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1.
  • Thomas, HS, et al. (författare)
  • 2019
  • swepub:Mat__t
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  • Reiner, A. T., et al. (författare)
  • Concise Review: Developing Best-Practice Models for the Therapeutic Use of Extracellular Vesicles
  • 2017
  • Ingår i: Stem Cells Translational Medicine. - : Oxford University Press (OUP). - 2157-6564 .- 2157-6580. ; 6:8
  • Forskningsöversikt (refereegranskat)abstract
    • Growing interest in extracellular vesicles (EVs, including exosomes and microvesicles) as therapeutic entities, particularly in stem cell-related approaches, has underlined the need for standardization and coordination of development efforts. Members of the International Society for Extracellular Vesicles and the Society for Clinical Research and Translation of Extracellular Vesicles Singapore convened a Workshop on this topic to discuss the opportunities and challenges associated with development of EV-based therapeutics at the preclinical and clinical levels. This review outlines topic-specific action items that, if addressed, will enhance the development of best-practice models for EV therapies.
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  • Ademuyiwa, Adesoji O., et al. (författare)
  • Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
  • 2016
  • Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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  • Cunningham, A. L., et al. (författare)
  • Efficacy of the Herpes Zoster Subunit Vaccine in Adults 70 Years of Age or Older
  • 2016
  • Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 375:11, s. 1019-1032
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND A trial involving adults 50 years of age or older (ZOE-50) showed that the herpes zoster subunit vaccine (HZ/su) containing recombinant varicella-zoster virus glycoprotein E and the AS01(B) adjuvant system was associated with a risk of herpes zoster that was 97.2% lower than that associated with placebo. A second trial was performed concurrently at the same sites and examined the safety and efficacy of HZ/su in adults 70 years of age or older (ZOE-70). METHODS This randomized, placebo-controlled, phase 3 trial was conducted in 18 countries and involved adults 70 years of age or older. Participants received two doses of HZ/su or placebo (assigned in a 1: 1 ratio) administered intramuscularly 2 months apart. Vaccine efficacy against herpes zoster and postherpetic neuralgia was assessed in participants from ZOE-70 and in participants pooled from ZOE-70 and ZOE-50. RESULTS In ZOE-70, 13,900 participants who could be evaluated (mean age, 75.6 years) received either HZ/su (6950 participants) or placebo (6950 participants). During a mean follow-up period of 3.7 years, herpes zoster occurred in 23 HZ/su recipients and in 223 placebo recipients (0.9 vs. 9.2 per 1000 person-years). Vaccine efficacy against herpes zoster was 89.8% (95% confidence interval [CI], 84.2 to 93.7; P<0.001) and was similar in participants 70 to 79 years of age (90.0%) and participants 80 years of age or older (89.1%). In pooled analyses of data from participants 70 years of age or older in ZOE-50 and ZOE-70 (16,596 participants), vaccine efficacy against herpes zoster was 91.3% (95% CI, 86.8 to 94.5; P<0.001), and vaccine efficacy against postherpetic neuralgia was 88.8% (95% CI, 68.7 to 97.1; P<0.001). Solicited reports of injection-site and systemic reactions within 7 days after injection were more frequent among HZ/su recipients than among placebo recipients (79.0% vs. 29.5%). Serious adverse events, potential immune-mediated diseases, and deaths occurred with similar frequencies in the two study groups. CONCLUSIONS In our trial, HZ/su was found to reduce the risks of herpes zoster and postherpetic neuralgia among adults 70 years of age or older. (Funded by GlaxoSmithKline Biologicals; ZOE-50 and ZOE-70 ClinicalTrials.govnumbers, NCT01165177 and NCT01165229.)
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  • Kalman, L. V., et al. (författare)
  • Pharmacogenetic allele nomenclature: International workgroup recommendations for test result reporting
  • 2016
  • Ingår i: Clinical Pharmacology and Therapeutics. - : WILEY-BLACKWELL. - 0009-9236 .- 1532-6535. ; 99:2, s. 172-185
  • Tidskriftsartikel (refereegranskat)abstract
    • This article provides nomenclature recommendations developed by an international workgroup to increase transparency and standardization of pharmacogenetic (PGx) result reporting. Presently, sequence variants identified by PGx tests are described using different nomenclature systems. In addition, PGx analysis may detect different sets of variants for each gene, which can affect interpretation of results. This practice has caused confusion and may thereby impede the adoption of clinical PGx testing. Standardization is critical to move PGx forward.
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9.
  • Lønborg, C., et al. (författare)
  • A global database of dissolved organic matter (DOM) concentration measurements in coastal waters (CoastDOM v1)
  • 2024
  • Ingår i: Earth System Science Data. - : Copernicus Publications. - 1866-3508 .- 1866-3516. ; 16:2, s. 1107-1119
  • Tidskriftsartikel (refereegranskat)abstract
    • Measurements of dissolved organic carbon (DOC), nitrogen (DON), and phosphorus (DOP) concentrations are used to characterize the dissolved organic matter (DOM) pool and are important components ofbiogeochemical cycling in the coastal ocean. Here, we present the first edition of a global database (CoastDOMv1; available at https://doi.org/10.1594/PANGAEA.964012, Lønborg et al., 2023) compiling previously published and unpublished measurements of DOC, DON, and DOP in coastal waters. These data are complementedby hydrographic data such as temperature and salinity and, to the extent possible, other biogeochemical variables(e.g. chlorophyll a, inorganic nutrients) and the inorganic carbon system (e.g. dissolved inorganic carbon andtotal alkalinity). Overall, CoastDOM v1 includes observations of concentrations from all continents. However,most data were collected in the Northern Hemisphere, with a clear gap in DOM measurements from the SouthernHemisphere. The data included were collected from 1978 to 2022 and consist of 62 338 data points for DOC,20 356 for DON, and 13 533 for DOP. The number of measurements decreases progressively in the sequenceDOC > DON > DOP, reflecting both differences in the maturity of the analytical methods and the greater focuson carbon cycling by the aquatic science community. The global database shows that the average DOC concentration in coastal waters (average ± standard deviation (SD): 182±314 µmolC L−1; median: 103 µmolC L−1) is13-fold higher than the average coastal DON concentration (13.6 ± 30.4 µmol N L−1; median: 8.0 µmol N L−1),which is itself 39-fold higher than the average coastal DOP concentration (0.34 ± 1.11 µmol P L−1; median:0.18 µmol P L−1). This dataset will be useful for identifying global spatial and temporal patterns in DOM and willhelp facilitate the reuse of DOC, DON, and DOP data in studies aimed at better characterizing local biogeochemical processes; closing nutrient budgets; estimating carbon, nitrogen, and phosphorous pools; and establishing abaseline for modelling future changes in coastal waters. 
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  • Xie, F., et al. (författare)
  • Cross-cultural adaptation and validation of Singapore English and Chinese versions of the Knee injury and Osteoarthritis Outcome Score (KOOS) in Asians with knee osteoarthritis in Singapore
  • 2006
  • Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 14:11, s. 1098-1103
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To cross-culturally adapt and validate Singapore English and Chinese versions of the Knee injury and Osteoarthritis Outcome Score (KOOS) in patients with knee osteoarthritis (OA) in Singapore. Methods: Singapore English and Chinese versions were cross-culturally adapted from the source English KOOS following standard guidelines (including cognitive debriefing). Patients were asked to complete identical questionnaires containing the KOOS, Short Form 36 Health Survey, and EQ-5D twice within 6 days. Reliability was assessed using Cronbach's alpha and intraclass correlation coefficients (ICC), dimensionality using item-to-domain correlations and convergent and divergent construct validity using 14 and 13 a priori hypotheses, respectively. Results: Singapore English and Chinese KOOS versions were well accepted by patients in pilot testing and were therefore administered to a consecutive sample of 127 English and 131 Chinese-speaking Singaporeans with knee OA. Cronbach's alpha exceeded 0.7 for all domains except for Chinese pain and symptoms domains. ICC exceeded 0.7 for all domains except for English sport and recreation and Chinese knee-related QoL domains. Hypothesized item-to-domain correlations (Spearman's rho >= 0.4) were observed for 38 items in English and 29 in Chinese versions. Convergent construct validity was supported by the presence of hypothesized moderate/strong correlations (rho = 0.37-0.65) for 13 and 11 a priori hypotheses in the English and Chinese KOOS, respectively. Divergent construct validity was supported by the presence of weak correlations (rho = 0.02-0.34) for 12 and 11 a priori hypotheses in the English and Chinese KOOS, respectively. Conclusion: The Singapore English and Chinese KOOS were well accepted and demonstrated acceptable reliability and validity in Asian patients with knee OA in Singapore. (C) 2006 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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  • Bethlehem, RAI, et al. (författare)
  • Brain charts for the human lifespan
  • 2022
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 604:79057906, s. 525-
  • Tidskriftsartikel (refereegranskat)abstract
    • Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight1. Here we assemble an interactive open resource to benchmark brain morphology derived from any current or future sample of MRI data (http://www.brainchart.io/). With the goal of basing these reference charts on the largest and most inclusive dataset available, acknowledging limitations due to known biases of MRI studies relative to the diversity of the global population, we aggregated 123,984 MRI scans, across more than 100 primary studies, from 101,457 human participants between 115 days post-conception to 100 years of age. MRI metrics were quantified by centile scores, relative to non-linear trajectories2 of brain structural changes, and rates of change, over the lifespan. Brain charts identified previously unreported neurodevelopmental milestones3, showed high stability of individuals across longitudinal assessments, and demonstrated robustness to technical and methodological differences between primary studies. Centile scores showed increased heritability compared with non-centiled MRI phenotypes, and provided a standardized measure of atypical brain structure that revealed patterns of neuroanatomical variation across neurological and psychiatric disorders. In summary, brain charts are an essential step towards robust quantification of individual variation benchmarked to normative trajectories in multiple, commonly used neuroimaging phenotypes.
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  • Calvert, Clara, et al. (författare)
  • Changes in preterm birth and stillbirth during COVID-19 lockdowns in 26 countries
  • 2023
  • Ingår i: Nature Human Behaviour. - : Springer Nature. - 2397-3374. ; 7:4, s. 529-544
  • Tidskriftsartikel (refereegranskat)abstract
    • Preterm birth (PTB) is the leading cause of infant mortality worldwide. Changes in PTB rates, ranging from -90% to +30%, were reported in many countries following early COVID-19 pandemic response measures ('lockdowns'). It is unclear whether this variation reflects real differences in lockdown impacts, or perhaps differences in stillbirth rates and/or study designs. Here we present interrupted time series and meta-analyses using harmonized data from 52 million births in 26 countries, 18 of which had representative population-based data, with overall PTB rates ranging from 6% to 12% and stillbirth ranging from 2.5 to 10.5 per 1,000 births. We show small reductions in PTB in the first (odds ratio 0.96, 95% confidence interval 0.95-0.98, P value <0.0001), second (0.96, 0.92-0.99, 0.03) and third (0.97, 0.94-1.00, 0.09) months of lockdown, but not in the fourth month of lockdown (0.99, 0.96-1.01, 0.34), although there were some between-country differences after the first month. For high-income countries in this study, we did not observe an association between lockdown and stillbirths in the second (1.00, 0.88-1.14, 0.98), third (0.99, 0.88-1.12, 0.89) and fourth (1.01, 0.87-1.18, 0.86) months of lockdown, although we have imprecise estimates due to stillbirths being a relatively rare event. We did, however, find evidence of increased risk of stillbirth in the first month of lockdown in high-income countries (1.14, 1.02-1.29, 0.02) and, in Brazil, we found evidence for an association between lockdown and stillbirth in the second (1.09, 1.03-1.15, 0.002), third (1.10, 1.03-1.17, 0.003) and fourth (1.12, 1.05-1.19, <0.001) months of lockdown. With an estimated 14.8 million PTB annually worldwide, the modest reductions observed during early pandemic lockdowns translate into large numbers of PTB averted globally and warrant further research into causal pathways.
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  • Challis, B G, et al. (författare)
  • Mice lacking pro-opiomelanocortin are sensitive to high-fat feeding but respond normally to the acute anorectic effects of peptide-YY(3-36).
  • 2004
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 101:13, s. 4695-700
  • Tidskriftsartikel (refereegranskat)abstract
    • Inactivating mutations of the pro-opiomelanocortin (POMC) gene in both mice and humans leads to hyperphagia and obesity. To further examine the mechanisms whereby POMC-deficiency leads to disordered energy homeostasis, we have generated mice lacking all POMC-derived peptides. Consistent with a previously reported model, Pomc(-/-) mice were obese and hyperphagic. They also showed reduced resting oxygen consumption associated with lowered serum levels of thyroxine. Hypothalami from Pomc(-/-) mice showed markedly increased expression of melanin-concentrating hormone mRNA in the lateral hypothalamus, but expression of neuropeptide Y mRNA in the arcuate nucleus was not altered. Provision of a 45% fat diet increased energy intake and body weight in both Pomc(-/-) and Pomc(+/-) mice. The effects of leptin on food intake and body weight were blunted in obese Pomc(-/-) mice whereas nonobese Pomc(-/-) mice were sensitive to leptin. Surprisingly, we found that Pomc(-/-) mice maintained their acute anorectic response to peptide-YY(3-36) (PYY(3-36)). However, 7 days of PYY(3-36) administration had no effect on cumulative food intake or body weight in wild-type or Pomc(-/-) mice. Thus, POMC peptides seem to be necessary for the normal response of energy balance to high-fat feeding, but not for the acute anorectic effect of PYY(3-36) or full effects of leptin on feeding. The finding that the loss of only one copy of the Pomc gene is sufficient to render mice susceptible to the effects of high fat feeding emphasizes the potential importance of this locus as a site for gene-environment interactions predisposing to obesity.
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  • Chaurasia, Chandra S., et al. (författare)
  • AAPS-FDA workshop white paper : microdialysis principles, application and regulatory perspectives
  • 2007
  • Ingår i: Pharmaceutical research. - : Springer Science and Business Media LLC. - 0724-8741 .- 1573-904X. ; 24:5, s. 1014-1025
  • Tidskriftsartikel (refereegranskat)abstract
    • Many decisions in drug development and medical practice are based on measuring blood concentrations of endogenous and exogenous molecules. Yet most biochemical and pharmacological events take place in the tissues. Also, most drugs with few notable exceptions exert their effects not within the bloodstream, but in defined target tissues into which drugs have to distribute from the central compartment. Assessing tissue drug chemistry has, thus, for long been viewed as a more rational way to provide clinically meaningful data rather than gaining information from blood samples. More specifically, it is often the extracellular (interstitial) tissue space that is most closely related to the site of action (biophase) of the drug. Currently microdialysis (microD) is the only tool available that explicitly provides data on the extracellular space. Although microD as a preclinical and clinical tool has been available for two decades, there is still uncertainty about the use of microD in drug research and development, both from a methodological and a regulatory point of view. In an attempt to reduce this uncertainty and to provide an overview of the principles and applications of microD in preclinical and clinical settings, an AAPS-FDA workshop took place in November 2005 in Nashville, TN, USA. Stakeholders from academia, industry and regulatory agencies presented their views on microD as a tool in drug research and development.
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  • Chaurasia, Chandra S., et al. (författare)
  • AAPS-FDA Workshop White Paper : microdialysis principles, application, and regulatory perspectives
  • 2007
  • Ingår i: Journal of clinical pharmacology. - : Wiley. - 0091-2700 .- 1552-4604. ; 47:5, s. 589-603
  • Tidskriftsartikel (refereegranskat)abstract
    • Many decisions in drug development and medical practice are based on measuring blood concentrations of endogenous and exogenous molecules. Yet most biochemical and pharmacological events take place in the tissues. Also, most drugs with few notable exceptions exert their effects not within the bloodstream, but in defined target tissues into which drugs have to distribute from the central compartment. Assessing tissue drug chemistry has, thus, for long been viewed as a more rational way to provide clinically meaningful data rather than gaining information from blood samples. More specifically, it is often the extracellular (interstitial) tissue space that is most closely related to the site of action (biophase) of the drug. Currently microdialysis (μD) is the only tool available that explicitly provides data on the extracellular space. Although μD as a preclinical and clinical tool has been available for two decades, there is still uncertainty about the use of μD in drug research and development, both from a methodological and a regulatory point of view. In an attempt to reduce this uncertainty and to provide an overview of the principles and applications of μD in preclinical and clinical settings, an AAPS-FDA workshop took place in November 2005 in Nashville, TN, USA. Stakeholders from academia, industry and regulatory agencies presented their views on μD as a tool in drug research and development.
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20.
  • Clement, R. Carter, et al. (författare)
  • A proposed set of metrics for standardized outcome reporting in the management of low back pain
  • 2015
  • Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3682 .- 1745-3674. ; 86:5, s. 523-533
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and purpose - Outcome measurement has been shown to improve performance in several fields of healthcare. This understanding has driven a growing interest in value-based healthcare, where value is defined as outcomes achieved per money spent. While low back pain (LBP) constitutes an enormous burden of disease, no universal set of metrics has yet been accepted to measure and compare outcomes. Here, we aim to define such a set. Patients and methods - An international group of 22 specialists in several disciplines of spine care was assembled to review literature and select LBP outcome metrics through a 6-round modified Delphi process. The scope of the outcome set was degenerative lumbar conditions. Results - Patient-reported metrics include numerical pain scales, lumbar-related function using the Oswestry disability index, health-related quality of life using the EQ-5D-3L questionnaire, and questions assessing work status and analgesic use. Specific common and serious complications are included. Recommended follow-up intervals include 6, 12, and 24 months after initiating treatment, with optional follow-up at 3 months and 5 years. Metrics for risk stratification are selected based on preexisting tools. Interpretation - The outcome measures recommended here are structured around specific etiologies of LBP, span a patient's entire cycle of care, and allow for risk adjustment. Thus, when implemented, this set can be expected to facilitate meaningful comparisons and ultimately provide a continuous feedback loop, enabling ongoing improvements in quality of care. Much work lies ahead in implementation, revision, and validation of this set, but it is an essential first step toward establishing a community of LBP providers focused on maximizing the value of the care we deliver.
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  • Groot, Colin, et al. (författare)
  • Latent atrophy factors related to phenotypical variants of posterior cortical atrophy
  • 2020
  • Ingår i: Neurology. - 1526-632X. ; 95:12, s. 1672-1685
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To determine whether atrophy relates to phenotypical variants of posterior cortical atrophy (PCA) recently proposed in clinical criteria (i.e., dorsal, ventral, dominant-parietal, and caudal) we assessed associations between latent atrophy factors and cognition. METHODS: We employed a data-driven Bayesian modeling framework based on latent Dirichlet allocation to identify latent atrophy factors in a multicenter cohort of 119 individuals with PCA (age 64 ± 7 years, 38% male, Mini-Mental State Examination 21 ± 5, 71% β-amyloid positive, 29% β-amyloid status unknown). The model uses standardized gray matter density images as input (adjusted for age, sex, intracranial volume, MRI scanner field strength, and whole-brain gray matter volume) and provides voxelwise probabilistic maps for a predetermined number of atrophy factors, allowing every individual to express each factor to a degree without a priori classification. Individual factor expressions were correlated to 4 PCA-specific cognitive domains (object perception, space perception, nonvisual/parietal functions, and primary visual processing) using general linear models. RESULTS: The model revealed 4 distinct yet partially overlapping atrophy factors: right-dorsal, right-ventral, left-ventral, and limbic. We found that object perception and primary visual processing were associated with atrophy that predominantly reflects the right-ventral factor. Furthermore, space perception was associated with atrophy that predominantly represents the right-dorsal and right-ventral factors. However, individual participant profiles revealed that the large majority expressed multiple atrophy factors and had mixed clinical profiles with impairments across multiple domains, rather than displaying a discrete clinical-radiologic phenotype. CONCLUSION: Our results indicate that specific brain behavior networks are vulnerable in PCA, but most individuals display a constellation of affected brain regions and symptoms, indicating that classification into 4 mutually exclusive variants is unlikely to be clinically useful.
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  • KC, Ashish, 1982-, et al. (författare)
  • Changes in preterm birth and stillbirth during COVID-19 lockdowns in 26 countries.
  • 2023
  • Ingår i: Nature human behaviour. - : Springer Science and Business Media LLC. - 2397-3374. ; 7:4, s. 529-544
  • Tidskriftsartikel (refereegranskat)abstract
    • Preterm birth (PTB) is the leading cause of infant mortality worldwide. Changes in PTB rates, ranging from -90% to +30%, were reported in many countries following early COVID-19 pandemic response measures ('lockdowns'). It is unclear whether this variation reflects real differences in lockdown impacts, or perhaps differences in stillbirth rates and/or study designs. Here we present interrupted time series and meta-analyses using harmonized data from 52 million births in 26 countries, 18 of which had representative population-based data, with overall PTB rates ranging from 6% to 12% and stillbirth ranging from 2.5 to 10.5 per 1,000 births. We show small reductions in PTB in the first (odds ratio 0.96, 95% confidence interval 0.95-0.98, P value <0.0001), second (0.96, 0.92-0.99, 0.03) and third (0.97, 0.94-1.00, 0.09) months of lockdown, but not in the fourth month of lockdown (0.99, 0.96-1.01, 0.34), although there were some between-country differences after the first month. For high-income countries in this study, we did not observe an association between lockdown and stillbirths in the second (1.00, 0.88-1.14, 0.98), third (0.99, 0.88-1.12, 0.89) and fourth (1.01, 0.87-1.18, 0.86) months of lockdown, although we have imprecise estimates due to stillbirths being a relatively rare event. We did, however, find evidence of increased risk of stillbirth in the first month of lockdown in high-income countries (1.14, 1.02-1.29, 0.02) and, in Brazil, we found evidence for an association between lockdown and stillbirth in the second (1.09, 1.03-1.15, 0.002), third (1.10, 1.03-1.17, 0.003) and fourth (1.12, 1.05-1.19, <0.001) months of lockdown. With an estimated 14.8 million PTB annually worldwide, the modest reductions observed during early pandemic lockdowns translate into large numbers of PTB averted globally and warrant further research into causal pathways.
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28.
  • López-Fauqued, M., et al. (författare)
  • Safety profile of the adjuvanted recombinant zoster vaccine : Pooled analysis of two large randomised phase 3 trials
  • 2019
  • Ingår i: Vaccine. - : Elsevier Ltd. - 0264-410X .- 1873-2518. ; 37:18, s. 2482-2493
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229) phase 3 clinical trials showed that the adjuvanted recombinant zoster vaccine (RZV) was ≥90% efficacious in preventing herpes zoster in adults. Here we present a comprehensive overview of the safety data from these studies. Methods: Adults aged ≥50 (ZOE-50) and ≥70 (ZOE-70) years were randomly vaccinated with RZV or placebo. Safety analyses were performed on the pooled total vaccinated cohort, consisting of participants receiving at least one dose of RZV or placebo. Solicited and unsolicited adverse events (AEs) were collected for 7 and 30 days after each vaccination, respectively. Serious AEs (SAEs) were collected from the first vaccination until 12 months post-last dose. Fatal AEs, vaccination-related SAEs, and potential immune-mediated diseases (pIMDs) were collected during the entire study period. Results: Safety was evaluated in 14,645 RZV and 14,660 placebo recipients. More RZV than placebo recipients reported unsolicited AEs (50.5% versus 32.0%); the difference was driven by transient injection site and solicited systemic reactions that were generally seen in the first week post-vaccination. The occurrence of overall SAEs (RZV: 10.1%; Placebo: 10.4%), fatal AEs (RZV: 4.3%; Placebo: 4.6%), and pIMDs (RZV: 1.2%; Placebo: 1.4%) was balanced between groups. The occurrence of possible exacerbations of pIMDs was rare and similar between groups. Overall, except for the expected local and systemic symptoms, the safety results were comparable between the RZV and Placebo groups irrespective of participant age, gender, or race. Conclusions: No safety concerns arose, supporting the favorable benefit-risk profile of RZV. © 2019 GlaxoSmithKline Biologicals SA
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  • Meyer, L, et al. (författare)
  • Thrombectomy for secondary distal, medium vessel occlusions of the posterior circulation: seeking complete reperfusion
  • 2022
  • Ingår i: Journal of neurointerventional surgery. - : BMJ. - 1759-8486 .- 1759-8478. ; 14:7, s. 654-659
  • Tidskriftsartikel (refereegranskat)abstract
    • Whether to approach distal occlusions endovascularly or not in medium-sized vessels secondary to proximal large vessel occlusion stroke remains unanswered.ObjectiveTo investigates the technical feasibility and safety of thrombectomy for secondary posterior circulation distal, medium vessel occlusions (DMVO).MethodsTOPMOST (Treatment fOr Primary Medium vessel Occlusion STroke) is an international, retrospective, multicenter, observational registry of patients treated for distal cerebral artery occlusions. This study subanalysis endovascularly treated occlusions of the posterior cerebral artery in the P2 and P3 segment secondary preprocedural or periprocedural thrombus migration between January 2014 and June 2020. Technical feasibility was evaluated with the modified Thrombolysis in Cerebral Infarction (mTICI) scale. Procedural safety was assessed by the occurrence of symptomatic intracranial hemorrhage (sICH) and intervention-related serious adverse events.ResultsAmong 71 patients with secondary posterior circulation DMVO who met the inclusion criteria, occlusions were present in 80.3% (57/71) located in the P2 segment and in 19.7% (14/71) in the P3 segment. Periprocedural migration occurred in 54.9% (39/71) and preprocedural migration in 45.1% (32/71) of cases. The first reperfusion attempt led in 38% (27/71) of all cases to mTICI 3. On multivariable logistic regression analysis, increased numbers of reperfusion attempts (adjusted odds ratio (aOR)=0.39, 95% CI 0.29 to 0.88, p=0.009) and preprocedural migration (aOR=4.70, 95% CI,1.35 to 16.35, p=0.015) were significantly associated with mTICI 3. sICH occurred in 2.8% (2/71).ConclusionThrombectomy for secondary posterior circulation DMVO seems to be safe and technically feasible. Even though thrombi that have migrated preprocedurally may be easier to retract, successful reperfusion can be achieved in the majority of patients with secondary DMVO of the P2 and P3 segment.
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36.
  • Pfeffer, M. A., et al. (författare)
  • Ground-Based measurements of the 2014-2015 holuhraun volcanic cloud (Iceland)
  • 2018
  • Ingår i: Geosciences (Switzerland). - : MDPI AG. - 2076-3263. ; 8:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The 2014-2015 Bárðarbunga fissure eruption at Holuhraun in central Iceland was distinguished by the high emission of gases, in total 9.6 Mt SO 2 , with almost no tephra. This work collates all ground-based measurements of this extraordinary eruption cloud made under particularly challenging conditions: remote location, optically dense cloud with high SO 2 column amounts, low UV intensity, frequent clouds and precipitation, an extensive and hot lava field, developing ramparts, and high-latitude winter conditions. Semi-continuous measurements of SO 2 flux with three scanning DOAS instruments were augmented by car traverses along the ring-road and along the lava. The ratios of other gases/SO 2 were measured by OP-FTIR, MultiGAS, and filter packs. Ratios of SO 2 /HCl = 30-110 and SO 2 /HF = 30-130 show a halogen-poor eruption cloud. Scientists on-site reported extremely minor tephra production during the eruption. OPC and filter packs showed low particle concentrations similar to non-eruption cloud conditions. Three weather radars detected a droplet-rich eruption cloud. Top of eruption cloud heights of 0.3-5.5 km agl were measured with ground-and aircraft-based visual observations, web camera and NicAIR II infrared images, triangulation of scanning DOAS instruments, and the location of SO 2 peaks measured by DOAS traverses. Cloud height and emission rate measurements were critical for initializing gas dispersal simulations for hazard forecasting.
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37.
  • Qin, Yue, et al. (författare)
  • A multi-scale map of cell structure fusing protein images and interactions
  • 2021
  • Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 600:7889, s. 536-
  • Tidskriftsartikel (refereegranskat)abstract
    • The cell is a multi-scale structure with modular organization across at least four orders of magnitude(1). Two central approaches for mapping this structure-protein fluorescent imaging and protein biophysical association-each generate extensive datasets, but of distinct qualities and resolutions that are typically treated separately(2,3). Here we integrate immunofluorescence images in the Human Protein Atlas(4) with affinity purifications in BioPlex(5) to create a unified hierarchical map of human cell architecture. Integration is achieved by configuring each approach as a general measure of protein distance, then calibrating the two measures using machine learning. The map, known as the multi-scale integrated cell (MuSIC 1.0), resolves 69 subcellular systems, of which approximately half are to our knowledge undocumented. Accordingly, we perform 134 additional affinity purifications and validate subunit associations for the majority of systems. The map reveals a pre-ribosomal RNA processing assembly and accessory factors, which we show govern rRNA maturation, and functional roles for SRRM1 and FAM120C in chromatin and RPS3A in splicing. By integration across scales, MuSIC increases the resolution of imaging while giving protein interactions a spatial dimension, paving the way to incorporate diverse types of data in proteome-wide cell maps.
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39.
  • Smith, Stuart W., et al. (författare)
  • Tree species that 'live slow, die older' enhance tropical peat swamp restoration : Evidence from a systematic review
  • 2022
  • Ingår i: Journal of Applied Ecology. - : Wiley. - 0021-8901 .- 1365-2664. ; 59:8, s. 1950-1966
  • Forskningsöversikt (refereegranskat)abstract
    • 1. Degraded tropical peatlands lack tree cover and are often subject to seasonal flooding and repeated burning. These harsh environments for tree seedlings to survive and grow are therefore challenging to revegetate. Knowledge on species performance from previous plantings represents an important evidence base to help guide future tropical peat swamp forest (TPSF) restoration efforts.2. We conducted a systematic review of the survival and growth of tree species planted in degraded peatlands across Southeast Asia to examine (1) species differences, (2) the impact of seedling and site treatments on survival and growth and (3) the potential use of plant functional traits to predict seedling survival and growth rates.3. Planted seedling monitoring data were compiled through a systematic review of journal articles, conference proceedings, reports, theses and unpublished datasets. In total, 94 study-sites were included, spanning three decades from 1988 to 2019, and including 141 indigenous peatland tree and palm species. Accounting for variable planting numbers and monitoring durations, we analysed three measures of survival and growth: (1) final survival weighted by the number of seedlings planted, (2) half-life, that is, duration until 50% mortality and (3) relative growth rates (RGR) corrected for initial planting height of seedlings.4. Average final survival was 62% and half-life was 33 months across all species, sites and treatments. Species differed significantly in survival and half-life. Seedling and site treatments had small effects with the strongest being higher survival of mycorrhizal fungi inoculated seedlings; lower survival, half-life and RGR when shading seedlings; and lower RGR and higher survival when fertilising seedlings. Leaf nutrient and wood density traits predicted TPSF species survival, but not half-life and RGR. RGR and half-life were negatively correlated, meaning that slower growing species survived for longer.5. Synthesis and applications. To advance tropical peat swamp reforestation requires expanding the number and replication of species planted and testing treatments by adopting control vs. treatment experimental designs. Species selection should involve slower growing species (e.g. Lophopetalum rigidum, Alstonia spatulata, Madhuca motleyana) that survive for longer and explore screening species based on functional traits associated with nutrient acquisition, flooding tolerance and recovery from fire.
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44.
  • Vasen, T., et al. (författare)
  • InAs nanowire GAA n-MOSFETs with 12-15 nm diameter
  • 2016
  • Ingår i: 2016 IEEE Symposium on VLSI Technology, VLSI Technology 2016. - 9781509006373 ; 2016-September
  • Konferensbidrag (refereegranskat)abstract
    • InAs nanowires (NW) grown by MOCVD with diameter d as small as 10 nm and gate-All-Around (GAA) MOSFETs with d = 12-15 nm are demonstrated. Ion = 314 μA/μm, and Ssat =68 mV/dec was achieved at Vdd = 0.5 V (Ioff = 0.1 μA/μm). Highest gm measured is 2693 μS/μm. Device performance is enabled by small diameter and optimized high-k/InAs gate stack process. Device performance tradeoffs between gm, Ron, and Imin are discussed.
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45.
  • Yeo, Leonard L L, et al. (författare)
  • Synchronous cardiocerebral infarction in the era of endovascular therapy : which to treat first?
  • 2017
  • Ingår i: Journal of Thrombosis and Thrombolysis. - : Springer Science and Business Media LLC. - 0929-5305 .- 1573-742X. ; 44:1, s. 104-111
  • Tidskriftsartikel (refereegranskat)abstract
    • A cardiocerebral ischemic attack (CCI) or a concurrent acute ischemic stroke (AIS) and myocardial infarction (AMI) is a severe event with no clear recommendations for ideal management because of the rarity of the scenario. The narrow time window for treatment and complexity of the treatment decision puts immense pressure on the treating physician. We evaluated this challenging situation at our tertiary center. Using our prospective stroke database out of a total of 555 patients with acute ischemic stroke between 2009 and 2014, we identified five consecutive cases with CCI (incidence 0.009%). Demography, risk factor characteristics, vascular occlusions and treatment approach were recorded. Good functional outcome was defined by the modified Rankin scale (mRS) score of 0-2 points. Out of five patients, AIS was treated with endovascular treatment in three cases, while two were treated with intravenous thrombolysis only. One out of three patients had embolectomy of the brain performed prior to the coronary intervention, while the other two patients underwent coronary intervention first. One patient developed sudden cardiac arrest on day-2 and passed away. CCI is an uncommon and devastating clinical scenario, further research is needed for the ideal management strategy that provides the best outcomes. However, the rarity of the disease does not lend itself to the conduct of a trial easily. We have proposed a considered treatment algorithm based on the current literature and our experience.
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