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- Thomas, HS, et al.
(författare)
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- 2019
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swepub:Mat__t
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- Bethlehem, RAI, et al.
(författare)
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Brain charts for the human lifespan
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 604:79057906, s. 525-
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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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- 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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- Cunningham, A. L., et al.
(författare)
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Efficacy of the Herpes Zoster Subunit Vaccine in Adults 70 Years of Age or Older
- 2016
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 375:11, s. 1019-1032
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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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- Lønborg, C., et al.
(författare)
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A global database of dissolved organic matter (DOM) concentration measurements in coastal waters (CoastDOM v1)
- 2024
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Ingår i: Earth System Science Data. - : Copernicus Publications. - 1866-3508 .- 1866-3516. ; 16:2, s. 1107-1119
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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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- López-Fauqued, M., et al.
(författare)
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Safety profile of the adjuvanted recombinant zoster vaccine : Pooled analysis of two large randomised phase 3 trials
- 2019
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Ingår i: Vaccine. - : Elsevier Ltd. - 0264-410X .- 1873-2518. ; 37:18, s. 2482-2493
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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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- Stokes, B. H., et al.
(författare)
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Plasmodium falciparum K13 mutations in Africa and Asia impact artemisinin resistance and parasite fitness
- 2021
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Ingår i: eLife. - 2050-084X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- The emergence of mutant K13-mediated artemisinin (ART) resistance in Plasmodium falciparum malaria parasites has led to widespread treatment failures across Southeast Asia. In Africa, K13-propeller genotyping confirms the emergence of the R561 H mutation in Rwanda and highlights the continuing dominance of wild-type K13 elsewhere. Using gene editing, we show that R561 H, along with C580Y and M5791, confer elevated in vitro ART resistance in some African strains, contrasting with minimal changes in ART susceptibility in others. C580Y and M5791 cause substantial fitness costs, which may slow their dissemination in high-transmission settings, in contrast with R561 H that in African 3D7 parasites is fitness neutral. In Cambodia, K13 genotyping highlights the increasing spatio-temporal dominance of C580Y. Editing multiple K13 mutations into a panel of Southeast Asian strains reveals that only the R561 H variant yields ART resistance comparable to C580Y. In Asian Dd2 parasites C580Y shows no fitness cost, in contrast with most other K13 mutations tested, including R561H. Editing of point mutations in ferredoxin or mdr2, earlier associated with resistance, has no impact on ART susceptibility or parasite fitness. These data underline the complex interplay between K13 mutations, parasite survival, growth and genetic background in contributing to the spread of ART resistance.
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- Kalman, L. V., et al.
(författare)
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Pharmacogenetic allele nomenclature: International workgroup recommendations for test result reporting
- 2016
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Ingår i: Clinical Pharmacology and Therapeutics. - : WILEY-BLACKWELL. - 0009-9236 .- 1532-6535. ; 99:2, s. 172-185
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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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- Murton, Bramley J., et al.
(författare)
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Geological fate of seafloor massive sulphides at the TAG hydrothermal field (Mid-Atlantic Ridge)
- 2019
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Ingår i: Ore Geology Reviews. - : Elsevier. - 0169-1368 .- 1872-7360. ; 107, s. 903-925
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Forskningsöversikt (refereegranskat)abstract
- Deep-sea mineral deposits potentially represent vast metal resources that could make a major contribution to future global raw material supply. Increasing demand for these metals, many of which are required to enable a low-carbon and high-technology society and to relieve pressure on land-based resources, may result in deep sea mining within the next decade. Seafloor massive sulphide (SMS) deposits, containing abundant copper, zinc, gold and silver, have been the subject of recent and ongoing commercial interest. Although many seafloor hydrothermally systems have been studied, inactive SMS deposits are likely more accessible to future mining and far more abundant, but are often obscured by pelagic sediment and hence difficult tolocate. Furthermore, SMS deposits are three dimensional. Yet, to date, very few have been explored or sampled below the seafloor. Here, we describe the most comprehensive study to date of hydrothermally extinct seafloor massive sulphide (eSMS) deposits formed at a slow spreading ridge. Our approach involved two research cruises in the summer of 2016 to the Trans-Atlantic Geotraverse (TAG) hydrothermal field at 26 N on the Mid-Atlantic Ridge. These expeditions mapped a number of hydrothermally extinct SMS deposits using an autonomous underwater vehicle and remotely operated vehicle, acquired a combination of geophysical data including sub-seafloor seismic reflection and refraction data from 25 ocean bottom instruments, and recovered core using a robotic lander-type seafloor drilling rig. Together, these results that have allowed us to construct a new generic model for extinct seafloor massive sulphide deposits indicate the presence of up to five times more massive sulphide at and below the seafloor than was previously thought.
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- Raffan, Eleanor, et al.
(författare)
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A Deletion in the Canine POMC Gene Is Associated with Weight and Appetite in Obesity-Prone Labrador Retriever Dogs
- 2016
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Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131 .- 1932-7420. ; 23:5, s. 893-900
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Tidskriftsartikel (refereegranskat)abstract
- Sequencing of candidate genes for obesity in Labrador retriever dogs identified a 14 bp deletion in pro-opiomelanocortin (POMC) with an allele frequency of 12%. The deletion disrupts the b-MSH and beta-endorphin coding sequences and is associated with body weight (per allele effect of 0.33 SD), adiposity, and greater food motivation. Among other dog breeds, the deletion was only found in the closely related flat-coat retriever (FCR), where it is similarly associated with body weight and food motivation. The mutation is significantly more common in Labrador retrievers selected to become assistance dogs than pets. In conclusion, the deletion in POMC is a significant modifier of weight and appetite in Labrador retrievers and FCRs and may influence other behavioral traits.
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- Bassi, Claudio, et al.
(författare)
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The 2016 update of the International Study Group (ISGPS) definition and grading of postoperative pancreatic fistula : 11 Years After
- 2017
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Ingår i: Surgery. - : Elsevier BV. - 0039-6060 .- 1532-7361. ; 161:3, s. 584-591
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Tidskriftsartikel (refereegranskat)abstract
- Background: In 2005, the International Study Group of Pancreatic Fistula developed a definition and grading of postoperative pancreatic fistula that has been accepted universally. Eleven years later, because postoperative pancreatic fistula remains one of the most relevant and harmful complications of pancreatic operation, the International Study Group of Pancreatic Fistula classification has become the gold standard in defining postoperative pancreatic fistula in clinical practice. The aim of the present report is to verify the value of the International Study Group of Pancreatic Fistula definition and grading of postoperative pancreatic fistula and to update the International Study Group of Pancreatic Fistula classification in light of recent evidence that has emerged, as well as to address the lingering controversies about the original definition and grading of postoperative pancreatic fistula. Methods: The International Study Group of Pancreatic Fistula reconvened as the International Study Group in Pancreatic Surgery in order to perform a review of the recent literature and consequently to update and revise the grading system of postoperative pancreatic fistula. Results: Based on the literature since 2005 investigating the validity and clinical use of the original International Study Group of Pancreatic Fistula classification, a clinically relevant postoperative pancreatic fistula is now redefined as a drain output of any measurable volume of fluid with an amylase level >3 times the upper limit of institutional normal serum amylase activity, associated with a clinically relevant development/condition related directly to the postoperative pancreatic fistula. Consequently, the former "grade A postoperative pancreatic fistula" is now redefined and called a "biochemical leak," because it has no clinical importance and is no longer referred to a true pancreatic fistula. Postoperative pancreatic fistula grades B and C are confirmed but defined more strictly. In particular, grade B requires a change in the postoperative management; drains are either left in place >3 weeks or repositioned through endoscopic or percutaneous procedures. Grade C postoperative pancreatic fistula refers to those postoperative pancreatic fistula that require reoperation or lead to single or multiple organ failure and/or mortality attributable to the pancreatic fistula. Conclusion: This new definition and grading system of postoperative pancreatic fistula should lead to a more universally consistent evaluation of operative outcomes after pancreatic operation and will allow for a better comparison of techniques used to mitigate the rate and clinical impact of a pancreatic fistula. Use of this updated classification will also allow for more precise comparisons of surgical quality between surgeons and units who perform pancreatic surgery.
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- Kuemmerli, Christoph, et al.
(författare)
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Are enhanced recovery protocols after pancreatoduodenectomy still efficient when applied in elderly patients? A systematic review and individual patient data meta-analysis
- 2024
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Ingår i: Journal of Hepato-Biliary-Pancreatic Sciences. - 1868-6974. ; 31:5, s. 308-317
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Forskningsöversikt (refereegranskat)abstract
- Background: This meta-analysis investigated the effects of enhanced recovery after surgery (ERAS) protocols compared to conventional care on postoperative outcomes in patients aged 70 years or older undergoing pancreatoduodenectomy (PD). Methods: Five databases were systematically searched. Comparative studies with available individual patient data (IPD) were included. The main outcomes were postoperative morbidity, length of stay, readmission and postoperative functional recovery elements. To assess an age-dependent effect, the group was divided in septuagenarians (70–79 years) and older patients (≥80 years). Results: IPD were obtained from 15 of 31 eligible studies comprising 1109 patients. The overall complication and major complication rates were comparable in both groups (OR 0.92 [95% CI: 0.65–1.29], p =.596 and OR 1.22 [95% CI: 0.61–2.46], p =.508). Length of hospital stay tended to be shorter in the ERAS group compared to the conventional care group (−0.14 days [95% CI: −0.29 to 0.01], p =.071) while readmission rates were comparable and the total length of stay including days in hospital after readmission tended to be shorter in the ERAS group (−0.28 days [95% CI: −0.62 to 0.05], p =.069). In the subgroups, the length of stay was shorter in octogenarians treated with ERAS (−0.36 days [95% CI: −0.71 to −0.004], p =.048). The readmission rate increased slightly but not significantly while the total length of stay was not longer in the ERAS group. Conclusion: ERAS in the elderly is safe and its benefits are preserved in the care of even in patients older than 80 years. Standardized care protocol should be encouraged in all pancreatic centers.
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- Kuemmerli, Christoph, et al.
(författare)
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Impact of enhanced recovery protocols after pancreatoduodenectomy : meta-analysis
- 2022
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Ingår i: The British journal of surgery. - : Oxford University Press (OUP). - 1365-2168 .- 0007-1323. ; 109:3, s. 256-266
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: This individual-patient data meta-analysis investigated the effects of enhanced recovery after surgery (ERAS) protocols compared with conventional care on postoperative outcomes in patients undergoing pancreatoduodenectomy. METHODS: The Cochrane Library, MEDLINE, Embase, Scopus, and Web of Science were searched systematically for articles reporting outcomes of ERAS after pancreatoduodenectomy published up to August 2020. Comparative studies were included. Main outcomes were postoperative functional recovery elements, postoperative morbidity, duration of hospital stay, and readmission. RESULTS: Individual-patient data were obtained from 17 of 31 eligible studies comprising 3108 patients. Time to liquid (mean difference (MD) -3.23 (95 per cent c.i. -4.62 to -1.85) days; P < 0.001) and solid (-3.84 (-5.09 to -2.60) days; P < 0.001) intake, time to passage of first stool (MD -1.38 (-1.82 to -0.94) days; P < 0.001) and time to removal of the nasogastric tube (3.03 (-4.87 to -1.18) days; P = 0.001) were reduced with ERAS. ERAS was associated with lower overall morbidity (risk difference (RD) -0.04, 95 per cent c.i. -0.08 to -0.01; P = 0.015), less delayed gastric emptying (RD -0.11, -0.22 to -0.01; P = 0.039) and a shorter duration of hospital stay (MD -2.33 (-2.98 to -1.69) days; P < 0.001) without a higher readmission rate. CONCLUSION: ERAS improved postoperative outcome after pancreatoduodenectomy. Implementation should be encouraged.
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