| 1. |
- Manzano-Nunez, Ramiro, et al.
(författare)
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Outcomes and management approaches of resuscitative endovascular balloon occlusion of the aorta based on the income of countries
- 2020
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Ingår i: World Journal of Emergency Surgery. - : Springer Science and Business Media LLC. - 1749-7922. ; 15:57
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Tidskriftsartikel (refereegranskat)abstract
- © 2020 The Author(s). Background: Resuscitative endovascular balloon occlusion of the aorta (REBOA) could provide a survival benefit to severely injured patients as it may improve their initial ability to survive the hemorrhagic shock. Although the evidence supporting the use of REBOA is not conclusive, its use has expanded worldwide. We aim to compare the management approaches and clinical outcomes of trauma patients treated with REBOA according to the countries' income based on the World Bank Country and Lending Groups. Methods: We used data from the AORTA (USA) and the ABOTrauma (multinational) registries. Patients were stratified into two groups: (1) high-income countries (HICs) and (2) low-to-middle income countries (LMICs). Propensity score matching extracted 1:1 matched pairs of subjects who were from an LMIC or a HIC based on age, gender, the presence of pupillary response on admission, impeding hypotension (SBP ≤ 80), trauma mechanism, ISS, the necessity of CPR on arrival, the location of REBOA insertion (emergency room or operating room) and the amount of PRBCs transfused in the first 24 h. Logistic regression (LR) was used to examine the association of LMICs and mortality. Results: A total of 817 trauma patients from 14 countries were included. Blind percutaneous approach and surgical cutdown were the preferred means of femoral cannulation in HICs and LIMCs, respectively. Patients from LMICs had a significantly higher occurrence of MODS and respiratory failure. LR showed no differences in mortality for LMICs when compared to HICs; neither in the non-matched cohort (OR = 0.63; 95% CI: 0.36-1.09; p = 0.1) nor in the matched cohort (OR = 1.45; 95% CI: 0.63-3,33; p = 0.3). Conclusion: There is considerable variation in the management practices of REBOA and the outcomes associated with this intervention between HICs and LMICs. Although we found significant differences in multiorgan and respiratory failure rates, there were no differences in the risk-adjusted odds of mortality between the groups analyzed. Trauma surgeons practicing REBOA around the world should joint efforts to standardize the practice of this endovascular technology worldwide.
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| 2. |
- Brownstein, Catherine A., et al.
(författare)
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An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge
- 2014
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 15:3, s. R53-
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. Results: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. Conclusions: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups.
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| 3. |
- Falster, Daniel, et al.
(författare)
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AusTraits, a curated plant trait database for the Australian flora
- 2021
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Ingår i: Scientific Data. - : Nature Portfolio. - 2052-4463. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- We introduce the AusTraits database - a compilation of values of plant traits for taxa in the Australian flora (hereafter AusTraits). AusTraits synthesises data on 448 traits across 28,640 taxa from field campaigns, published literature, taxonomic monographs, and individual taxon descriptions. Traits vary in scope from physiological measures of performance (e.g. photosynthetic gas exchange, water-use efficiency) to morphological attributes (e.g. leaf area, seed mass, plant height) which link to aspects of ecological variation. AusTraits contains curated and harmonised individual- and species-level measurements coupled to, where available, contextual information on site properties and experimental conditions. This article provides information on version 3.0.2 of AusTraits which contains data for 997,808 trait-by-taxon combinations. We envision AusTraits as an ongoing collaborative initiative for easily archiving and sharing trait data, which also provides a template for other national or regional initiatives globally to fill persistent gaps in trait knowledge.
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| 4. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 5. |
- Abbasi, Rasha, et al.
(författare)
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IceCube search for neutrinos from GRB 221009A
- 2023
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Ingår i: Proceedings of 38th International Cosmic Ray Conference - PoS(ICRC 2023). - : Sissa Medialab. ; , s. 1511-
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Konferensbidrag (refereegranskat)abstract
- GRB 221009A is the brightest Gamma Ray Burst (GRB) ever observed. The observed extremelyhigh flux of high and very-high-energy photons provide a unique opportunity to probe the predictedneutrino counterpart to the electromagnetic emission. We have used a variety of methods to searchfor neutrinos in coincidence with the GRB over several time windows during the precursor, promptand afterglow phases of the GRB. MeV scale neutrinos are studied using photo-multiplier ratescalers which are normally used to search for galactic core-collapse supernovae neutrinos. GeVneutrinos are searched starting with DeepCore triggers. These events don’t have directionallocalization, but instead can indicate an excess in the rate of events. 10 GeV - 1 TeV and >TeVneutrinos are searched using traditional neutrino point source methods which take into accountthe direction and time of events with DeepCore and the entire IceCube detector respectively. The>TeV results include both a fast-response analysis conducted by IceCube in real-time with timewindows of T0 − 1 to T0 + 2 hours and T0 ± 1 day around the time of GRB 221009A, as well asan offline analysis with 3 new time windows up to a time window of T0 − 1 to T0 + 14 days, thelongest time period we consider. The combination of observations by IceCube covers 9 ordersof magnitude in neutrino energy, from MeV to PeV, placing upper limits across the range forpredicted neutrino emission.
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| 6. |
- 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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| 7. |
- Biswas, Dhruva, et al.
(författare)
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A clonal expression biomarker associates with lung cancer mortality
- 2019
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 25:10, s. 1540-1548
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Tidskriftsartikel (refereegranskat)abstract
- An aim of molecular biomarkers is to stratify patients with cancer into disease subtypes predictive of outcome, improving diagnostic precision beyond clinical descriptors such as tumor stage(1). Transcriptomic intratumor heterogeneity (RNA-ITH) has been shown to confound existing expression-based biomarkers across multiple cancer types(2-6). Here, we analyze multi-region whole-exome and RNA sequencing data for 156 tumor regions from 48 patients enrolled in the TRACERx study to explore and control for RNA-ITH in non-small cell lung cancer. We find that chromosomal instability is a major driver of RNA-ITH, and existing prognostic gene expression signatures are vulnerable to tumor sampling bias. To address this, we identify genes expressed homogeneously within individual tumors that encode expression modules of cancer cell proliferation and are often driven by DNA copy-number gains selected early in tumor evolution. Clonal transcriptomic biomarkers overcome tumor sampling bias, associate with survival independent of clinicopathological risk factors, and may provide a general strategy to refine biomarker design across cancer types.
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| 8. |
- Ebersole, Charles R., et al.
(författare)
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Many Labs 5: Testing Pre-Data-Collection Peer Review as an Intervention to Increase Replicability
- 2020
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Ingår i: Advances in Methods and Practices in Psychological Science. - : Sage. - 2515-2467 .- 2515-2459. ; 3:3, s. 309-331
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Tidskriftsartikel (refereegranskat)abstract
- Replication studies in psychological science sometimes fail to reproduce prior findings. If these studies use methods that are unfaithful to the original study or ineffective in eliciting the phenomenon of interest, then a failure to replicate may be a failure of the protocol rather than a challenge to the original finding. Formal pre-data-collection peer review by experts may address shortcomings and increase replicability rates. We selected 10 replication studies from the Reproducibility Project: Psychology (RP:P; Open Science Collaboration, 2015) for which the original authors had expressed concerns about the replication designs before data collection; only one of these studies had yielded a statistically significant effect (p < .05). Commenters suggested that lack of adherence to expert review and low-powered tests were the reasons that most of these RP:P studies failed to replicate the original effects. We revised the replication protocols and received formal peer review prior to conducting new replication studies. We administered the RP:P and revised protocols in multiple laboratories (median number of laboratories per original study = 6.5, range = 3-9; median total sample = 1,279.5, range = 276-3,512) for high-powered tests of each original finding with both protocols. Overall, following the preregistered analysis plan, we found that the revised protocols produced effect sizes similar to those of the RP:P protocols (Delta r = .002 or .014, depending on analytic approach). The median effect size for the revised protocols (r = .05) was similar to that of the RP:P protocols (r = .04) and the original RP:P replications (r = .11), and smaller than that of the original studies (r = .37). Analysis of the cumulative evidence across the original studies and the corresponding three replication attempts provided very precise estimates of the 10 tested effects and indicated that their effect sizes (median r = .07, range = .00-.15) were 78% smaller, on average, than the original effect sizes (median r = .37, range = .19-.50).
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| 9. |
- Fazey, Ioan, et al.
(författare)
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Transforming knowledge systems for life on Earth : Visions of future systems and how to get there
- 2020
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Ingår i: Energy Research & Social Science. - : Elsevier. - 2214-6296 .- 2214-6326. ; 70
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Tidskriftsartikel (refereegranskat)abstract
- Formalised knowledge systems, including universities and research institutes, are important for contemporary societies. They are, however, also arguably failing humanity when their impact is measured against the level of progress being made in stimulating the societal changes needed to address challenges like climate change. In this research we used a novel futures-oriented and participatory approach that asked what future envisioned knowledge systems might need to look like and how we might get there. Findings suggest that envisioned future systems will need to be much more collaborative, open, diverse, egalitarian, and able to work with values and systemic issues. They will also need to go beyond producing knowledge about our world to generating wisdom about how to act within it. To get to envisioned systems we will need to rapidly scale methodological innovations, connect innovators, and creatively accelerate learning about working with intractable challenges. We will also need to create new funding schemes, a global knowledge commons, and challenge deeply held assumptions. To genuinely be a creative force in supporting longevity of human and non-human life on our planet, the shift in knowledge systems will probably need to be at the scale of the enlightenment and speed of the scientific and technological revolution accompanying the second World War. This will require bold and strategic action from governments, scientists, civic society and sustained transformational intent.
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| 10. |
- Haggarty, Connor James, et al.
(författare)
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Vicarious ratings of social touch the effect of age and autistic traits
- 2021
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Ingår i: Scientific Reports. - : Nature Portfolio. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Tactile sensitivities are common in Autism Spectrum Conditions (autism). Psychophysically, slow, gentle stroking touch is typically rated as more pleasant than faster or slower touch. Vicarious ratings of social touch results in a similar pattern of velocity dependent hedonic ratings as directly felt touch. Here we investigated whether adults and childrens vicarious ratings vary according to autism diagnosis and self-reported autistic traits. Adults scoring high on the AQ rated stroking touch on the palm as less pleasant than a Low AQ group. However, in contrast to our hypothesis, we did not find any effect of autism diagnosis on childrens touch ratings despite parental reports highlighting significant somatosensory sensitivities. These results are discussed in terms of underpinning sensory and cognitive factors.
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| 11. |
- Hamilton, Douglas S., et al.
(författare)
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Impact of Changes to the Atmospheric Soluble Iron Deposition Flux on Ocean Biogeochemical Cycles in the Anthropocene
- 2020
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Ingår i: Global Biogeochemical Cycles. - 0886-6236. ; 34:3
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Tidskriftsartikel (refereegranskat)abstract
- Iron can be a growth‐limiting nutrient for phytoplankton, modifying rates of net primary production, nitrogen fixation, and carbon export ‐ highlighting the importance of new iron inputs from the atmosphere. The bioavailable iron fraction depends on the emission source and the dissolution during transport. The impacts of anthropogenic combustion and land use change on emissions from industrial, domestic, shipping, desert, and wildfire sources suggest that Northern Hemisphere soluble iron deposition has likely been enhanced between 2% and 68% over the Industrial Era. If policy and climate follow the intermediate Representative Concentration Pathway 4.5 trajectory, then results suggest that Southern Ocean (>30°S) soluble iron deposition would be enhanced between 63% and 95% by 2100. Marine net primary productivity and carbon export within the open ocean are most sensitive to changes in soluble iron deposition in the Southern Hemisphere; this is predominantly driven by fire rather than dust iron sources. Changes in iron deposition cause large perturbations to the marine nitrogen cycle, up to 70% increase in denitrification and 15% increase in nitrogen fixation, but only modestly impacts the carbon cycle and atmospheric CO2 concentrations (1–3 ppm). Regionally, primary productivity increases due to increased iron deposition are often compensated by offsetting decreases downstream corresponding to equivalent changes in the rate of phytoplankton macronutrient uptake, particularly in the equatorial Pacific. These effects are weaker in the Southern Ocean, suggesting that changes in iron deposition in this region dominates the global carbon cycle and climate response.
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| 12. |
- Janko, Matthew, et al.
(författare)
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Contemporary Outcomes After Partial Resection of Infected Aortic Grafts
- 2021
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Ingår i: Annals of Vascular Surgery. - : Elsevier. - 0890-5096 .- 1615-5947. ; 76, s. 202-210
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Aortic graft infection remains a considerable clinical challenge, and it is unclear which variables are associated with adverse outcomes among patients undergoing partial resection.METHODS: A retrospective, multi-institutional study of patients who underwent partial resection of infected aortic grafts from 2002 to 2014 was performed using a standard database. Baseline demographics, comorbidities, operative, and postoperative variables were recorded. The primary outcome was mortality. Descriptive statistics, Kaplan-Meier (KM) survival analysis, and Cox regression analysis were performed.RESULTS: One hundred fourteen patients at 22 medical centers in 6 countries underwent partial resection of an infected aortic graft. Seventy percent were men with median age 70 years. Ninety-seven percent had a history of open aortic bypass graft: 88 (77%) patients had infected aortobifemoral bypass, 18 (16%) had infected aortobiiliac bypass, and 1 (0.8%) had an infected thoracic graft. Infection was diagnosed at a median 4.3 years post-implant. All patients underwent partial resection followed by either extra-anatomic (47%) or in situ (53%) vascular reconstruction. Median follow-up period was 17 months (IQR 1, 50 months). Thirty-day mortality was 17.5%. The KM-estimated median survival from time of partial resection was 3.6 years. There was no significant survival difference between those undergoing in situ reconstruction or extra-anatomic bypass (P = 0.6). During follow up, 72% of repairs remained patent and 11% of patients underwent major amputation. On univariate Cox regression analysis, Candida infection was associated with increased risk of mortality (HR 2.4; P = 0.01) as well as aortoenteric fistula (HR 1.9, P = 0.03). Resection of a single graft limb only to resection of abdominal (graft main body) infection was associated with decreased risk of mortality (HR 0.57, P = 0.04), as well as those with American Society of Anesthesiologists classification less than 3 (HR 0.35, P = 0.04). Multivariate analysis did not reveal any factors significantly associated with mortality. Persistent early infection was noted in 26% of patients within 30 days postoperatively, and 39% of patients were found to have any post-repair infection during the follow-up period. Two patients (1.8%) were found to have a late reinfection without early persistent postoperative infection. Patients with any post-repair infection were older (67 vs. 60 years, P = 0.01) and less likely to have patent repairs during follow up (59% vs. 32%, P = 0.01). Patients with aortoenteric fistula had a higher rate of any post-repair infection (63% vs. 29%, P < 0.01)CONCLUSION: This large multi-center study suggests that patients who have undergone partial resection of infected aortic grafts may be at high risk of death or post-repair infection, especially older patients with abdominal infection not isolated to a single graft limb, or with Candida infection or aortoenteric fistula. Late reinfection correlated strongly with early persistent postoperative infection, raising concern for occult retained infected graft material.
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| 13. |
- Kitahara, Cari M., et al.
(författare)
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Association between Class III Obesity (BMI of 40-59 kg/m(2)) and Mortality : A Pooled Analysis of 20 Prospective Studies
- 2014
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Ingår i: PLoS Medicine. - : PUBLIC LIBRARY SCIENCE. - 1549-1277 .- 1549-1676. ; 11:7
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Tidskriftsartikel (refereegranskat)abstract
- Background: The prevalence of class III obesity (body mass index [BMI]>= 40 kg/m(2)) has increased dramatically in several countries and currently affects 6% of adults in the US, with uncertain impact on the risks of illness and death. Using data from a large pooled study, we evaluated the risk of death, overall and due to a wide range of causes, and years of life expectancy lost associated with class III obesity. Methods and Findings: In a pooled analysis of 20 prospective studies from the United States, Sweden, and Australia, we estimated sex-and age-adjusted total and cause-specific mortality rates (deaths per 100,000 persons per year) and multivariable-adjusted hazard ratios for adults, aged 19-83 y at baseline, classified as obese class III (BMI 40.0-59.9 kg/m(2)) compared with those classified as normal weight (BMI 18.5-24.9 kg/m(2)). Participants reporting ever smoking cigarettes or a history of chronic disease (heart disease, cancer, stroke, or emphysema) on baseline questionnaires were excluded. Among 9,564 class III obesity participants, mortality rates were 856.0 in men and 663.0 in women during the study period (19762009). Among 304,011 normal-weight participants, rates were 346.7 and 280.5 in men and women, respectively. Deaths from heart disease contributed largely to the excess rates in the class III obesity group (rate differences = 238.9 and 132.8 in men and women, respectively), followed by deaths from cancer (rate differences = 36.7 and 62.3 in men and women, respectively) and diabetes (rate differences = 51.2 and 29.2 in men and women, respectively). Within the class III obesity range, multivariable-adjusted hazard ratios for total deaths and deaths due to heart disease, cancer, diabetes, nephritis/nephrotic syndrome/nephrosis, chronic lower respiratory disease, and influenza/pneumonia increased with increasing BMI. Compared with normal-weight BMI, a BMI of 40-44.9, 45-49.9, 50-54.9, and 55-59.9 kg/m(2) was associated with an estimated 6.5 (95% CI: 5.7-7.3), 8.9 (95% CI: 7.4-10.4), 9.8 (95% CI: 7.4-12.2), and 13.7 (95% CI: 10.5-16.9) y of life lost. A limitation was that BMI was mainly ascertained by self-report. Conclusions: Class III obesity is associated with substantially elevated rates of total mortality, with most of the excess deaths due to heart disease, cancer, and diabetes, and major reductions in life expectancy compared with normal weight.
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| 14. |
- Li, You, et al.
(författare)
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Global patterns in monthly activity of influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus : a systematic analysis
- 2019
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Ingår i: The Lancet Global Health. - : Elsevier. - 2214-109X. ; 7:8, s. e1031-e1045
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus are the most common viruses associated with acute lower respiratory infections in young children (<5 years) and older people (≥65 years). A global report of the monthly activity of these viruses is needed to inform public health strategies and programmes for their control.METHODS: In this systematic analysis, we compiled data from a systematic literature review of studies published between Jan 1, 2000, and Dec 31, 2017; online datasets; and unpublished research data. Studies were eligible for inclusion if they reported laboratory-confirmed incidence data of human infection of influenza virus, respiratory syncytial virus, parainfluenza virus, or metapneumovirus, or a combination of these, for at least 12 consecutive months (or 52 weeks equivalent); stable testing practice throughout all years reported; virus results among residents in well-defined geographical locations; and aggregated virus results at least on a monthly basis. Data were extracted through a three-stage process, from which we calculated monthly annual average percentage (AAP) as the relative strength of virus activity. We defined duration of epidemics as the minimum number of months to account for 75% of annual positive samples, with each component month defined as an epidemic month. Furthermore, we modelled monthly AAP of influenza virus and respiratory syncytial virus using site-specific temperature and relative humidity for the prediction of local average epidemic months. We also predicted global epidemic months of influenza virus and respiratory syncytial virus on a 5° by 5° grid. The systematic review in this study is registered with PROSPERO, number CRD42018091628.FINDINGS: We initally identified 37 335 eligible studies. Of 21 065 studies remaining after exclusion of duplicates, 1081 full-text articles were assessed for eligibility, of which 185 were identified as eligible. We included 246 sites for influenza virus, 183 sites for respiratory syncytial virus, 83 sites for parainfluenza virus, and 65 sites for metapneumovirus. Influenza virus had clear seasonal epidemics in winter months in most temperate sites but timing of epidemics was more variable and less seasonal with decreasing distance from the equator. Unlike influenza virus, respiratory syncytial virus had clear seasonal epidemics in both temperate and tropical regions, starting in late summer months in the tropics of each hemisphere, reaching most temperate sites in winter months. In most temperate sites, influenza virus epidemics occurred later than respiratory syncytial virus (by 0·3 months [95% CI -0·3 to 0·9]) while no clear temporal order was observed in the tropics. Parainfluenza virus epidemics were found mostly in spring and early summer months in each hemisphere. Metapneumovirus epidemics occurred in late winter and spring in most temperate sites but the timing of epidemics was more diverse in the tropics. Influenza virus epidemics had shorter duration (3·8 months [3·6 to 4·0]) in temperate sites and longer duration (5·2 months [4·9 to 5·5]) in the tropics. Duration of epidemics was similar across all sites for respiratory syncytial virus (4·6 months [4·3 to 4·8]), as it was for metapneumovirus (4·8 months [4·4 to 5·1]). By comparison, parainfluenza virus had longer duration of epidemics (6·3 months [6·0 to 6·7]). Our model had good predictability in the average epidemic months of influenza virus in temperate regions and respiratory syncytial virus in both temperate and tropical regions. Through leave-one-out cross validation, the overall prediction error in the onset of epidemics was within 1 month (influenza virus -0·2 months [-0·6 to 0·1]; respiratory syncytial virus 0·1 months [-0·2 to 0·4]).INTERPRETATION: This study is the first to provide global representations of month-by-month activity of influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus. Our model is helpful in predicting the local onset month of influenza virus and respiratory syncytial virus epidemics. The seasonality information has important implications for health services planning, the timing of respiratory syncytial virus passive prophylaxis, and the strategy of influenza virus and future respiratory syncytial virus vaccination.FUNDING: European Union Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe (RESCEU).
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| 15. |
- Margulies, Elliott H, et al.
(författare)
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Analyses of deep mammalian sequence alignments and constraint predictions for 1% of the human genome
- 2007
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 17:6, s. 760-774
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Tidskriftsartikel (refereegranskat)abstract
- A key component of the ongoing ENCODE project involves rigorous comparative sequence analyses for the initially targeted 1% of the human genome. Here, we present orthologous sequence generation, alignment, and evolutionary constraint analyses of 23 mammalian species for all ENCODE targets. Alignments were generated using four different methods; comparisons of these methods reveal large-scale consistency but substantial differences in terms of small genomic rearrangements, sensitivity (sequence coverage), and specificity (alignment accuracy). We describe the quantitative and qualitative trade-offs concomitant with alignment method choice and the levels of technical error that need to be accounted for in applications that require multisequence alignments. Using the generated alignments, we identified constrained regions using three different methods. While the different constraint-detecting methods are in general agreement, there are important discrepancies relating to both the underlying alignments and the specific algorithms. However, by integrating the results across the alignments and constraint-detecting methods, we produced constraint annotations that were found to be robust based on multiple independent measures. Analyses of these annotations illustrate that most classes of experimentally annotated functional elements are enriched for constrained sequences; however, large portions of each class (with the exception of protein-coding sequences) do not overlap constrained regions. The latter elements might not be under primary sequence constraint, might not be constrained across all mammals, or might have expendable molecular functions. Conversely, 40% of the constrained sequences do not overlap any of the functional elements that have been experimentally identified. Together, these findings demonstrate and quantify how many genomic functional elements await basic molecular characterization.
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| 16. |
- Moore, Derek G., et al.
(författare)
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Infants perceive human point-light displays as solid forms
- 2007
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Ingår i: Cognition. - : Elsevier BV. - 0010-0277 .- 1873-7838. ; 104, s. 377-396
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Tidskriftsartikel (refereegranskat)abstract
- While five-month-old infants show orientation-specific sensitivity to changes in the motion and occlusion patterns of human point-light displays, it is not known whether infants are capable of binding a human representation to these displays. Furthermore, it has been suggested that infants do not encode the same physical properties for humans and material objects. To explore these issues we tested whether infants would selectively apply the principle of solidity to upright human displays. In the first experiment infants aged six and nine months were repeatedly shown a human point-light display walking across a computer screen up to 10 times or until habituated. Next, they were repeatedly shown the walking display passing behind an in-depth representation of a table, and finally they were shown the human display appearing to pass through the table top in violation of the solidity of the hidden human form. Both six- and nine-month-old infants showed significantly greater recovery of attention to this final phase. This suggests that infants are able to bind a solid vertical form to human motion. In two further control experiments we presented displays that contained similar patterns of motion but were not perceived by adults as human. Six- and nine-month-old infants did not show recovery of attention when a scrambled display or an inverted human display passed through the table. Thus, the binding of a solid human form to a display in only seems to occur for upright human motion. The paper considers the implications of these findings in relation to theories of infants’ developing conceptions of objects, humans and animals. ?? 2006 Elsevier B.V. All rights reserved.
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| 17. |
- Moore, Keith J M, et al.
(författare)
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Loop-Mediated Isothermal Amplification Detection of SARS-CoV-2 and Myriad Other Applications
- 2021
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Ingår i: Journal of Biomolecular Techniques. - : Association of Biomolecular Resource Facilities. - 1524-0215 .- 1943-4731. ; 32:3, s. 228-275
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Forskningsöversikt (refereegranskat)abstract
- As the second year of the COVID-19 pandemic begins, it remains clear that a massive increase in the ability to test for SARS-CoV-2 infections in a myriad of settings is critical to controlling the pandemic and to preparing for future outbreaks. The current gold standard for molecular diagnostics is the polymerase chain reaction (PCR), but the extraordinary and unmet demand for testing in a variety of environments means that both complementary and supplementary testing solutions are still needed. This review highlights the role that loop-mediated isothermal amplification (LAMP) has had in filling this global testing need, providing a faster and easier means of testing, and what it can do for future applications, pathogens, and the preparation for future outbreaks. This review describes the current state of the art for research of LAMP-based SARS-CoV-2 testing, as well as its implications for other pathogens and testing. The authors represent the global LAMP (gLAMP) Consortium, an international research collective, which has regularly met to share their experiences on LAMP deployment and best practices; sections are devoted to all aspects of LAMP testing, including preanalytic sample processing, target amplification, and amplicon detection, then the hardware and software required for deployment are discussed, and finally, a summary of the current regulatory landscape is provided. Included as well are a series of first-person accounts of LAMP method development and deployment. The final discussion section provides the reader with a distillation of the most validated testing methods and their paths to implementation. This review also aims to provide practical information and insight for a range of audiences: for a research audience, to help accelerate research through sharing of best practices; for an implementation audience, to help get testing up and running quickly; and for a public health, clinical, and policy audience, to help convey the breadth of the effect that LAMP methods have to offer.
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| 18. |
- Moore, Tadhg N, et al.
(författare)
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LakeEnsemblR : An R package that facilitates ensemble modelling of lakes
- 2021
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Ingår i: Environmental Modelling & Software. - : Elsevier. - 1364-8152 .- 1873-6726. ; 143
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Tidskriftsartikel (refereegranskat)abstract
- Model ensembles have several benefits compared to single-model applications but are not frequently used within the lake modelling community. Setting up and running multiple lake models can be challenging and time consuming, despite the many similarities between the existing models (forcing data, hypsograph, etc.). Here we present an R package, LakeEnsemblR, that facilitates running ensembles of five different vertical one-dimensional hydrodynamic lake models (FLake, GLM, GOTM, Simstrat, MyLake). The package requires input in a standardised format and a single configuration file. LakeEnsemblR formats these files to the input required by each model, and provides functions to run and calibrate the models. The outputs of the different models are compiled into a single file, and several post-processing operations are supported. LakeEnsemblR's workflow standardisation can simplify model benchmarking and uncertainty quantification, and improve collaborations between scientists. We showcase the successful application of LakeEnsemblR for two different lakes.
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| 19. |
- Muheim, Rachel, et al.
(författare)
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Calibration of magnetic and celestial compass cues in migratory birds - a review of cue-conflict experiments
- 2006
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Ingår i: Journal of Experimental Biology. - : The Company of Biologists. - 1477-9145 .- 0022-0949. ; 209:1, s. 2-17
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Forskningsöversikt (övrigt vetenskapligt/konstnärligt)abstract
- Migratory birds use multiple sources of compass information for orientation, including the geomagnetic field, the sun, skylight polarization patterns and star patterns. In this paper we review the results of cue-conflict experiments designed to determine the relative importance of the different compass mechanisms, and how directional information from these compass mechanisms is integrated. We focus on cue-conflict experiments in which the magnetic field was shifted in alignment relative to natural celestial cues. Consistent with the conclusions of earlier authors, our analyses suggest that during the premigratory season, celestial information is given the greatest salience and used to recalibrate the magnetic compass by both juvenile and adult birds. Sunset polarized light patterns from the region of the sky near the horizon appear to provide the calibration reference for the magnetic compass. In contrast, during migration, a majority of experiments suggest that birds rely on the magnetic field as the primary source of compass information and use it to calibrate celestial compass cues, i.e. the relative saliency of magnetic and celestial cues is reversed. An alternative possibility, however, is suggested by several experiments in which birds exposed to a cue conflict during migration appear to have recalibrated the magnetic compass, i.e. their response is similar to that of birds exposed to cue conflicts during the premigratory season. The general pattern to emerge from these analyses is that birds exposed to the cue conflict with a view of the entire sunset sky tended to recalibrate the magnetic compass, regardless of whether the cue conflict occurred during the premigratory or migratory period. In contrast, birds exposed to the cue conflict in orientation funnels and registration cages that restricted their view of the region of sky near the horizon (as was generally the case in experiments carried out during the migratory season) did not recalibrate the magnetic compass but, instead, used the magnetic compass to calibrate the other celestial compass systems. If access to critical celestial cues, rather than the timing of exposure to the cue conflict (i.e. premigratory vs migratory), determines whether recalibration of the magnetic compass occurs, this suggests that under natural conditions there may be a single calibration reference for all of the compass systems of migratory birds that is derived from sunset (and possibly also sunrise) polarized light cues from the region of sky near the horizon. In cue-conflict experiments carried out during the migratory season, there was also an interesting asymmetry in the birds' response to magnetic fields shifted clockwise and counterclockwise relative to celestial cues. We discuss two possible explanations for these differences: (1) lateral asymmetry in the role of the right and left eye in mediating light-dependent magnetic compass orientation and (2) interference from the spectral and intensity distribution of skylight at sunset with the response of the light-dependent magnetic compass.
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| 20. |
- Ochoa-Hueso, Raúl, et al.
(författare)
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Microbial processing of plant remains is co-limited by multiple nutrients in global grasslands
- 2020
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Ingår i: Global Change Biology. - : John Wiley & Sons. - 1354-1013 .- 1365-2486. ; 26:8, s. 4572-4582
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Tidskriftsartikel (refereegranskat)abstract
- Microbial processing of aggregate-unprotected organic matter inputs is key for soil fertility, long-term ecosystem carbon and nutrient sequestration and sustainable agriculture. We investigated the effects of adding multiple nutrients (nitrogen, phosphorus and potassium plus nine essential macro- and micro-nutrients) on decomposition and biochemical transformation of standard plant materials buried in 21 grasslands from four continents. Addition of multiple nutrients weakly but consistently increased decomposition and biochemical transformation of plant remains during the peak-season, concurrent with changes in microbial exoenzymatic activity. Higher mean annual precipitation and lower mean annual temperature were the main climatic drivers of higher decomposition rates, while biochemical transformation of plant remains was negatively related to temperature of the wettest quarter. Nutrients enhanced decomposition most at cool, high rainfall sites, indicating that in a warmer and drier future fertilized grassland soils will have an even more limited potential for microbial processing of plant remains.
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| 21. |
- Pace, Rishika A., et al.
(författare)
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Collagen VI glycine mutations: Perturbed assembly and a spectrum of clinical severity
- 2008
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Ingår i: Annals of Neurology. - : Wiley. - 1531-8249 .- 0364-5134. ; 64:3, s. 294-303
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The collagen VI muscular dystrophies, Bethlem myopathy and Ullrich congenital muscular dystrophy, form a continuum of clinical phenotypes. Glycine mutations in the triple helix have been identified in both Bethlem and Ullrich congenital muscular dystrophy, but it is not known why they cause these different phenotypes. Methods: We studied eight new patients who presented with a spectrum of clinical severity, screened the three collagen VI messenger RNA for mutations, and examined collagen VI biosynthesis and the assembly pathway. Results: All eight patients had heterozygous glycine mutations toward the N-terminal end of the triple helix. The mutations produced two assembly phenotypes. In the first patient group, collagen VI dimers accumulated in the cell but not the medium, microfibril formation in the medium was moderately reduced, and the amount of collagen VI in the extracellular matrix was not significantly altered. The second group had more severe assembly defects: some secreted collagen VI tetramers were not disulfide bonded, microfibril formation in the medium was severely compromised, and collagen VI in the extracellular matrix was reduced. Interpretation: These data indicate that collagen VI glycine mutations impair the assembly pathway in different ways and disease severity correlates with the assembly abnormality. In mildly affected patients, normal amounts of collagen VI were deposited in the fibroblast matrix, whereas in patients with moderate-to-severe disability, assembly defects led to a reduced collagen VI fibroblast matrix. This study thus provides an explanation for how different glycine mutations produce a spectrum of clinical severity.
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| 22. |
- Patterson, Nick, et al.
(författare)
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Large-scale migration into Britain during the Middle to Late Bronze Age
- 2022
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; , s. 588-594
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Tidskriftsartikel (refereegranskat)abstract
- Present-day people from England and Wales harbour more ancestry derived from Early European Farmers (EEF) than people of the Early Bronze Age1. To understand this, we generated genome-wide data from 793 individuals, increasing data from the Middle to Late Bronze and Iron Age in Britain by 12-fold, and Western and Central Europe by 3.5-fold. Between 1000 and 875 BC, EEF ancestry increased in southern Britain (England and Wales) but not northern Britain (Scotland) due to incorporation of migrants who arrived at this time and over previous centuries, and who were genetically most similar to ancient individuals from France. These migrants contributed about half the ancestry of Iron Age people of England and Wales, thereby creating a plausible vector for the spread of early Celtic languages into Britain. These patterns are part of a broader trend of EEF ancestry becoming more similar across central and western Europe in the Middle to Late Bronze Age, coincident with archaeological evidence of intensified cultural exchange2-6. There was comparatively less gene flow from continental Europe during the Iron Age, and Britain's independent genetic trajectory is also reflected in the rise of the allele conferring lactase persistence to ~50% by this time compared to ~7% in central Europe where it rose rapidly in frequency only a millennium later. This suggests that dairy products were used in qualitatively different ways in Britain and in central Europe over this period.
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| 23. |
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| 24. |
- Sampson, Joshua N., et al.
(författare)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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| 25. |
- Weinstein, John N., et al.
(författare)
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The cancer genome atlas pan-cancer analysis project
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:10, s. 1113-1120
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Forskningsöversikt (refereegranskat)abstract
- The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
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