| 1. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Ademuyiwa, Adesoji O., et al.
(författare)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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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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| 3. |
- Aminoff, A, et al.
(författare)
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Allele-specific regulation of MTTP expression influences the risk of ischemic heart disease.
- 2010
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Ingår i: Journal of lipid research. - 0022-2275 .- 1539-7262. ; 51:1, s. 103-11
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Tidskriftsartikel (refereegranskat)abstract
- Promoter polymorphisms in microsomal triglyceride transfer protein (MTTP) have been associated with decreased plasma lipids but an increased risk for ischemic heart disease (IHD), indicating that MTTP influences the susceptibility for IHD independent of plasma lipids. The objective of this study was to characterize the functional promoter polymorphism in MTTP predisposing to IHD and its underlying mechanism. Use of pyrosequencing technology revealed that presence of the minor alleles of the promoter polymorphisms -493G>T and -164T>C result in lower transcription of MTTP in vivo in the heart, liver, and macrophages. In vitro experiments indicated that the minor -164C allele mediates the lower gene expression and that C/EBP binds to the polymorphic region in an allele-specific manner. Furthermore, homozygous carriers of the -164C were found to have increased risk for IHD as shown in a case-control study including a total of 544 IHD patients and 544 healthy control subjects. We concluded that carriers of the minor -164C allele have lower expression of MTTP in the heart, mediated at least partly by the transcription factor CCAAT/enhancer binding protein, and that reduced concentration of MTTP in the myocardium may contribute to IHD upon ischemic damage.
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| 4. |
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| 5. |
- Archambault, Alexi N., et al.
(författare)
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Cumulative Burden of Colorectal Cancer Associated Genetic Variants Is More Strongly Associated With Early-Onset vs Late-Onset Cancer
- 2020
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Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 158:5, s. 1274-1286.e12
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Early-onset colorectal cancer (CRC, in persons younger than 50 years old) is increasing in incidence; yet, in the absence of a family history of CRC, this population lacks harmonized recommendations for prevention. We aimed to determine whether a polygenic risk score (PRS) developed from 95 CRC-associated common genetic risk variants was associated with risk for early-onset CRC.METHODS: We studied risk for CRC associated with a weighted PRS in 12,197 participants younger than 50 years old vs 95,865 participants 50 years or older. PRS was calculated based on single nucleotide polymorphisms associated with CRC in a large-scale genome-wide association study as of January 2019. Participants were pooled from 3 large consortia that provided clinical and genotyping data: the Colon Cancer Family Registry, the Colorectal Transdisciplinary Study, and the Genetics and Epidemiology of Colorectal Cancer Consortium and were all of genetically defined European descent. Findings were replicated in an independent cohort of 72,573 participants.RESULTS: Overall associations with CRC per standard deviation of PRS were significant for early-onset cancer, and were stronger compared with late-onset cancer (P for interaction = .01); when we compared the highest PRS quartile with the lowest, risk increased 3.7-fold for early-onset CRC (95% CI 3.28-4.24) vs 2.9-fold for late-onset CRC (95% CI 2.80-3.04). This association was strongest for participants without a first-degree family history of CRC (P for interaction = 5.61 x 10(-5)). When we compared the highest with the lowest quartiles in this group, risk increased 4.3-fold for early-onset CRC (95% CI 3.61-5.01) vs 2.9-fold for late-onset CRC (95% CI 2.70-3.00). Sensitivity analyses were consistent with these findings.CONCLUSIONS: In an analysis of associations with CRC per standard deviation of PRS, we found the cumulative burden of CRC-associated common genetic variants to associate with early-onset cancer, and to be more strongly associated with early-onset than late-onset cancer, particularly in the absence of CRC family history. Analyses of PRS, along with environmental and lifestyle risk factors, might identify younger individuals who would benefit from preventive measures.
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| 6. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 7. |
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| 8. |
- Bombarda, F., et al.
(författare)
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Runaway electron beam control
- 2019
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Ingår i: Plasma Physics and Controlled Fusion. - : IOP Publishing. - 1361-6587 .- 0741-3335. ; 61:1
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Tidskriftsartikel (refereegranskat)
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| 9. |
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| 10. |
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| 11. |
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| 12. |
- Eapen, Valsamma, et al.
(författare)
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"Are you available for the next 18 months?" - methods and aims of a longitudinal birth cohort study investigating a universal developmental surveillance program: the ’Watch Me Grow’ study
- 2014
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Ingår i: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 14, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Universal developmental surveillance programs aimed at early identification and targeted early intervention significantly improve short-and long-term outcomes in children at risk of developmental disorders. However, a significant challenge remains in providing sufficiently rigorous research and robust evidence to inform policy and service delivery. This paper describes the methods of the ’Watch Me Grow’ study that aims to maximise accurate early detection of children with developmental disorders through a partnership formed between policy makers, service providers and researchers. Methods/Design: A mixed methods study design was developed consisting of: (1) a qualitative study of parents and health service providers to investigate barriers and enablers of developmental surveillance; (2) recruitment of a birth cohort and their longitudinal follow-up to 18 months of age to: a) assess risk factors for not accessing existing developmental surveillance programs and b) estimate the prevalence of children identified with developmental risk; (3) comparison of surveillance outcomes with a reference standard at 18 months of age to assess the diagnostic test accuracy of existing and alternative developmental surveillance tools; and (4) comparison of developmental surveillance models to inform policy recommendations. Data linkage will be used to determine the uptake and representativeness of the study participant group versus non-participants. Discussion: The Watch Me Grow study is expected to provide a collaborative opportunity to enhance universal developmental surveillance for early accurate identification of developmental risk. This will also provide quality evidence about identification of developmental risk and access to services to be embedded in existing practice with linkages to policy development.
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| 13. |
- Eapen, Valsamma, et al.
(författare)
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Maternal help-seeking for child developmental concerns: Associations with socio-demographic factors
- 2017
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Ingår i: Journal of Paediatrics and Child Health. - : Wiley. - 1034-4810 .- 1440-1754. ; 53, s. 963-969
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To examine socio-demographic factors associated with maternal help-seeking for child developmental concerns in a longitudinal birth cohort study. An understanding of these factors is critical to improving uptake of services to maximise early identification and intervention for developmental concerns. Methods: A birth cohort was recruited from the post-natal wards of two teaching hospitals and through community nurses in South Western Sydney, Australia, between November 2011 and April 2013. Of the 4047 mothers approached, 2025 consented to participate (response rate = 50%). Socio-demographic and service use information was collected after the child’s birth and when the child was 18 months of age. Sources of help were divided into three categories (formal health services, other formal services and informal supports) and compound variables were created by summing the number of different sources identified by mothers. Results: Significantly more sources of help were intended to be used and/or actually accessed by mothers born in Australia, whose primary language was English, with higher levels of education and annual household income, and among mothers of first-born children. Conclusions: Developmental concerns are known to increase with increased psychosocial adversity. Our findings of reduced intent to access and use of services by socio-economically disadvantaged families and those from culturally and linguistically diverse backgrounds suggests that an inverse care effect is in operation whereby those children with the greatest health needs may have the least access to services. Possible explanations for this, and recommendations for improving service accessibility for these populations through targeted and culturally appropriate services, are discussed. Copyright © 2017 Paediatrics and Child Health Division (The Royal Australasian College of Physicians)
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| 14. |
- Ekstrand, Elisabeth, et al.
(författare)
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Clinical interpretation and cutoff scores for manual ability measured by the ABILHAND questionnaire in people with stroke.
- 2023
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Ingår i: Topics in stroke rehabilitation. - : Informa UK Limited. - 1945-5119 .- 1074-9357. ; 30:1, s. 21-31
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Tidskriftsartikel (refereegranskat)abstract
- The ABILHAND questionnaire is recommended to assess perceived manual ability after stroke; however, more knowledge on interpretability is needed to improve the clinical applicability.To determine clinically meaningful cutoff scores for different levels of perceived manual ability, assessed by ABILHAND, corresponding to established observed and perceived upper extremity assessments post stroke.This cross-sectional study, part of the Stroke Arm Longitudinal Study (SALGOT) at the University of Gothenburg, included 80 participants with upper extremity impairments after stroke. The self-reported upper extremity functioning was assessed with ABILHAND and Stroke Impact Scale Hand (SIS Hand), and the observed functioning was assessed by Fugl-Meyer Assessment for Upper Extremity (FMA-UE) and Action Research Arm Test (ARAT) at 3months after stroke. Receiver operating characteristic curve, sensitivity, and specificity analyses were used to determine the cutoffs.The overall discriminating accuracy was excellent (AUC > 0.90) for most of the cutoffs and sensitivity and specificity values ranged from 0.73 to 1.0. The ABILHAND cutoff score 1.78 discriminated well between low and good functioning resulting in a 95% match with SIS Hand and 87.5% match with ARAT and FMA-UE.The determined cutoff scores of the ABILHAND, validated through established upper extremity assessments, will provide a useful tool to clinicians when interpreting the logit scores and when selecting individualized treatment options. ABILHAND matched well with self-reported SIS Hand, but discrepancies found with observed scales implies that self-perceived assessments should be complemented with observed assessments.
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| 15. |
- Ekstrand, Elisabeth, et al.
(författare)
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Longitudinal changes of self-perceived manual ability the first year after stroke : A cohort study
- 2020
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Ingår i: BMC Neurology. - : Springer Science and Business Media LLC. - 1471-2377. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Recovery patterns of motor function and activity capacity of the upper extremity after stroke have been described, but less is known about longitudinal changes of perceived manual activity performance. The aim of this study was to investigate longitudinal changes of self-perceived manual ability at several timepoints from onset until 12 months post-stroke in a cohort of consecutively recruited individuals with mild, moderate and severe stroke. Methods: The study included 106 participants from a non-selected cohort with first-ever mild, moderate or severe stroke and impaired upper extremity function (Stroke Arm Longitudinal Study at the University of Gothenburg, SALGOT). Self-perceived manual ability was assessed with the ABILHAND Questionnaire at 3 and 10 days, 4 weeks, 3, 6 and 12 months after stroke. Longitudinal change was assessed by linear mixed models (fixed and random effects) and adjusted models were built by adding effects of cofactors age, gender, stroke severity, living condition and affected hand. Results: Self-perceived manual ability increased over time the first year after stroke for the total group and the subgroups. The final adjusted model for the total group included fix-effects of time (expected mean change 0.24 logits per month) adjusted by age (-0.06 per year) and stroke severity (-0.19 per NIHSS-score). In addition to significant effect of time, the adjusted models for moderate stroke subgroup included fixed effect of age, and for mild and severe subgroups there was an interaction effect between time and age. Further analyses between time-points showed that no significant change of self-perceived manual ability was detected beyond 3 months post-stroke. Conclusions: Self-perceived manual ability increased over time the first year after stroke, and this change was to some degree modulated by age and stroke severity at onset. Most of the improvements occurred early, predominantly within the first three months after stroke.
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| 16. |
- Ekstrand, Elisabeth, et al.
(författare)
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Which clinical and sociodemographic determinants are associated with self-perceived manual ability at one year after stroke?
- 2020
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Ingår i: Disability and Rehabilitation. - : Informa UK Limited. - 0963-8288 .- 1464-5165. ; 42:16, s. 2279-2286
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To evaluate the impact of multiple potential sociodemographic and clinical stroke-related determinants on self-perceived manual ability in an unselected sample of individuals 12 months after first-ever stroke. Methods: A cross-sectional sample of 68 participants (mean age 66) with UE impairments were followed up at 12 months post stroke. Stroke severity at onset was moderate for the majority. Manual ability was assessed by the patient-reported outcome measure ABILHAND Questionnaire. Determinants included in the multivariate regression analysis were age, gender, living situation, vocational situation, affected hand, stroke severity at onset and UE disability (motor function, sensory function, joint motion, pain, grip strength, spasticity and activity capacity) at 12 months post stroke. Results: The strongest associated determinants with self-perceived manual ability were UE motor function and UE activity capacity at 12 months post-stroke. UE motor function together with age and grip strength explained 65% of the variance in one final multivariate model. UE activity capacity and grip strength explained 62% of the variance in a second final model. Conclusion: In order to understand self-perceived difficulties in manual ability in daily activities in persons with stroke, assessments of UE motor function and activity capacity are recommended. Implications for rehabilitation The ultimate goal of the upper extremity rehabilitation after stroke is to regain ability to use the UE in daily activities that are important to the individual in his or her own environment. This requires a good understanding of factors that are associated with self-perceived manual ability in order to tailor effective rehabilitation interventions. Upper extremity motor function and activity capacity are the strongest determinants associated with self-perceived manual ability one year after stroke. These factors are recommended to be included in the assessment battery in stroke to fully understand the disability in daily life.
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| 17. |
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| 18. |
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| 19. |
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| 20. |
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| 21. |
- Joffrin, E., et al.
(författare)
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Overview of the JET preparation for deuterium-tritium operation with the ITER like-wall
- 2019
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 59:11
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Forskningsöversikt (refereegranskat)abstract
- For the past several years, the JET scientific programme (Pamela et al 2007 Fusion Eng. Des. 82 590) has been engaged in a multi-campaign effort, including experiments in D, H and T, leading up to 2020 and the first experiments with 50%/50% D-T mixtures since 1997 and the first ever D-T plasmas with the ITER mix of plasma-facing component materials. For this purpose, a concerted physics and technology programme was launched with a view to prepare the D-T campaign (DTE2). This paper addresses the key elements developed by the JET programme directly contributing to the D-T preparation. This intense preparation includes the review of the physics basis for the D-T operational scenarios, including the fusion power predictions through first principle and integrated modelling, and the impact of isotopes in the operation and physics of D-T plasmas (thermal and particle transport, high confinement mode (H-mode) access, Be and W erosion, fuel recovery, etc). This effort also requires improving several aspects of plasma operation for DTE2, such as real time control schemes, heat load control, disruption avoidance and a mitigation system (including the installation of a new shattered pellet injector), novel ion cyclotron resonance heating schemes (such as the three-ions scheme), new diagnostics (neutron camera and spectrometer, active Alfven eigenmode antennas, neutral gauges, radiation hard imaging systems...) and the calibration of the JET neutron diagnostics at 14 MeV for accurate fusion power measurement. The active preparation of JET for the 2020 D-T campaign provides an incomparable source of information and a basis for the future D-T operation of ITER, and it is also foreseen that a large number of key physics issues will be addressed in support of burning plasmas.
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| 22. |
- Kalinowski, A., et al.
(författare)
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Evaluation of C4 gene copy number in Pediatric Acute Neuropsychiatric Syndrome
- 2023
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Ingår i: Developmental Neuroscience. - 0378-5866. ; 45:6, s. 315-324
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Tidskriftsartikel (refereegranskat)abstract
- Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) is an abrupt-onset neuropsychiatric disorder. PANS patients have an increased prevalence of co-morbid autoimmune illness, most commonly arthritis. In addition, an estimated one-third of PANS patients present with low serum C4 protein, suggesting decreased production or increased consumption of C4 protein. To test the possibility that copy number (CN) variation contributes to risk of PANS illness, we compared mean total C4A and total C4B CN in ethnically-matched subjects from PANS DNA samples and controls (192 cases and 182 controls). Longitudinal data from the Stanford PANS cohort (n = 121) was used to assess whether the time to Juvenile Idiopathic Arthritis (JIA) or Autoimmune Disease (AI) onset was a function of total C4A or C4B. Lastly, we performed several hypothesis-generating analyses to explore the correlation between individual C4 gene variants, sex, specific genotypes and age of PANS onset. Although the mean total C4A or C4B CN did not differ in PANS compared to controls, PANS patients with low C4B CN were at increased risk for subsequent JIA diagnosis (Hazard Ratio = 2 7, p-value = 0 004). We also observed a possible increase in risk for AI in PANS patients and a possible correlation between lower C4B and PANS age of onset. An association between rheumatoid arthritis and low C4B CN has been reported previously. However, patients with PANS develop different types of JIA: enthesitis-related arthritis, spondyloarthritis and psoriatic arthritis. This suggests that C4B plays a role that spans these arthritis types.
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| 23. |
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| 24. |
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| 25. |
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| 26. |
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| 27. |
- Marchi, Mattia, et al.
(författare)
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Experience of discrimination during COVID-19 pandemic : the impact of public health measures and psychological distress among refugees and other migrants in Europe
- 2022
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Ingår i: BMC Public Health. - : Springer Nature. - 1471-2458. ; 22
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Tidskriftsartikel (refereegranskat)abstract
- Background: The COVID-19 pandemic has had a disproportionately hard impact on refugees and other migrants who are often exposed to the virus with limited means to protect themselves. We tested the hypothesis that during the COVID-19 pandemic, refugees and other migrants have suffered a negative impact on mental health and have been unjustly discriminated for spreading the disease in Europe (data collection from April to November 2020).Methods: Participants in the ApartTogether Survey (N = 8297, after listwise deletion of missing items final N = 3940) provided data regarding to their difficulties to adhere to preventive recommendations against COVID-19 infection (CARE), self-perceived stigmatization (SS), and psychological distress (PD). Structural Equation Modeling was used to investigate PD as a mediator in the pathway linking CARE to SS, while adjusting for the housing and residence status. To improve confidence in the findings, single hold-out sample cross-validation was performed using a train/test split ratio of 0.8/0.2.Results: In the exploratory set (N = 3159) SS was associated with both CARE (B = 0.200, p < 0.001) and PD (B = 0.455, p < 0.001). Moreover, PD was also associated with CARE (B = 0.094, p = 0.001) and mediated the effect of CARE on SS (proportion mediated = 17.7%, p = 0.001). The results were successfully replicated in the confirmation set (N = 781; total effect = 0.417, p < 0.001; proportion mediated = 29.7%, p < 0.001). Follow-up analyses also found evidence for an opposite effect (i.e., from SS to CARE, B = 0.132; p < 0.001), suggesting that there might be a vicious circle between the self-perceived stigmatization and the access to health care and the use of preventive measures against COVID-19 infection.Conclusions: Refugees and other migrants who had more difficulties in accessing health care and preventive measures against COVID-19 infection experienced worse mental health and increased discrimination. These negative effects appeared to be stronger for those with more insecure housing and residence status, highlighting from one side the specific risk of insecure housing in the impact of COVID-19 upon mental health and infection protection, and for another side the need to proper housing as a strategy to prevent both COVID-19 and mental distress.
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| 28. |
- Minelli, Caterina, et al.
(författare)
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Versailles project on advanced materials and standards (VAMAS) interlaboratory study on measuring the number concentration of colloidal gold nanoparticles
- 2022
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Ingår i: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3372 .- 2040-3364. ; 14, s. 4690-4704
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Tidskriftsartikel (refereegranskat)abstract
- We describe the outcome of a large international interlaboratory study of the measurement of particle number concentration of colloidal nanoparticles, project 10 of the technical working area 34, "Nanoparticle Populations" of the Versailles Project on Advanced Materials and Standards (VAMAS). A total of 50 laboratories delivered results for the number concentration of 30 nm gold colloidal nanoparticles measured using particle tracking analysis (PTA), single particle inductively coupled plasma mass spectrometry (spICP-MS), ultraviolet-visible (UV-Vis) light spectroscopy, centrifugal liquid sedimentation (CLS) and small angle X-ray scattering (SAXS). The study provides quantitative data to evaluate the repeatability of these methods and their reproducibility in the measurement of number concentration of model nanoparticle systems following a common measurement protocol. We find that the population-averaging methods of SAXS, CLS and UV-Vis have high measurement repeatability and reproducibility, with between-labs variability of 2.6%, 11% and 1.4% respectively. However, results may be significantly biased for reasons including inaccurate material properties whose values are used to compute the number concentration. Particle-counting method results are less reproducibile than population-averaging methods, with measured between-labs variability of 68% and 46% for PTA and spICP-MS respectively. This study provides the stakeholder community with important comparative data to underpin measurement reproducibility and method validation for number concentration of nanoparticles.
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| 29. |
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| 30. |
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| 31. |
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| 32. |
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| 33. |
- Richards, Stephen, et al.
(författare)
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Genome Sequence of the Pea Aphid Acyrthosiphon pisum
- 2010
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Ingår i: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 8:2, s. e1000313-
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Tidskriftsartikel (refereegranskat)abstract
- Aphids are important agricultural pests and also biological models for studies of insect-plant interactions, symbiosis, virus vectoring, and the developmental causes of extreme phenotypic plasticity. Here we present the 464 Mb draft genome assembly of the pea aphid Acyrthosiphon pisum. This first published whole genome sequence of a basal hemimetabolous insect provides an outgroup to the multiple published genomes of holometabolous insects. Pea aphids are host-plant specialists, they can reproduce both sexually and asexually, and they have coevolved with an obligate bacterial symbiont. Here we highlight findings from whole genome analysis that may be related to these unusual biological features. These findings include discovery of extensive gene duplication in more than 2000 gene families as well as loss of evolutionarily conserved genes. Gene family expansions relative to other published genomes include genes involved in chromatin modification, miRNA synthesis, and sugar transport. Gene losses include genes central to the IMD immune pathway, selenoprotein utilization, purine salvage, and the entire urea cycle. The pea aphid genome reveals that only a limited number of genes have been acquired from bacteria; thus the reduced gene count of Buchnera does not reflect gene transfer to the host genome. The inventory of metabolic genes in the pea aphid genome suggests that there is extensive metabolite exchange between the aphid and Buchnera, including sharing of amino acid biosynthesis between the aphid and Buchnera. The pea aphid genome provides a foundation for post-genomic studies of fundamental biological questions and applied agricultural problems.
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| 34. |
- Roberts, Jason D., et al.
(författare)
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Ankyrin-B dysfunction predisposes to arrhythmogenic cardiomyopathy and is amenable to therapy
- 2019
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Ingår i: Journal of Clinical Investigation. - : AMER SOC CLINICAL INVESTIGATION INC. - 0021-9738 .- 1558-8238. ; 129:8, s. 3171-3184
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Tidskriftsartikel (refereegranskat)abstract
- Arrhythmogenic cardiomyopathy (ACM) is an inherited arrhythmia syndrome characterized by severe structural and electrical cardiac phenotypes, including myocardial fibrofatty replacement and sudden cardiac death. Clinical management of ACM is largely palliative, owing to an absence of therapies that target its underlying pathophysiology, which stems partially from our limited insight into the condition. Following identification of deceased ACM probands possessing ANK2 rare variants and evidence of ankyrin-B loss of function on cardiac tissue analysis, an ANK2 mouse model was found to develop dramatic structural abnormalities reflective of human ACM, including biventricular dilation, reduced ejection fraction, cardiac fibrosis, and premature death. Desmosomal structure and function appeared preserved in diseased human and murine specimens in the presence of markedly abnormal beta-catenin expression and patterning, leading to identification of a previously unknown interaction between ankyrin-B and beta-catenin. A pharmacological activator of the WNT/beta-catenin pathway, SB-216763, successfully prevented and partially reversed the murine ACM phenotypes. Our findings introduce what we believe to be a new pathway for ACM, a role of ankyrin-B in cardiac structure and signaling, a molecular link between ankyrin-B and beta-catenin, and evidence for targeted activation of the WNT/beta-catenin pathway as a potential treatment for this disease.
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| 35. |
- Sohn, Robert A., et al.
(författare)
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Explosive volcanism on the ultraslow-spreading Gakkel ridge, Arctic Ocean
- 2008
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 453:7199, s. 1236-1238
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Tidskriftsartikel (refereegranskat)abstract
- Roughly 60% of the Earth's outer surface is composed of oceanic crust formed by volcanic processes at mid-ocean ridges. Although only a small fraction of this vast volcanic terrain has been visually surveyed or sampled, the available evidence suggests that explosive eruptions are rare on mid-ocean ridges, particularly at depths below the critical point for seawater (3,000 m)1. A pyroclastic deposit has never been observed on the sea floor below 3,000 m, presumably because the volatile content of mid-ocean-ridge basalts is generally too low to produce the gas fractions required for fragmenting a magma at such high hydrostatic pressure. We employed new deep submergence technologies during an International Polar Year expedition to the Gakkel ridge in the Arctic Basin at 85° E, to acquire photographic and video images of 'zero-age' volcanic terrain on this remote, ice-covered ridge. Here we present images revealing that the axial valley at 4,000 m water depth is blanketed with unconsolidated pyroclastic deposits, including bubble wall fragments (limu o Pele)2, covering a large (>10 km2) area. At least 13.5 wt% CO2 is necessary to fragment magma at these depths3, which is about tenfold the highest values previously measured in a mid-ocean-ridge basalt4. These observations raise important questions about the accumulation and discharge of magmatic volatiles at ultraslow spreading rates on the Gakkel ridge5 and demonstrate that large-scale pyroclastic activity is possible along even the deepest portions of the global mid-ocean ridge volcanic system.
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| 36. |
- Spiritus-Beerden, Eva, et al.
(författare)
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Mental Health of Refugees and Migrants during the COVID-19 Pandemic : The Role of Experienced Discrimination and Daily Stressors
- 2021
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 18:12
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Tidskriftsartikel (refereegranskat)abstract
- The COVID-19 pandemic is a defining global health crisis of our time. While the impact of COVID-19, including its mental health impact, is increasingly being documented, there remain important gaps regarding the specific consequences of the pandemic on particular population groups, including refugees and migrants. This study aims to uncover the impact of the COVID-19 pandemic on the mental health of refugees and migrants worldwide, disentangling the possible role of social and daily stressors, i.e., experiences of discrimination and daily living conditions. Descriptive analysis and structural equation modeling were used to analyze the responses of N = 20,742 refugees and migrants on the self-reporting global ApartTogether survey. Survey findings indicated that the mental health of refugees and migrants during the COVID-19 pandemic was significantly impacted, particularly for certain subgroups, (i.e., insecure housing situation and residence status, older respondents, and females) who reported experiencing higher levels of increased discrimination and increases in daily life stressors. There is a need to recognize the detrimental mental health impact of the COVID-19 pandemic on particular refugee and migrant groups and to develop interventions that target their unique needs.
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| 38. |
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| 39. |
- Thomas, Minta, et al.
(författare)
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Combining Asian and European genome-wide association studies of colorectal cancer improves risk prediction across racial and ethnic populations
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Polygenic risk scores (PRS) have great potential to guide precision colorectal cancer (CRC) prevention by identifying those at higher risk to undertake targeted screening. However, current PRS using European ancestry data have sub-optimal performance in non-European ancestry populations, limiting their utility among these populations. Towards addressing this deficiency, we expand PRS development for CRC by incorporating Asian ancestry data (21,731 cases; 47,444 controls) into European ancestry training datasets (78,473 cases; 107,143 controls). The AUC estimates (95% CI) of PRS are 0.63(0.62-0.64), 0.59(0.57-0.61), 0.62(0.60-0.63), and 0.65(0.63-0.66) in independent datasets including 1681-3651 cases and 8696-115,105 controls of Asian, Black/African American, Latinx/Hispanic, and non-Hispanic White, respectively. They are significantly better than the European-centric PRS in all four major US racial and ethnic groups (p-values < 0.05). Further inclusion of non-European ancestry populations, especially Black/African American and Latinx/Hispanic, is needed to improve the risk prediction and enhance equity in applying PRS in clinical practice.
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| 40. |
- Thomas, Minta, et al.
(författare)
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Genome-wide Modeling of Polygenic Risk Score in Colorectal Cancer Risk.
- 2020
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Ingår i: American Journal of Human Genetics. - Cambridge : Elsevier BV. - 0002-9297 .- 1537-6605. ; 107:3, s. 432-444
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Tidskriftsartikel (refereegranskat)abstract
- Accurate colorectal cancer (CRC) risk prediction models are critical for identifying individuals at low and high risk of developing CRC, as they can then be offered targeted screening and interventions to address their risks of developing disease (if they are in a high-risk group) and avoid unnecessary screening and interventions (if they are in a low-risk group). As it is likely that thousands of genetic variants contribute to CRC risk, it is clinically important to investigate whether these genetic variants can be used jointly for CRC risk prediction. In this paper, we derived and compared different approaches to generating predictive polygenic risk scores (PRS) from genome-wide association studies (GWASs) including 55,105 CRC-affected case subjects and 65,079 control subjects of European ancestry. We built the PRS in three ways, using (1) 140 previously identified and validated CRC loci; (2) SNP selection based on linkage disequilibrium (LD) clumping followed by machine-learning approaches; and (3) LDpred, a Bayesian approach for genome-wide risk prediction. We tested the PRS in an independent cohort of 101,987 individuals with 1,699 CRC-affected case subjects. The discriminatory accuracy, calculated by the age- and sex-adjusted area under the receiver operating characteristics curve (AUC), was highest for the LDpred-derived PRS (AUC = 0.654) including nearly 1.2 M genetic variants (the proportion of causal genetic variants for CRC assumed to be 0.003), whereas the PRS of the 140 known variants identified from GWASs had the lowest AUC (AUC = 0.629). Based on the LDpred-derived PRS, we are able to identify 30% of individuals without a family history as having risk for CRC similar to those with a family history of CRC, whereas the PRS based on known GWAS variants identified only top 10% as having a similar relative risk. About 90% of these individuals have no family history and would have been considered average risk under current screening guidelines, but might benefit from earlier screening. The developed PRS offers a way for risk-stratified CRC screening and other targeted interventions.
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| 41. |
- Thomas, Minta, et al.
(författare)
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Response to Li and Hopper
- 2021
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 108:3, s. 527-529
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Tidskriftsartikel (refereegranskat)
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| 42. |
- Trichopoulos, Dimitrios, et al.
(författare)
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Hepatocellular carcinoma risk factors and disease burden in a European cohort : a nested case-control study
- 2011
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Ingår i: Journal of the National Cancer Institute. - Oxford : Oxford University Press. - 0027-8874 .- 1460-2105. ; 103:22, s. 1686-1695
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Tidskriftsartikel (refereegranskat)abstract
- Background: To date, no attempt has been made to systematically determine the apportionment of the hepatocellular carcinoma burden in Europe or North America among established risk factors.Methods: Using data collected from 1992 to 2006, which included 4 409 809 person-years in the European Prospective Investigation into Cancer and nutrition (EPIC), we identified 125 case patients with hepatocellular carcinoma, of whom 115 were matched to 229 control subjects. We calculated odds ratios (ORs) for the association of documented risk factors for hepatocellular carcinoma with incidence of this disease and estimated their importance in this European cohort.Results: Chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (OR = 9.10, 95% confidence interval [CI] = 2.10 to 39.50 and OR = 13.36, 95% CI = 4.11 to 43.45, respectively), obesity (OR = 2.13, 95% CI = 1.06 to 4.29), former or current smoking (OR = 1.98, 95% CI = 0.90 to 4.39 and OR = 4.55, 95% CI = 1.90 to 10.91, respectively), and heavy alcohol intake (OR = 1.77, 95% CI = 0.73 to 4.27) were associated with hepatocellular carcinoma. Smoking contributed to almost half of all hepatocellular carcinomas (47.6%), whereas 13.2% and 20.9% were attributable to chronic HBV and HCV infection, respectively. Obesity and heavy alcohol intake contributed 16.1% and 10.2%, respectively. Almost two-thirds (65.7%, 95% CI = 50.6% to 79.3%) of hepatocellular carcinomas can be accounted for by exposure to at least one of these documented risk factors.Conclusions: Smoking contributed to more hepatocellular carcinomas in this Europe-wide cohort than chronic HBV and HCV infections. Heavy alcohol consumption and obesity also contributed to sizeable fractions of this disease burden. These contributions may be underestimates because EPIC volunteers are likely to be more health conscious than the general population.
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| 43. |
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| 44. |
- Werren, John H, et al.
(författare)
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Functional and evolutionary insights from the genomes of three parasitoid Nasonia species.
- 2010
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 327:5963, s. 343-8
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Tidskriftsartikel (refereegranskat)abstract
- We report here genome sequences and comparative analyses of three closely related parasitoid wasps: Nasonia vitripennis, N. giraulti, and N. longicornis. Parasitoids are important regulators of arthropod populations, including major agricultural pests and disease vectors, and Nasonia is an emerging genetic model, particularly for evolutionary and developmental genetics. Key findings include the identification of a functional DNA methylation tool kit; hymenopteran-specific genes including diverse venoms; lateral gene transfers among Pox viruses, Wolbachia, and Nasonia; and the rapid evolution of genes involved in nuclear-mitochondrial interactions that are implicated in speciation. Newly developed genome resources advance Nasonia for genetic research, accelerate mapping and cloning of quantitative trait loci, and will ultimately provide tools and knowledge for further increasing the utility of parasitoids as pest insect-control agents.
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| 45. |
- Woolfenden, Susan, et al.
(författare)
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Prevalence and factors associated with parental concerns about development detected by the Parents’ Evaluation of Developmental Status (PEDS) at 6-month, 12-month and 18-month well-child checks in a birth cohort
- 2016
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Early identification of developmental vulnerability is vital. This study aimed to estimate the prevalence of moderate or high developmental risk on the Parents’ Evaluation of Developmental Status (PEDS) at 6-month, 12-month and 18-month well-child checks; identify associated risk factors; and examine documentation of the PEDS at well-child checks. Design, participants: A prospective birth cohort of 2025 children with 50% of those approached agreeing to participate. Demographic data were obtained via questionnaires and linked electronic medical records. Telephone interviews were conducted with parents to collect PEDS data. Primary and secondary outcomes: Multiple logistic regression analyses identified risk factors for moderate or high developmental risk on the PEDS. A Cumulative Risk Index examined the impact of multiple risk factors on developmental risk and documentation of the PEDS at the well-child checks. Results: Of the original cohort, 792 (39%) had 6-month, 649 (32%) had 12-month and 565 (28%) had 18-month PEDS data. Parental concerns indicating moderate or high developmental risk on the PEDS were 27% (95% CI 24 to 30) at 6 months, 27% (95% CI 24 to 30) at 12 months and 33% (95% CI 29 to 37) at 18 months. Factors associated with moderate or high developmental risk were perinatal risk (OR 12 months: 1.7 (95% CI 1.1 to 2.7)); maternal Middle Eastern or Asian nationality (OR 6 months: 1.6 (95% CI 1.1 to 2.4)), (OR 12 months: 1.7 (95% CI 1.1 to 2.7)); and household disadvantage (OR 6 months: 1.5 (95% CI 1.0 to 2.2). As the number of risk factors increased the odds increased for high or moderate developmental risk and no documentation of the PEDS at well-child checks. Conclusions: Children with multiple risk factors are more likely to have parental concerns indicating developmental vulnerability using the PEDS and for these concerns to not be documented.
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| 46. |
- Woolfenden, Susan, et al.
(författare)
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Who is our cohort: : recruitment, representativeness, baseline risk and retention in the 'Watch Me Grow' study?
- 2016
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Ingår i: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND The "Watch Me Grow" (WMG) study examines the current developmental surveillance system in South West Sydney. This paper describes the establishment of the study birth cohort, including the recruitment processes, representativeness, follow-up and participants’ baseline risk for future developmental risk. METHODS Newborn infants and their parents were recruited from two public hospital postnatal wards and through child health nurses during the years 2011-2013. Data was obtained through a detailed participant questionnaire and linked with the participant’s electronic medical record (EMR). Representativeness was determined by Chi-square analyses of the available clinical, psychosocial and sociodemographic EMR data, comparing the WMG participants to eligible non-participants. Reasons for non-participation were also elicited. Participant characteristics were examined in six, 12, and 18-month follow-ups. RESULTS The number of infants recruited totalled 2,025, with 50 % of those approached agreeing to participate. Reasons for parents not participating included: lack of interest, being too busy, having plans to relocate, language barriers, participation in other research projects, and privacy concerns. The WMG cohort was broadly representative of the culturally diverse and socially disadvantaged local population from which it was sampled. Of the original 2025 participants enrolled at birth, participants with PEDS outcome data available at follow-up were: 792 (39 %) at six months, 649 (32 %) at 12 months, and 565 (28 %) at 18 months. Participants with greater psychosocial risk were less likely to have follow-up outcome data. Almost 40 % of infants in the baseline cohort were exposed to at least two risk factors known to be associated with developmental risk. CONCLUSIONS The WMG study birth cohort is a valuable resource for health services due to the inclusion of participants from vulnerable populations, despite there being challenges in being able to actively follow-up this population.
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| 47. |
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- 2018
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 58:9
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Tidskriftsartikel (refereegranskat)
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| 48. |
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- 2018
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 58:1
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Forskningsöversikt (refereegranskat)
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