| 1. |
- Clement, Yves, et al.
(författare)
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Evolutionary forces affecting synonymous variations in plant genomes
- 2017
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Ingår i: PLOS Genetics. - : PUBLIC LIBRARY SCIENCE. - 1553-7390 .- 1553-7404. ; 13:5
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Tidskriftsartikel (refereegranskat)abstract
- Base composition is highly variable among and within plant genomes, especially at third codon positions, ranging from GC-poor and homogeneous species to GC-rich and highly heterogeneous ones (particularly Monocots). Consequently, synonymous codon usage is biased in most species, even when base composition is relatively homogeneous. The causes of these variations are still under debate, with three main forces being possibly involved: mutational bias, selection and GC-biased gene conversion (gBGC). So far, both selection and gBGC have been detected in some species but how their relative strength varies among and within species remains unclear. Population genetics approaches allow to jointly estimating the intensity of selection, gBGC and mutational bias. We extended a recently developed method and applied it to a large population genomic dataset based on transcriptome sequencing of 11 angiosperm species spread across the phylogeny. We found that at synonymous positions, base composition is far from mutation-drift equilibrium in most genomes and that gBGC is a widespread and stronger process than selection. gBGC could strongly contribute to base composition variation among plant species, implying that it should be taken into account in plant genome analyses, especially for GC-rich ones.
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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. |
- Coley, Nicola, et al.
(författare)
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Plasma p-tau181 as an outcome and predictor of multidomain intervention effects: a secondary analysis of a randomised, controlled, dementia prevention trial
- 2024
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Ingår i: The Lancet Healthy Longevity. - 2666-7568. ; 5:2
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Tidskriftsartikel (refereegranskat)abstract
- Background: It is unknown whether multidomain interventions, which might preserve late-life cognition, affect Alzheimer's disease pathology. Previous studies measured cerebrospinal fluid and imaging Alzheimer's disease biomarkers in small subsamples of multidomain trial participants. Newly developed assays enable the measurement of blood-based Alzheimer's disease biomarkers in larger samples. We aimed to assess whether plasma tau phosphorylated at threonine 181 (p-tau181) was able to detect or predict 3-year multidomain intervention effects. Methods: This is a secondary analysis of the randomised, controlled, Multidomain Alzheimer Prevention Trial (MAPT) testing a 3-year multidomain intervention, omega-3 fatty acid supplementation, or both versus placebo, in individuals aged 70 years and older in 13 memory centres in France and Monaco. Plasma p-tau181 was measured in stored blood samples in a subsample of 527 participants on an intention-to-treat basis. Changes in cognitive score were calculated as a composite measure using the average of Z scores for the following tests: Mini Mental State Examination orientation items, Free and Cued Selective Reminding Test (sum of free and total recall scores), category fluency, and Digit Symbol Substitution Test. Intervention effects on 3-year change in p-tau181 concentration were estimated by use of a linear mixed model with centre-specific random intercepts. Findings: Recruitment took place between May 30, 2008, and Feb 24, 2011. Median baseline plasma p-tau181 was 8·8 pg/mL (IQR 6·7–11·9) in the total sample, and significantly higher in older individuals, men, APOE ε4 carriers, and participants with renal dysfunction or a positive PET amyloid scan. During 3-year follow-up, individuals with raised baseline p-tau181 underwent greater cognitive decline (eg, mean difference in 3-year change on the composite cognitive score between control group participants with normal and abnormal baseline levels of p-tau was −0·34 [effect size −0·52; 95% CI −0·61 to 0·07] in the fully adjusted model using a 12·4 pg/mL cutoff for abnormal baseline p-tau181), but there were no intervention effects on change in p-tau181 either in this subgroup or the total population, and no effect on cognitive change in individuals with raised baseline p-tau181 (eg, in the fully adjusted model using the 12·4 pg/mL cutoff for p-tau181 abnormality, the mean difference [95% CI] in this subgroup in 3-year decline on the composite cognitive score between the control group and the multidomain + omega-3 group, the omega-3 group, and the multidomain intervention group, was, respectively: 0·13 [−0·21 to 0·47], 0·03 [−0·30 to 0·36], and 0·10 [−0·26 to 0·46]). Surprisingly, individuals with raised baseline p-tau181 showed a decrease in p-tau181 during follow-up (eg, unadjusted mean [95% CI] 3-year change was −3·01 pg/mL (−4·45 to −1·56) in control group subjects with abnormal baseline p-tau181 [using the 12·4 pg/mL abnormal p-tau cutoff]). Interpretation: Our results support the utility of p-tau181 as a prognostic biomarker, but it did not predict or detect intervention effects in this study. Further investigation of its usefulness as a prevention trial outcome measure is required.
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| 4. |
- Descatha, Alexis, et al.
(författare)
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The effect of exposure to long working hours on stroke : A systematic review and meta-analysis from the WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury
- 2020
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 142
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Forskningsöversikt (refereegranskat)abstract
- Background: The World Health Organization (WHO) and the International Labour Organization (ILO) are developing joint estimates of the work-related burden of disease and injury (WHO/ILO Joint Estimates), with contributions from a large network of individual experts. Evidence from mechanistic data and prior studies suggests that exposure to long working hours may cause stroke. In this paper, we present a systematic review and meta-analysis of parameters for estimating the number of deaths and disability-adjusted life years from stroke that are attributable to exposure to long working hours, for the development of the WHO/ILO Joint Estimates.Objectives: We aimed to systematically review and meta-analyse estimates of the effect of exposure to long working hours (three categories: 41-48, 49-54 and >= 55 h/week), compared with exposure to standard working hours (35-40 h/week), on stroke (three outcomes: prevalence, incidence, and mortality).Data sources: A protocol was developed and published, applying the Navigation Guide to systematic reviews as an organizing framework where feasible. We searched electronic databases for potentially relevant records from published and unpublished studies, including Ovid MEDLINE, PubMed, EMBASE, Scopus, Web of Science, CISDOC, PsycINFO, and WHO ICTRP. We also searched grey literature databases, Internet search engines, and organizational websites; hand-searched reference lists of previous systematic reviews; and consulted additional experts.Study eligibility and criteria: We included working-age (>= 15 years) individuals in the formal and informal economy in any WHO and/or ILO Member State but excluded children (aged < 15 years) and unpaid domestic workers. We included randomized controlled trials, cohort studies, case-control studies and other non-randomized intervention studies with an estimate of the effect of exposure to long working hours (41-48, 49-54 and >= 55 h/week), compared with exposure to standard working hours (35-40 h/week), on stroke (prevalence, incidence or mortality).Study appraisal and synthesis methods: At least two review authors independently screened titles and abstracts against the eligibility criteria at a first review stage and full texts of potentially eligible records at a second stage, followed by extraction of data from qualifying studies. Missing data were requested from principal study authors. We combined relative risks using random-effects meta-analysis. Two or more review authors assessed the risk of bias, quality of evidence and strength of evidence, using the Navigation Guide and GRADE tools and approaches adapted to this project.Results: Twenty-two studies (20 cohort studies, 2 case-control studies) met the inclusion criteria, comprising a total of 839,680 participants (364,616 females) in eight countries from three WHO regions (Americas, Europe, and Western Pacific). The exposure was measured using self-reports in all studies, and the outcome was assessed with administrative health records (13 studies), self-reported physician diagnosis (7 studies), direct diagnosis by a physician (1 study) or during a medical interview (1 study). The outcome was defined as an incident non-fatal stroke event in nine studies (7 cohort studies, 2 case-control studies), incident fatal stroke event in one cohort study and incident non-fatal or fatal (mixed) event in 12 studies (all cohort studies). Cohort studies were judged to have a relatively low risk of bias; therefore, we prioritized evidence from these studies, but synthesised evidence from case-control studies as supporting evidence. For the bodies of evidence for both outcomes with any eligible studies (i.e. stroke incidence and mortality), we did not have serious concerns for risk of bias (at least for the cohort studies). Eligible studies were found on the effects of long working hours on stroke incidence and mortality, but not prevalence. Compared with working 35-40 h/week, we were uncertain about the effect on incidence of stroke due to working 41-48 h/week (relative risk (RR) 1.04, 95% confidence interval (CI) 0.94-1.14, 18 studies, 277,202 participants, I-2 0%, low quality of evidence). There may have been an increased risk for acquiring stroke when working 49-54 h/week compared with 35-40 h/week (RR 1.13, 95% CI 1.00-1.28, 17 studies, 275,181participants, I-2 0%, p 0.04, moderate quality of evidence). Compared with working 35-40 h/week, working >= 55 h/week may have led to a moderate, clinically meaningful increase in the risk of acquiring stroke, when followed up between one year and 20 years (RR 1.35, 95% CI 1.13 to 1.61, 7 studies, 162,644 participants, I-2 3%, moderate quality of evidence). Compared with working 35-40 h/week, we were very uncertain about the effect on dying (mortality) of stroke due to working 41-48 h/week (RR 1.01, 95% CI 0.91-1.12, 12 studies, 265,937 participants, I-2 0%, low quality of evidence), 49-54 h/week (RR 1.13, 95% CI 0.99-1.29, 11 studies, 256,129 participants, I-2 0%, low quality of evidence) and 55 h/week (RR 1.08, 95% CI 0.89-1.31, 10 studies, 664,647 participants, I-2 20%, low quality of evidence). Subgroup analyses found no evidence for differences by WHO region, age, sex, socioeconomic status and type of stroke. Sensitivity analyses found no differences by outcome definition (exclusively non-fatal or fatal versus mixed) except for the comparison working >= 55 h/week versus 35-40 h/week for stroke incidence (p for subgroup differences: 0.05), risk of bias (high/probably high ratings in any domain versus low/probably low in all domains), effect estimate measures (risk versus hazard versus odds ratios) and comparator (exact versus approximate definition).Conclusions: We judged the existing bodies of evidence for human evidence as inadequate evidence for harmfulness for all exposure categories for stroke prevalence and mortality and for exposure to 41-48 h/week for stroke incidence. Evidence on exposure to 48-54 h/week and >= 55 h/week was judged as limited evidence for harmfulness and sufficient evidence for harmfulness for stroke incidence, respectively. Producing estimates for the burden of stroke attributable to exposures to working 48-54 and >= 55 h/week appears evidencebased, and the pooled effect estimates presented in this systematic review could be used as input data for the WHO/ILO Joint Estimates.
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| 5. |
- Descatha, Alexis, et al.
(författare)
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WHO/ILO work-related burden of disease and injury : Protocol for systematic reviews of exposure to long working hours and of the effect of exposure to long working hours on stroke
- 2018
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 119, s. 366-378
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Forskningsöversikt (refereegranskat)abstract
- Background: The World Health Organization (WHO) and the International Labour Organization (ILO) are developing a joint methodology for estimating the national and global work-related burden of disease and injury (WHO/ILO joint methodology), with contributions from a large network of experts. In this paper, we present the protocol for two systematic reviews of parameters for estimating the number of deaths and disability-adjusted life years from stroke attributable to exposure to long working hours, to inform the development of the WHO/ILO joint methodology. Objectives: We aim to systematically review studies on occupational exposure to long working hours (called Systematic Review 1 in the protocol) and systematically review and meta-analyse estimates of the effect of long working hours on stroke (called Systematic Review 2), applying the Navigation Guide systematic review methodology as an organizing framework, conducting both systematic reviews in tandem and in a harmonized way. Data sources: Separately for Systematic Reviews 1 and 2, we will search electronic academic databases for potentially relevant records from published and unpublished studies, including Medline, EMBASE, Web of Science, CISDOC and PsychINFO. We will also search electronic grey literature databases, Internet search engines and organizational websites; hand-search reference list of previous systematic reviews and included study records; and consult additional experts. Study eligibility and criteria: We will include working-age (>= 15 years) workers in the formal and informal economy in any WHO and/or ILO Member State, but exclude children (< 15 years) and unpaid domestic workers. For Systematic Review 1, we will include quantitative prevalence studies of relevant levels of occupational exposure to long working hours (i.e. 35-40, 41-48, 49-54 and >= 55 h/week) stratified by country, sex, age and industrial sector or occupation, in the years 2005-2018. For Systematic Review 2, we will include randomized controlled trials, cohort studies, case-control studies and other non-randomized intervention studies with an estimate of the relative effect of a relevant level of long working hours on the incidence of or mortality due to stroke, compared with the theoretical minimum risk exposure level (i.e. 35-40 h/week). Study appraisal and synthesis methods: At least two review authors will independently screen titles and abstracts against the eligibility criteria at a first stage and full texts of potentially eligible records at a second stage, followed by extraction of data from qualifying studies. At least two review authors will assess risk of bias and the quality of evidence, using the most suited tools currently available. For Systematic Review 2, if feasible, we will combine relative risks using meta-analysis. We will report results using the guidelines for accurate and transparent health estimates reporting (GATHER) for Systematic Review 1 and the preferred reporting items for systematic reviews and meta-analyses guidelines (PRISMA) for Systematic Review 2.
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| 6. |
- Hartkopf, Andreas D., et al.
(författare)
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Disseminated tumour cells from the bone marrow of early breast cancer patients : Results from an international pooled analysis
- 2021
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049. ; 154, s. 128-137
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Presence of disseminated tumour cells (DTCs) in the bone marrow (BM) has been described as a surrogate of residual disease in patients with early breast cancer (EBC). PADDY (Pooled Analysis of DTC Detection in Early Breast Cancer) is a large international analysis of pooled data that aimed to assess the prognostic impact of DTCs in patients with EBC. Experimental design: Individual patient data were collected from 11 centres. Patients with EBC and available follow-up data in whom BM sampling was performed at the time of primary diagnosis before receiving any anticancer treatment were eligible. DTCs were identified by antibody staining against epithelial cytokeratins. Multivariate Cox regression was used to compare the survival of DTC-positive versus DTC-negative patients. Results: In total, 10,307 patients were included. Of these, 2814 (27.3%) were DTC-positive. DTC detection was associated with higher tumour grade, larger tumour size, nodal positivity, oestrogen receptor and progesterone receptor negativity, and HER2 positivity (all p < 0.001). Multivariate analyses showed that DTC detection was an independent prognostic marker for overall survival, disease-free survival and distant disease-free survival with hazard ratios (HR) and 95% confidence intervals (CI) of 1.23 (95% CI: 1.06–1.43, p = 0.006), 1.30 (95% CI: 1.12–1.52, p < 0.001) and 1.30 (95% CI: 1.08–1.56, p = 0.006), respectively. There was no association between locoregional relapse-free survival and DTC detection (HR 1.21; 95% CI 0.68–2.16; p = 0.512). Conclusions: DTCs in the BM represent an independent prognostic marker in patients with EBC. The heterogeneous metastasis-initiating potential of DTCs is consistent with the concept of cancer dormancy.
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| 7. |
- Ninan, Neethu, et al.
(författare)
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Plasma assisted design of biocompatible 3D printed PCL/silver nanoparticle scaffolds : in vitro and in vivo analyses
- 2021
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Ingår i: Materials Advances. - : Royal Society of Chemistry (RSC). - 2633-5409. ; 2:20, s. 6620-6630
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Tidskriftsartikel (refereegranskat)abstract
- 3D printing provides numerous opportunities for designing tissue engineering constructs with intricate porosity, geometry and favourable mechanical properties and has the potential to revolutionize medical treatments. However, an often-encountered restriction is the selection of materials suitable for utilization in 3D printing, not all of which have appropriate biocompatibility properties. In this work, fused deposition modeling was employed to fabricate 3D PCL constructs without the use of any solvent. Plasma deposition was used to modify the surface of the scaffolds, followed by immobilization of silver nanoparticles. The physico-chemical and mechanical analyses demonstrated that the scaffolds retained their porosity and mechanical integrity. The mechanical properties evaluated by the nanoindentation technique demonstrated an increase in reduced modulus to 1.87 +/- 0.012 GPa for PCL scaffolds functionalized with silver nanoparticles for 24 hours. We also showed complete prevention of colonization by medically relevant pathogens. The modified scaffolds had good biocompatibility. The immune response studies in the culture of macrophages confirmed a reduction in the level of expression of pro-inflammatory cytokines which is a key requirement for successful wound healing. The in vivo studies on Sprague Dawley rats indicated enhanced angiogenesis and the absence of foreign body reaction for scaffolds functionalized with silver nanoparticles for 6 hours. The 3D printing approach presented in this study provides new sustainable opportunities that can be adopted for designing biomaterial constructs with enhanced biological properties.
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| 8. |
- Oldenhof, Martijn, et al.
(författare)
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Industry-Scale Orchestrated Federated Learning for Drug Discovery
- 2023
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Ingår i: Proceedings of the 37th AAAI Conference on Artificial Intelligence, AAAI 2023. ; 37, s. 15576-15584
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Konferensbidrag (refereegranskat)abstract
- To apply federated learning to drug discovery we developed a novel platform in the context of European Innovative Medicines Initiative (IMI) project MELLODDY (grant n°831472), which was comprised of 10 pharmaceutical companies, academic research labs, large industrial companies and startups. The MELLODDY platform was the first industry-scale platform to enable the creation of a global federated model for drug discovery without sharing the confidential data sets of the individual partners. The federated model was trained on the platform by aggregating the gradients of all contributing partners in a cryptographic, secure way following each training iteration. The platform was deployed on an Amazon Web Services (AWS) multi-account architecture running Kubernetes clusters in private subnets. Organisationally, the roles of the different partners were codified as different rights and permissions on the platform and administrated in a decentralized way. The MELLODDY platform generated new scientific discoveries which are described in a companion paper.
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| 9. |
- Quentin, Audrey G, et al.
(författare)
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Non-structural carbohydrates in woody plants compared among laboratories.
- 2015
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Ingår i: Tree physiology. - : Oxford University Press (OUP). - 1758-4469 .- 0829-318X. ; 35:11, s. 1146-1165
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Tidskriftsartikel (refereegranskat)abstract
- Non-structural carbohydrates (NSC) in plant tissue are frequently quantified to make inferences about plant responses to environmental conditions. Laboratories publishing estimates of NSC of woody plants use many different methods to evaluate NSC. We asked whether NSC estimates in the recent literature could be quantitatively compared among studies. We also asked whether any differences among laboratories were related to the extraction and quantification methods used to determine starch and sugar concentrations. These questions were addressed by sending sub-samples collected from five woody plant tissues, which varied in NSC content and chemical composition, to 29 laboratories. Each laboratory analyzed the samples with their laboratory-specific protocols, based on recent publications, to determine concentrations of soluble sugars, starch and their sum, total NSC. Laboratory estimates differed substantially for all samples. For example, estimates for Eucalyptus globulus leaves (EGL) varied from 23 to 116 (mean = 56) mg g(-1) for soluble sugars, 6-533 (mean = 94) mg g(-1) for starch and 53-649 (mean = 153) mg g(-1) for total NSC. Mixed model analysis of variance showed that much of the variability among laboratories was unrelated to the categories we used for extraction and quantification methods (method category R(2) = 0.05-0.12 for soluble sugars, 0.10-0.33 for starch and 0.01-0.09 for total NSC). For EGL, the difference between the highest and lowest least squares means for categories in the mixed model analysis was 33 mg g(-1) for total NSC, compared with the range of laboratory estimates of 596 mg g(-1). Laboratories were reasonably consistent in their ranks of estimates among tissues for starch (r = 0.41-0.91), but less so for total NSC (r = 0.45-0.84) and soluble sugars (r = 0.11-0.83). Our results show that NSC estimates for woody plant tissues cannot be compared among laboratories. The relative changes in NSC between treatments measured within a laboratory may be comparable within and between laboratories, especially for starch. To obtain comparable NSC estimates, we suggest that users can either adopt the reference method given in this publication, or report estimates for a portion of samples using the reference method, and report estimates for a standard reference material. Researchers interested in NSC estimates should work to identify and adopt standard methods.
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| 10. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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