursued with CMB-S4, the quest for detecting primordial gravitational waves is a central driver of the experimental design. This work details the development of a forecasting framework that includes a power-spectrum-based semianalytic projection tool, targeted explicitly toward optimizing constraints on the tensor-to-scalar ratio, r, in the presence of Galactic foregrounds and gravitational lensing of the CMB. This framework is unique in its direct use of information from the achieved performance of current Stage 2–3 CMB experiments to robustly forecast the science reach of upcoming CMB-polarization endeavors. The methodology allows for rapid iteration over experimental configurations and offers a flexible way to optimize the design of future experiments, given a desired scientific goal. To form a closed-loop process, we couple this semianalytic tool with map-based validation studies, which allow for the injection of additional complexity and verification of our forecasts with several independent analysis methods. We document multiple rounds of forecasts for CMB-S4 using this process and the resulting establishment of the current reference design of the primordial gravitational-wave component of the Stage-4 experiment, optimized to achieve our science goals of detecting primordial gravitational waves for r > 0.003 at greater than 5σ, or in the absence of a detection, of reaching an upper limit of r < 0.001 at 95% CL.
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6.
  • Klug, Stefanie J, et al. (författare)
  • TP53 codon 72 polymorphism and cervical cancer : a pooled analysis of individual data from 49 studies
  • 2009
  • Ingår i: The Lancet Oncology. - 1470-2045 .- 1474-5488. ; 10:8, s. 772-784
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Cervical cancer is caused primarily by human papillomaviruses (HPV). The polymorphism rs1042522 at codon 72 of the TP53 tumour-suppressor gene has been investigated as a genetic cofactor. More than 80 studies were done between 1998 and 2006, after it was initially reported that women who are homozygous for the arginine allele had a risk for cervical cancer seven times higher than women who were heterozygous for the allele. However, results have been inconsistent. Here we analyse pooled data from 49 studies to determine whether there is an association between TP53 codon 72 polymorphism and cervical cancer. METHODS: Individual data on 7946 cases and 7888 controls from 49 different studies worldwide were reanalysed. Odds ratios (OR) were estimated using logistic regression, stratifying by study and ethnic origin. Subgroup analyses were done for infection with HPV, ethnic origin, Hardy-Weinberg equilibrium, study quality, and the material used to determine TP53 genotype. FINDINGS: The pooled estimates (OR) for invasive cervical cancer were 1.22 (95% CI 1.08-1.39) for arginine homozygotes compared with heterozygotes, and 1.13 (0.94-1.35) for arginine homozygotes versus proline homozygotes. Subgroup analyses showed significant excess risks only in studies where controls were not in Hardy-Weinberg equilibrium (1.71 [1.21-2.42] for arginine homozygotes compared with heterozygotes), in non-epidemiological studies (1.35 [1.15-1.58] for arginine homozygotes compared with heterozygotes), and in studies where TP53 genotype was determined from tumour tissue (1.39 [1.13-1.73] for arginine homozygotes compared with heterozygotes). Null results were noted in studies with sound epidemiological design and conduct (1.06 [0.87-1.29] for arginine homozygotes compared with heterozygotes), and studies in which TP53 genotype was determined from white blood cells (1.06 [0.87-1.29] for arginine homozygotes compared with heterozygotes). INTERPRETATION: Subgroup analyses indicated that excess risks were most likely not due to clinical or biological factors, but to errors in study methods. No association was found between cervical cancer and TP53 codon 72 polymorphism when the analysis was restricted to methodologically sound studies.
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7.
  • Scull, Margaret A, et al. (författare)
  • Hepatitis C virus infects rhesus macaque hepatocytes and simianized mice.
  • 2015
  • Ingår i: Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 0270-9139 .- 1527-3350. ; 62:1, s. 57-67
  • Tidskriftsartikel (refereegranskat)abstract
    • UNLABELLED: At least 170 million people are chronically infected with hepatitis C virus (HCV). Owing to the narrow host range of HCV and restricted use of chimpanzees, there is currently no suitable animal model for HCV pathogenesis studies or the development of a HCV vaccine. To identify cellular determinants of interspecies transmission and establish a novel immunocompetent model system, we examined the ability of HCV to infect hepatocytes from a small nonhuman primate, the rhesus macaque (Macaca mulatta). We show that the rhesus orthologs of critical HCV entry factors support viral glycoprotein-dependent virion uptake. Primary hepatocytes from rhesus macaques are also permissive for HCV-RNA replication and particle production, which is enhanced when antiviral signaling is suppressed. We demonstrate that this may be owing to the diminished capacity of HCV to antagonize mitochondrial antiviral-signaling protein-dependent innate cellular defenses. To test the ability of HCV to establish persistent replication in vivo, we engrafted primary rhesus macaque hepatocytes into immunocompromised xenorecipients. Inoculation of resulting simian liver chimeric mice with either HCV genotype 1a or 2a resulted in HCV serum viremia for up to 10 weeks.CONCLUSION: Together, these data indicate that rhesus macaques may be a viable model for HCV and implicate host immunity as a potential species-specific barrier to HCV infection. We conclude that suppression of host immunity or further viral adaptation may allow robust HCV infection in rhesus macaques and creation of a new animal model for studies of HCV pathogenesis, lentivirus coinfection, and vaccine development.
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9.
  • Kaplan, Lew, et al. (författare)
  • Retinal regions shape human and murine Müller cell proteome profile and functionality
  • 2023
  • Ingår i: GLIA. - : Wiley. - 0894-1491 .- 1098-1136. ; 71:2, s. 391-414
  • Tidskriftsartikel (refereegranskat)abstract
    • The human macula is a highly specialized retinal region with pit-like morphology and rich in cones. How Müller cells, the principal glial cell type in the retina, are adapted to this environment is still poorly understood. We compared proteomic data from cone- and rod-rich retinae from human and mice and identified different expression profiles of cone- and rod-associated Müller cells that converged on pathways representing extracellular matrix and cell adhesion. In particular, epiplakin (EPPK1), which is thought to play a role in intermediate filament organization, was highly expressed in macular Müller cells. Furthermore, EPPK1 knockout in a human Müller cell-derived cell line led to a decrease in traction forces as well as to changes in cell size, shape, and filopodia characteristics. We here identified EPPK1 as a central molecular player in the region-specific architecture of the human retina, which likely enables specific functions under the immense mechanical loads in vivo.
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10.
  • Koletzko, Berthold, et al. (författare)
  • Should formula for infants provide arachidonic acid along with DHA? : A position paper of the European Academy of Paediatrics and the Child Health Foundation
  • 2020
  • Ingår i: American Journal of Clinical Nutrition. - : OXFORD UNIV PRESS. - 0002-9165 .- 1938-3207. ; 111:1, s. 10-16
  • Tidskriftsartikel (refereegranskat)abstract
    • Recently adopted regulatory standards on infant and follow-on formula for the European Union stipulate that from February 2020 onwards, all such products marketed in the European Union must contain 20-50 mg omega-3 DHA (22:6n-3) per 100 kcal, which is equivalent to about 0.5-1% of fatty acids (FAs) and thus higher than typically found in human milk and current infant formula products, without the need to also include co-6 arachidonic acid (AA; 20:4n-6). This novel concept of infant formula composition has given rise to concern and controversy because there is no accountable evidence on its suitability and safety in healthy infants. Therefore, international experts in the field of infant nutrition were invited to review the state of scientific research on DHA and AA, and to discuss the questions arising from the new European regulatory standards. Based on the available information, we recommend that infant and follow-on formula should provide both DHA and AA. The DHA should equal at least the mean content in human milk globally (0.3% of FAs) but preferably reach 0.5% of FAs. Although optimal AA intake amounts remain to be defined, we strongly recommend that AA should be provided along with DHA. At amounts of DHA in infant formula up to similar to 0.64%, AA contents should at least equal the DHA contents. Further well-designed clinical studies should evaluate the optimal intakes of DHA and AA in infants at different ages based on relevant outcomes.
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11.
  • Lang, Angelica E., et al. (författare)
  • A randomized controlled trial investigating effects of an individualized pedometer driven walking program on chronic low back pain
  • 2021
  • Ingår i: BMC Musculoskeletal Disorders. - : Springer Nature. - 1471-2474. ; 22:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Walking is an easily prescribed physical activity for people with low back pain (LBP). However, the evidence for its effectiveness to improve pain and disability levels for people with chronic low back pain (CLBP) within a community setting has not been evaluated. This study evaluates the effectiveness of a clinician guided, pedometer-driven, walking intervention for increasing physical activity and improving clinical outcomes compared to education and advice. Methods: Randomized controlled trial recruiting N = 174 adults with CLBP. Participants were randomly allocated into either a standardized care group (SG) or pedometer based walking group (WG) using minimization allocation with a 2:1 ratio to the WG. Prior to randomization all participants were given a standard package of education and advice regarding self-management and the benefits of staying active. Following randomization the WG undertook a physiotherapist guided pedometer-driven walking program for 12 weeks. This was individually tailored by weekly negotiation of daily step targets. Main outcome was the Oswestry Disability Index (ODI) recorded at baseline, 12 weeks, 6 and 12 months. Other outcomes included, numeric pain rating, International Physical Activity Questionnaire (IPAQ), Fear-Avoidance Beliefs Questionnaire (FABQ), Back Beliefs questionnaire (BBQ), Physical Activity Self-efficacy Scale, and EQ-5D-5L quality of life estimate. Results: N = 138 (79%) participants completed all outcome measures at 12 weeks reducing to N = 96 (55%) at 12 months. Both observed and intention to treat analysis did not show any statistically significant difference in ODI change score between the WG and the SG at all post-intervention time points. There were also no significant between group differences for change scores in all secondary outcome measures. Post hoc sensitivity analyses revealed moderately disabled participants (baseline ODI >= 21.0) demonstrated a greater reduction in mean ODI scores at 12 months in the WG compared to SG, while WG participants with a daily baseline step count < 7500 steps demonstrated a greater reduction in mean ODI scores at 12 weeks. Conclusions: Overall, we found no significant difference in change of levels of (ODI) disability between the SG and WG following the walking intervention. However, ODI responses to a walking program for those with moderate levels of baseline disability and those with low baseline step count offer a potential future focus for continued research into the benefit of walking as a management strategy for chronic LBP. Trial registration: United States National Institutes of Health Clinical Trails registry (http://ClinicalTrials.gov/) No. NCT02284958 (27/10/2014).
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12.
  • Lazaridis, Iosif, et al. (författare)
  • Ancient human genomes suggest three ancestral populations for present-day Europeans
  • 2014
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 513:7518, s. 409-
  • Tidskriftsartikel (refereegranskat)abstract
    • We sequenced the genomes of a similar to 7,000-year-old farmer from Germany and eight similar to 8,000-year-old hunter-gatherers from Luxembourg and Sweden. We analysed these and other ancient genomes(1-4) with 2,345 contemporary humans to show that most present-day Europeans derive from at least three highly differentiated populations: west European hunter-gatherers, who contributed ancestry to all Europeans but not to Near Easterners; ancient north Eurasians related to Upper Palaeolithic Siberians(3), who contributed to both Europeans and Near Easterners; and early European farmers, who were mainly of Near Eastern origin but also harboured west European hunter-gatherer related ancestry. We model these populations' deep relationships and show that early European farmers had similar to 44% ancestry from a 'basal Eurasian' population that split before the diversification of other non-African lineages.
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13.
  • Perley, Daniel A., et al. (författare)
  • The fast, luminous ultraviolet transient AT2018cow : extreme supernova, or disruption of a star by an intermediate-mass black hole?
  • 2019
  • Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 484:1, s. 1031-1049
  • Tidskriftsartikel (refereegranskat)abstract
    • Wide-field optical surveys have begun to uncover large samples of fast (t(rise) less than or similar to 5 d), luminous (M-peak < 18), blue transients. While commonly attributed to the breakout of a supernova shock into a dense wind, the great distances to the transients of this class found so far have hampered detailed investigation of their properties. We present photometry and spectroscopy from a comprehensive worldwide campaign to observe AT 2018cow (ATLAS 18qqn), the first fast-luminous optical transient to be found in real time at low redshift. Our first spectra (<2 days after discovery) are entirely featureless. A very broad absorption feature suggestive of near-relativistic velocities develops between 3 and 8 days, then disappears. Broad emission features of H and He develop after >10 days. The spectrum remains extremely hot throughout its evolution, and the photospheric radius contracts with time (receding below R < 10 (14) cm after 1 month). This behaviour does not match that of any known supernova, although a relativistic jet within a fallback supernova could explain some of the observed features. Alternatively, the transient could originate from the disruption of a star by an intermediate-mass black hole, although this would require long-lasting emission of highly super-Eddington thermal radiation. In either case, AT 2018cow suggests that the population of fast luminous transients represents a new class of astrophysical event. Intensive follow-up of this event in its late phases, and of any future events found at comparable distance, will be essential to better constrain their origins.
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14.
  • Reist, Robyn M., et al. (författare)
  • Ergonomic assessment of veterinarians during performance of bovine reproductive examinations
  • 2021
  • Ingår i: Journal of the American Veterinary Medical Associtation. - : American Veterinary Medical Association. - 0003-1488 .- 1943-569X. ; 258:11, s. 1243-1253
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE To identify and quantify potential ergonomic hazards associated with routine reproductive examinations of cattle. SAMPLE 7 bovine veterinarians. PROCEDURES Each veterinarian was observed and videotaped during 2 bovine reproductive examination appointments. During each appointment, a force-matching protocol was used to estimate the entry force used by the veterinarian to insert an arm into a cow's rectum. Veterinarian posture and repetitive movements and the work environment were assessed and quantified during review of the video recordings. Descriptive data were generated. RESULTS Of the 14 appointments observed, 9 and 5 involved examination of beef and dairy cows, respectively. For all veterinarians, an arm inclination >= 60 degrees was observed during most reproductive examinations. The number of examinations performed per hour ranged from 19.1 to 116.8. The estimated entry force ranged from 121 to 349 N. During all 9 appointments involving beef cows, the veterinarian participated in other tasks (eg, operating overhead levers, opening gates, or assisting with cattle handling) that represented ergonomic hazards. CONCLUSIONS AND CLINICAL RELEVANCE Results confirmed that reproductive examination of cattle exposes veterinarians to various ergonomic hazards involving awkward positions and repetitive and forceful exertions that can contribute to musculoskeletal discomfort and injury, particularly of the upper extremities (neck, shoulders, upper back, arms, elbows, wrists, and hands). Veterinarians frequently participated in other tasks during reproductive examination appointments that exposed them to additional ergonomic hazards. Risk mitigation strategies should prioritize minimizing exposure of veterinarians to tasks not directly associated with the reproductive examination procedure to decrease their overall ergonomic hazard burden.
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15.
  • Reist, Robyn M., et al. (författare)
  • Risk factors associated with work-preventing musculoskeletal discomfort in the upper extremities of bovine practitioners
  • 2020
  • Ingår i: Journal of the American Veterinary Medical Associtation. - : American Veterinary Medical Association. - 0003-1488 .- 1943-569X. ; 257:4, s. 410-416
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE To identify risk factors associated with work-preventing musculoskeletal discomfort (MSKD) in the upper extremities (defined as neck, shoulders, upper back, arms, elbows, wrists, and hands) of bovine practitioners. SAMPLE 116 members of the Western Canadian Association of Bovine Practitioners. PROCEDURES Data from a previously described cross-sectional survey of western Canadian bovine practitioners underwent further analysis. The survey, developed to glean information about MSKD in bovine practitioners, was a modified standardized Nordic questionnaire that included questions regarding personal and work characteristics and incidence and location of MSKD during the preceding 12 months along with perceptions about most physically demanding tasks. Logistic regression was used to identify factors associated with work-preventing upper extremity MSKD. RESULTS 18 of 116 (15.5%) respondents indicated they had experienced work-preventing upper extremity MSKD during the preceding 12 months. The final multivariable regression model indicated that practice type (mixed animal vs primarily [> 50%] bovine; OR, 3.20; 95% CI, 0.96 to 10.67), practitioner height (OR, 0.93; 95% CI, 0.87 to 0.99), and number of veterinarians in the practice (OR, 1.32; 95% CI, 1.05 to 1.66) were significantly associated with the odds of work-preventing upper extremity MSKD. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that reproductive examination of cattle was not a significant risk factor for upper extremity MSKD in bovine practitioners. Further research into the effects of biomechanical, organizational, and psychosocial workplace factors on the development of MSKD in bovine practitioners is necessary to help inform prevention strategies to foster career longevity in this increasingly diverse practitioner group.
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17.
  • Ascenzi, Stefano, et al. (författare)
  • A luminosity distribution for kilonovae based on short gamma-ray burst afterglows
  • 2019
  • Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 486:1, s. 672-690
  • Tidskriftsartikel (refereegranskat)abstract
    • The combined detection of a gravitational-wave signal, kilonova, and short gamma-ray burst (sGRB) from GW170817 marked a scientific breakthrough in the field of multimessenger astronomy. But even before GW170817, there have been a number of sGRBs with possible associated kilonova detections. In this work, we re-examine these ` historical' sGRB afterglows with a combination of state-of-the-art afterglow and kilonova models. This allows us to include optical/near-infrared synchrotron emission produced by the sGRB as well as ultraviolet/optical/near-infrared emission powered by the radioactive decay of r-process elements (i.e. the kilonova). Fitting the light curves, we derive the velocity and the mass distribution as well as the composition of the ejected material. The posteriors on kilonova parameters obtained from the fit were turned into distributions for the peak magnitude of the kilonova emission in different bands and the time at which this peak occurs. From the sGRB with an associated kilonova, we found that the peak magnitude in H bands falls in the range [-16.2, -13.1] (95 per cent of confidence) and occurs within 0.8-3.6 d after the sGRB prompt emission. In g band instead we obtain a peak magnitude in range [-16.8, -12.3] occurring within the first 18 h after the sGRB prompt. From the luminosity distributions of GW170817/AT2017gfo, kilonova candidates GRB130603B, GRB050709, and GRB060614 (with the possible inclusion of GRB150101B, GRB050724A, GRB061201, GRB080905A, GRB150424A, and GRB160821B) and the upper limits from all the other sGRBs not associated with any kilonova detection we obtain for the first time a kilonova luminosity distribution in different bands.
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18.
  • Crockett, Katie, et al. (författare)
  • Experiences of Health Care Access Challenges for Back Pain Care Across the Rural-Urban Continuum in Canada: Protocol for Cross-sectional Research
  • 2022
  • Ingår i: JMIR Research Protocols. - : JMIR Publications Inc.. - 1929-0748. ; 11:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Back pain is common and costly, with negative impacts on both individuals and the health care system. Rural, remote, and Indigenous populations are at greater risk of experiencing back pain compared to urban and non-Indigenous populations. Potential barriers to health care access among Canadians with chronic back pain (CBP) have been identified; however, no study has used lived experiences of people with CBP to drive the selection, analysis, and interpretation of variables most meaningful to patients. Objective: The aims of this study are to (1) engage with rural, remote, and urban Indigenous and non-Indigenous patients, health care providers, and health system decision makers to explore lived experiences among people with CBP in Saskatchewan, Canada; (2) cocreate meaningful indicators of CBP care access and effectiveness; and (3) identify program and policy recommendations to overcome access barriers to CBP care. Methods: In phase 1, one-on-one interviews with 30 people with current or past CBP and 10 health care providers residing or practicing in rural, remote, or urban Saskatchewan communities will be conducted. We will recruit Indigenous (n=10) and non-Indigenous (n=20) rural, remote, and urban people. In phase 2, findings from the interviews will inform development of a population-based telephone survey focused on access to health care barriers and facilitators among rural, remote, and urban people; this survey will be administered to 383 residents with CBP across Saskatchewan. In phase 3, phase 1 and 2 findings will be presented to provincial and national policy makers; health system decision makers; health care providers; rural, remote, and urban people with CBP and their communities; and other knowledge users at an interactive end-of-project knowledge translation event. A World Café method will facilitate interactive dialogue designed to catalyze future patient-oriented research and pathways to improve access to CBP care. Patient engagement will be conducted, wherein people with lived experience of CBP, including Indigenous and non-Indigenous people from rural, remote, and urban communities (ie, patient partners), are equal members of the research team. Patient partners are engaged throughout the research process, providing unique knowledge to ensure more comprehensive collection of data while shaping culturally appropriate messages and methods of sharing findings to knowledge users. Results: Participant recruitment began in January 2021. Phase 1 interviews occurred between January 2021 and September 2022. Phase 2 phone survey was administered in May 2022. Final results are anticipated in late 2022. Conclusions: This study will privilege patient experiences to better understand current health care use and potential access challenges and facilitators among rural, remote, and urban people with CBP in Saskatchewan. We aim to inform the development of comprehensive measures that will be sensitive to geographical location and relevant to culturally diverse people with CBP, ultimately leading to enhanced access to more patient-centered care for CBP. International Registered Report Identifier (IRRID): DERR1-10.2196/42484
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19.
  • Crockett, Katie, et al. (författare)
  • Healthcare Access Challenges and Facilitators for Back Pain Across the Rural-Urban Continuum in Saskatchewan, Canada : Cross-Sectional Results From a Provincial-Wide Telephone Survey
  • 2023
  • Ingår i: Health Services Insights. - : SAGE Publications. - 1178-6329. ; 16
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Chronic back pain is a common musculoskeletal disorder, disproportionately affecting rural and Indigenous people. Saskatchewan has a relatively high proportion of rural and Indigenous residents; therefore, understanding barriers and facilitators to accessing healthcare are needed to improve healthcare service delivery. Methods: A provincial-wide telephone survey explored experiences and perceived healthcare access barriers and facilitators among 384 Saskatchewan residents who experienced chronic low back pain. Chi-squared tests were performed to determine if people who lived in urban versus rural areas differed in the proportion who had accessed services from various healthcare practitioners. T-test and Mann-Whitney U analyses were conducted to determine differences between urban and rural, and Indigenous and non-Indigenous respondents. Results: Of 384 residents surveyed, 234 (60.9%) reported living in a rural location; 21 (5.5%) identified as Indigenous. Wait times (47%), cost (40%), travel (39%), and not knowing how to seek help (37%) were the most common barriers for Saskatchewan residents seeking care, with travel being the only barrier that was significantly different between rural and urban respondents (P ⩽.001). Not knowing where to go to access care or what would help their low back pain (P =.03), lack of cultural sensitivity (P =.007), and comfort discussing problems with health care professionals (P =.26) were greater barriers for Indigenous than non-Indigenous participants. Top facilitators (>50% of respondents) included publicly funded healthcare, locally accessible healthcare services, and having supportive healthcare providers who facilitate referral to appropriate care, with urban respondents considering the latter 2 as greater facilitators than rural respondents. Telehealth or virtual care (P =.013) and having healthcare options nearby in their community (P =.045) were greater facilitators among Indigenous participants compared to non-Indigenous respondents. Conclusions: Rural, urban, Indigenous, and non-Indigenous people report overlapping and unique barriers and facilitators to accessing care for chronic low back pain. Understanding perceived access experiences will assist in developing more effective care models for specific communities or regions.
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20.
  • Crockett, Katie, et al. (författare)
  • “Navigating chaos”: Urban, Rural, and Remote Patient Experiences in Accessing Healthcare with Indigenous and Non-Indigenous Perspectives of Living with Chronic Low Back Pain
  • 2024
  • Ingår i: Canadian Journal of Pain. - : Informa UK Limited. - 2474-0527. ; 8:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Healthcare access for chronic low back pain is complex and should consider not only the health system, but patient care seeking experiences as well. People who live in rural and remote communities and/or identify as being Indigenous may often encounter additional barriers to accessing care for chronic low back pain; thus, these contexts must be considered to fully understand barriers and facilitators. Aims: The aim of this study was to understand care-seeking experiences of people living with chronic back pain in Saskatchewan and determine unique experiences facing urban, rural, remote, and/or Indigenous peoples. Methods: Thirty-three participants with chronic low back pain completed a preliminary survey followed by individual semistructured interviews. Participants were categorized as urban, rural, or remote including Indigenous status. A qualitative interpretive research approach with inductive thematic analysis was employed. Results: Three overarching themes were identified with the following subthemes: (1) healthcare access challenges: challenges to accessing care, challenges within the health system, and challenges leading to self-directed management/coping strategies; (2) healthcare access facilitators: funded care, participant education and knowledge, patient–provider communication, and care closer to home; and (3) participant recommendations for improved care provision: coordination of care, integrative and holistic care, and patient-centered care and support. Rural and remote participants highlighted travel as a main barrier. Indigenous participant experiences emphasized communication with healthcare providers and past experiences influencing desire to access care. Conclusion: Participants identified a range of challenges and facilitators as well as recommendations for improving access to care for chronic low back pain, with unique barriers for rural, remote, and Indigenous participants.
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21.
  • McDonald, Robert I., et al. (författare)
  • Research gaps in knowledge of the impact of urban growth on biodiversity
  • 2020
  • Ingår i: Nature Sustainability. - : Springer Science and Business Media LLC. - 2398-9629. ; 3:1, s. 16-24
  • Forskningsöversikt (refereegranskat)abstract
    • By 2030, an additional 1.2 billion people are forecast in urban areas globally. We review the scientific literature (n = 922 studies) to assess direct and indirect impacts of urban growth on habitat and biodiversity. Direct impacts are cumulatively substantial, with 290,000 km(2) of natural habitat forecast to be converted to urban land uses between 2000 and 2030. Studies of direct impact are disproportionately from high-income countries. Indirect urban impacts on biodiversity, such as food consumption, affect a greater area than direct impacts, but comparatively few studies (34%) have quantified urban indirect impacts on biodiversity. The world is urbanizing. This Review assesses impacts of urban growth on habitat and biodiversity, finding direct impacts more in high-income countries while indirect impacts affect more land but are lesser studied.
  •  
22.
  • Schneider, E, et al. (författare)
  • CD73-mediated adenosine production by CD8 T cell-derived extracellular vesicles constitutes an intrinsic mechanism of immune suppression
  • 2021
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 5911-
  • Tidskriftsartikel (refereegranskat)abstract
    • Immune cells at sites of inflammation are continuously activated by local antigens and cytokines, and regulatory mechanisms must be enacted to control inflammation. The stepwise hydrolysis of extracellular ATP by ectonucleotidases CD39 and CD73 generates adenosine, a potent immune suppressor. Here we report that human effector CD8 T cells contribute to adenosine production by releasing CD73-containing extracellular vesicles upon activation. These extracellular vesicles have AMPase activity, and the resulting adenosine mediates immune suppression independently of regulatory T cells. In addition, we show that extracellular vesicles isolated from the synovial fluid of patients with juvenile idiopathic arthritis contribute to T cell suppression in a CD73-dependent manner. Our results suggest that the generation of adenosine upon T cell activation is an intrinsic mechanism of human effector T cells that complements regulatory T cell-mediated suppression in the inflamed tissue. Finally, our data underscore the role of immune cell-derived extracellular vesicles in the control of immune responses.
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23.
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