| 1. |
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| 2. |
- Thomas, HS, et al.
(författare)
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- 2019
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swepub:Mat__t
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| 5. |
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| 6. |
- Drake, TM, et al.
(författare)
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Surgical site infection after gastrointestinal surgery in children: an international, multicentre, prospective cohort study
- 2020
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Ingår i: BMJ global health. - : BMJ. - 2059-7908. ; 5:12
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Tidskriftsartikel (refereegranskat)abstract
- Surgical site infection (SSI) is one of the most common healthcare-associated infections (HAIs). However, there is a lack of data available about SSI in children worldwide, especially from low-income and middle-income countries. This study aimed to estimate the incidence of SSI in children and associations between SSI and morbidity across human development settings.MethodsA multicentre, international, prospective, validated cohort study of children aged under 16 years undergoing clean-contaminated, contaminated or dirty gastrointestinal surgery. Any hospital in the world providing paediatric surgery was eligible to contribute data between January and July 2016. The primary outcome was the incidence of SSI by 30 days. Relationships between explanatory variables and SSI were examined using multilevel logistic regression. Countries were stratified into high development, middle development and low development groups using the United Nations Human Development Index (HDI).ResultsOf 1159 children across 181 hospitals in 51 countries, 523 (45·1%) children were from high HDI, 397 (34·2%) from middle HDI and 239 (20·6%) from low HDI countries. The 30-day SSI rate was 6.3% (33/523) in high HDI, 12·8% (51/397) in middle HDI and 24·7% (59/239) in low HDI countries. SSI was associated with higher incidence of 30-day mortality, intervention, organ-space infection and other HAIs, with the highest rates seen in low HDI countries. Median length of stay in patients who had an SSI was longer (7.0 days), compared with 3.0 days in patients who did not have an SSI. Use of laparoscopy was associated with significantly lower SSI rates, even after accounting for HDI.ConclusionThe odds of SSI in children is nearly four times greater in low HDI compared with high HDI countries. Policies to reduce SSI should be prioritised as part of the wider global agenda.
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| 7. |
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- 2017
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Ingår i: Physical Review D. - 2470-0010 .- 2470-0029. ; 96:2
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Tidskriftsartikel (refereegranskat)
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| 8. |
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| 9. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 10. |
- Wang, Haidong, et al.
(författare)
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Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015 : a systematic analysis for the Global Burden of Disease Study 2015
- 2016
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10053, s. 1459-1544
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures.METHODS: We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refinements to the estimation of child and adult mortality and corresponding uncertainty, parameter selection for under-5 mortality synthesis by spatiotemporal Gaussian process regression, and sibling history data processing. We also expanded the database of vital registration, survey, and census data to 14 294 geography-year datapoints. For GBD 2015, eight causes, including Ebola virus disease, were added to the previous GBD cause list for mortality. We used six modelling approaches to assess cause-specific mortality, with the Cause of Death Ensemble Model (CODEm) generating estimates for most causes. We used a series of novel analyses to systematically quantify the drivers of trends in mortality across geographies. First, we assessed observed and expected levels and trends of cause-specific mortality as they relate to the Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Second, we examined factors affecting total mortality patterns through a series of counterfactual scenarios, testing the magnitude by which population growth, population age structures, and epidemiological changes contributed to shifts in mortality. Finally, we attributed changes in life expectancy to changes in cause of death. We documented each step of the GBD 2015 estimation processes, as well as data sources, in accordance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER).FINDINGS: Globally, life expectancy from birth increased from 61·7 years (95% uncertainty interval 61·4-61·9) in 1980 to 71·8 years (71·5-72·2) in 2015. Several countries in sub-Saharan Africa had very large gains in life expectancy from 2005 to 2015, rebounding from an era of exceedingly high loss of life due to HIV/AIDS. At the same time, many geographies saw life expectancy stagnate or decline, particularly for men and in countries with rising mortality from war or interpersonal violence. From 2005 to 2015, male life expectancy in Syria dropped by 11·3 years (3·7-17·4), to 62·6 years (56·5-70·2). Total deaths increased by 4·1% (2·6-5·6) from 2005 to 2015, rising to 55·8 million (54·9 million to 56·6 million) in 2015, but age-standardised death rates fell by 17·0% (15·8-18·1) during this time, underscoring changes in population growth and shifts in global age structures. The result was similar for non-communicable diseases (NCDs), with total deaths from these causes increasing by 14·1% (12·6-16·0) to 39·8 million (39·2 million to 40·5 million) in 2015, whereas age-standardised rates decreased by 13·1% (11·9-14·3). Globally, this mortality pattern emerged for several NCDs, including several types of cancer, ischaemic heart disease, cirrhosis, and Alzheimer's disease and other dementias. By contrast, both total deaths and age-standardised death rates due to communicable, maternal, neonatal, and nutritional conditions significantly declined from 2005 to 2015, gains largely attributable to decreases in mortality rates due to HIV/AIDS (42·1%, 39·1-44·6), malaria (43·1%, 34·7-51·8), neonatal preterm birth complications (29·8%, 24·8-34·9), and maternal disorders (29·1%, 19·3-37·1). Progress was slower for several causes, such as lower respiratory infections and nutritional deficiencies, whereas deaths increased for others, including dengue and drug use disorders. Age-standardised death rates due to injuries significantly declined from 2005 to 2015, yet interpersonal violence and war claimed increasingly more lives in some regions, particularly in the Middle East. In 2015, rotaviral enteritis (rotavirus) was the leading cause of under-5 deaths due to diarrhoea (146 000 deaths, 118 000-183 000) and pneumococcal pneumonia was the leading cause of under-5 deaths due to lower respiratory infections (393 000 deaths, 228 000-532 000), although pathogen-specific mortality varied by region. Globally, the effects of population growth, ageing, and changes in age-standardised death rates substantially differed by cause. Our analyses on the expected associations between cause-specific mortality and SDI show the regular shifts in cause of death composition and population age structure with rising SDI. Country patterns of premature mortality (measured as years of life lost [YLLs]) and how they differ from the level expected on the basis of SDI alone revealed distinct but highly heterogeneous patterns by region and country or territory. Ischaemic heart disease, stroke, and diabetes were among the leading causes of YLLs in most regions, but in many cases, intraregional results sharply diverged for ratios of observed and expected YLLs based on SDI. Communicable, maternal, neonatal, and nutritional diseases caused the most YLLs throughout sub-Saharan Africa, with observed YLLs far exceeding expected YLLs for countries in which malaria or HIV/AIDS remained the leading causes of early death.INTERPRETATION: At the global scale, age-specific mortality has steadily improved over the past 35 years; this pattern of general progress continued in the past decade. Progress has been faster in most countries than expected on the basis of development measured by the SDI. Against this background of progress, some countries have seen falls in life expectancy, and age-standardised death rates for some causes are increasing. Despite progress in reducing age-standardised death rates, population growth and ageing mean that the number of deaths from most non-communicable causes are increasing in most countries, putting increased demands on health systems.
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| 19. |
- Birney, Ewan, et al.
(författare)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Tidskriftsartikel (refereegranskat)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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| 20. |
- Clark, Andrew G., et al.
(författare)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Tidskriftsartikel (refereegranskat)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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| 21. |
- Wang, Haidong, et al.
(författare)
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Estimates of global, regional, and national incidence, prevalence, and mortality of HIV, 1980-2015 : the Global Burden of Disease Study 2015.
- 2016
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Ingår i: The lancet. HIV. - : Elsevier. - 2352-3018. ; 3:8, s. e361-e387
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Timely assessment of the burden of HIV/AIDS is essential for policy setting and programme evaluation. In this report from the Global Burden of Disease Study 2015 (GBD 2015), we provide national estimates of levels and trends of HIV/AIDS incidence, prevalence, coverage of antiretroviral therapy (ART), and mortality for 195 countries and territories from 1980 to 2015.METHODS: For countries without high-quality vital registration data, we estimated prevalence and incidence with data from antenatal care clinics and population-based seroprevalence surveys, and with assumptions by age and sex on initial CD4 distribution at infection, CD4 progression rates (probability of progression from higher to lower CD4 cell-count category), on and off antiretroviral therapy (ART) mortality, and mortality from all other causes. Our estimation strategy links the GBD 2015 assessment of all-cause mortality and estimation of incidence and prevalence so that for each draw from the uncertainty distribution all assumptions used in each step are internally consistent. We estimated incidence, prevalence, and death with GBD versions of the Estimation and Projection Package (EPP) and Spectrum software originally developed by the Joint United Nations Programme on HIV/AIDS (UNAIDS). We used an open-source version of EPP and recoded Spectrum for speed, and used updated assumptions from systematic reviews of the literature and GBD demographic data. For countries with high-quality vital registration data, we developed the cohort incidence bias adjustment model to estimate HIV incidence and prevalence largely from the number of deaths caused by HIV recorded in cause-of-death statistics. We corrected these statistics for garbage coding and HIV misclassification.FINDINGS: Global HIV incidence reached its peak in 1997, at 3·3 million new infections (95% uncertainty interval [UI] 3·1-3·4 million). Annual incidence has stayed relatively constant at about 2·6 million per year (range 2·5-2·8 million) since 2005, after a period of fast decline between 1997 and 2005. The number of people living with HIV/AIDS has been steadily increasing and reached 38·8 million (95% UI 37·6-40·4 million) in 2015. At the same time, HIV/AIDS mortality has been declining at a steady pace, from a peak of 1·8 million deaths (95% UI 1·7-1·9 million) in 2005, to 1·2 million deaths (1·1-1·3 million) in 2015. We recorded substantial heterogeneity in the levels and trends of HIV/AIDS across countries. Although many countries have experienced decreases in HIV/AIDS mortality and in annual new infections, other countries have had slowdowns or increases in rates of change in annual new infections.INTERPRETATION: Scale-up of ART and prevention of mother-to-child transmission has been one of the great successes of global health in the past two decades. However, in the past decade, progress in reducing new infections has been slow, development assistance for health devoted to HIV has stagnated, and resources for health in low-income countries have grown slowly. Achievement of the new ambitious goals for HIV enshrined in Sustainable Development Goal 3 and the 90-90-90 UNAIDS targets will be challenging, and will need continued efforts from governments and international agencies in the next 15 years to end AIDS by 2030.
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| 22. |
- Menkveld, Albert J., et al.
(författare)
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Nonstandard Errors
- 2024
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Ingår i: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390
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Tidskriftsartikel (refereegranskat)abstract
- In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
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| 23. |
- Perez-Nadales, Elena, et al.
(författare)
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Predictors of mortality in solid organ transplant recipients with bloodstream infections due to carbapenemase-producing Enterobacterales : The impact of cytomegalovirus disease and lymphopenia
- 2020
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Ingår i: American Journal of Transplantation. - : WILEY. - 1600-6135 .- 1600-6143. ; 20:6, s. 1629-1641
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Tidskriftsartikel (refereegranskat)abstract
- Treatment of carbapenemase-producing Enterobacterales bloodstream infections in solid organ transplant recipients is challenging. The objective of this study was to develop a specific score to predict mortality in solid organ transplant recipients with carbapenemase-producing Enterobacterales bloodstream infections. A multinational, retrospective (2004-2016) cohort study (INCREMENT-SOT, ClinicalTrials.gov NCT02852902) was performed. The main outcome variable was 30-day all-cause mortality. The INCREMENT-SOT-CPE score was developed using logistic regression. The global cohort included 216 patients. The final logistic regression model included the following variables: INCREMENT-CPE mortality score >= 8 (8 points), no source control (3 points), inappropriate empirical therapy (2 points), cytomegalovirus disease (7 points), lymphopenia (4 points), and the interaction between INCREMENT-CPE score >= 8 and CMV disease (minus 7 points). This score showed an area under the receiver operating characteristic curve of 0.82 (95% confidence interval [CI] 0.76-0.88) and classified patients into 3 strata: 0-7 (low mortality), 8-11 (high mortality), and 12-17 (very-high mortality). We performed a stratified analysis of the effect of monotherapy vs combination therapy among 165 patients who received appropriate therapy. Monotherapy was associated with higher mortality only in the very-high (adjusted hazard ratio [HR] 2.82, 95% CI 1.13-7.06, P = .03) and high (HR 9.93, 95% CI 2.08-47.40, P = .004) mortality risk strata. A score-based algorithm is provided for therapy guidance.
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| 24. |
- 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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| 25. |
- Iram, T., et al.
(författare)
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Young CSF restores oligodendrogenesis and memory in aged mice via Fgf17
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 605, s. 509-515
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Tidskriftsartikel (refereegranskat)abstract
- Recent understanding of how the systemic environment shapes the brain throughout life has led to numerous intervention strategies to slow brain ageing(1-3). Cerebrospinal fluid (CSF) makes up the immediate environment of brain cells, providing them with nourishing compounds(4,5). We discovered that infusing young CSF directly into aged brains improves memory function. Unbiased transcriptome analysis of the hippocampus identified oligodendrocytes to be most responsive to this rejuvenated CSF environment. We further showed that young CSF boosts oligodendrocyte progenitor cell (OPC) proliferation and differentiation in the aged hippocampus and in primary OPC cultures. Using SLAMseq to metabolically label nascent mRNA, we identified serum response factor (SRF), a transcription factor that drives actin cytoskeleton rearrangement, as a mediator of OPC proliferation following exposure to young CSF. With age, SRF expression decreases in hippocampal OPCs, and the pathway is induced by acute injection with young CSF. We screened for potential SRF activators in CSF and found that fibroblast growth factor 17 (Fgf17) infusion is sufficient to induce OPC proliferation and long-term memory consolidation in aged mice while Fgf17 blockade impairs cognition in young mice. These findings demonstrate the rejuvenating power of young CSF and identify Fgf17 as a key target to restore oligodendrocyte function in the ageing brain.
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| 26. |
- Lekka, E, et al.
(författare)
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Pharmacological inhibition of Lin28 promotes ketogenesis and restores lipid homeostasis in models of non-alcoholic fatty liver disease
- 2022
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 7940-
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Tidskriftsartikel (refereegranskat)abstract
- Lin28 RNA-binding proteins are stem-cell factors that play key roles in development. Lin28 suppresses the biogenesis of let-7 microRNAs and regulates mRNA translation. Notably, let-7 inhibits Lin28, establishing a double-negative feedback loop. The Lin28/let-7 axis resides at the interface of metabolic reprogramming and oncogenesis and is therefore a potential target for several diseases. In this study, we use compound-C1632, a drug-like Lin28 inhibitor, and show that the Lin28/let-7 axis regulates the balance between ketogenesis and lipogenesis in liver cells. Hence, Lin28 inhibition activates synthesis and secretion of ketone bodies whilst suppressing lipogenesis. This occurs at least partly via let-7-mediated inhibition of nuclear receptor co-repressor 1, which releases ketogenesis gene expression mediated by peroxisome proliferator-activated receptor-alpha. In this way, small-molecule Lin28 inhibition protects against lipid accumulation in multiple cellular and male mouse models of hepatic steatosis. Overall, this study highlights Lin28 inhibitors as candidates for the treatment of hepatic disorders of abnormal lipid deposition.
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| 27. |
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| 28. |
- Iyer, Nirmal, et al.
(författare)
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The design and performance of the XL-Calibur anticoincidence shield
- 2023
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 1048
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Tidskriftsartikel (refereegranskat)abstract
- The XL-Calibur balloon-borne hard X-ray polarimetry mission comprises a Compton-scattering polarimeter placed at the focal point of an X-ray mirror. The polarimeter is housed within a BGO anticoincidence shield, which is needed to mitigate the considerable background radiation present at the observation altitude of -40 km. This paper details the design, construction and testing of the anticoincidence shield, as well as the performance measured during the week-long maiden flight from Esrange Space Centre to the Canadian Northwest Territories in July 2022. The in-flight performance of the shield followed design expectations, with a veto threshold <100 keV and a measured background rate of -0.5 Hz (20-40 keV). This is compatible with the scientific goals of the mission, where %-level minimum detectable polarisation is sought for a Hz-level source rate.
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| 29. |
- Sanneving, Linda, et al.
(författare)
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Health system capacity : maternal health policy implementation in the state of Gujarat, India
- 2013
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Ingår i: Global Health Action. - 1654-9716 .- 1654-9880. ; 6, s. 19629-
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The Government of Gujarat has for the past couple of decades continuously initiated several interventions to improve access to care for pregnant and delivering women within the state. Data from the last District Family Heath survey in Gujarat in 2007-2008 show that 56.4% of women had institutional deliveries and 71.5% had at least one antenatal check-up, indicating that challenges remain in increasing use of and access to maternal health care services.Objective: To explore the perceptions of high-level stakeholders on the process of implementing maternal health interventions in Gujarat. Method: Using the policy triangle framework developed by Walt and Gilson, the process of implementation was approached using in-depth interviews and qualitative content analysis.Result: Based on the analysis, three themes were developed: lack of continuity; the complexity of coordination; and lack of confidence and underutilization of the monitoring system. The findings suggest that decisions made and actions advocated and taken are more dependent on individual actors than on sustainable structures. The findings also indicate that the context in which interventions are implemented is challenged in terms of weak coordination and monitoring systems that are not used to evaluate and develop interventions on maternal health.Conclusions: The implementation of interventions on maternal health is dependent on the capacity of the health system to implement evidence-based policies. The capacity of the health system in Gujarat to facilitate implementation of maternal health interventions needs to be improved, both in terms of the role of actors and in terms of structures and processes.
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| 30. |
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| 31. |
- Xie, Shao-Hua, et al.
(författare)
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Association between levels of sex hormones and risk of esophageal adenocarcinoma and Barrett’s esophagus
- 2019
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Ingår i: Clinical Gastroenterology and Hepatology. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 1542-3565. ; 18:12, s. 2701-
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Esophageal adenocarcinoma (EAC) occurs most frequently in men. We performed a Mendelian randomization analysis to investigate whether genetic factors that regulate levels of sex hormones associated with risk of EAC or Barrett’s esophagus (BE). Methods: We conducted a Mendelian randomization analysis using data from patients with EAC (n=2488) or BE (n=3247) and control participants (n=2127), included in international consortia of genome-wide association studies in Australia, Europe, and North America. Genetic risk scores or single nucleotide variants were used as instrumental variables for 9 specific sex hormones. Logistic regression provided odds ratios (ORs) with 95% CIs. Results: Higher genetically predicted levels of follicle stimulating hormones were associated with increased risks of EAC and/or BE in men (OR, 1.14 per allele increase; 95% CI, 1.01- 1.27) and in women (OR, 1.28; 95% CI, 1.03-1.59). Higher predicted levels of luteinizing hormone were associated with a decreased risk of EAC in men (OR, 0.92 per standard deviation increase; 95% CI, 0.87-0.99) and in women (OR, 0.93; 95% CI, 0.79-1.09), and decreased risks of BE (OR, 0.88; 95% CI, 0.77-0.99) and EAC and/or BE (OR, 0.89; 95% CI, 0.79-1.00) in women. We found no clear associations for other hormones studied, including sex hormone-binding globulin, dehydroepiandrosterone sulphate, testosterone, dihydrotestosterone, estradiol, progesterone, or free androgen index. Conclusions: In a Mendelian randomization analysis of data from patients with EAC or BE, we found an association between genetically predicted levels of follicle stimulating and luteinizing hormones and risk of BE and EAC.
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| 32. |
- Aoyagi, M., et al.
(författare)
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Systematic effects on a Compton polarimeter at the focus of an X-ray mirror
- 2024
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Ingår i: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 158
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Tidskriftsartikel (refereegranskat)abstract
- XL-Calibur is a balloon-borne Compton polarimeter for X-rays in the ∼15–80 keV range. Using an X-ray mirror with a 12 m focal length for collecting photons onto a beryllium scattering rod surrounded by CZT detectors, a minimum-detectable polarization as low as ∼3% is expected during a 24-hour on-target observation of a 1 Crab source at 45° elevation. Systematic effects alter the reconstructed polarization as the mirror focal spot moves across the beryllium scatterer, due to pointing offsets, mechanical misalignment or deformation of the carbon-fiber truss supporting the mirror and the polarimeter. Unaddressed, this can give rise to a spurious polarization signal for an unpolarized flux, or a change in reconstructed polarization fraction and angle for a polarized flux. Using bench-marked Monte-Carlo simulations and an accurate mirror point-spread function characterized at synchrotron beam-lines, systematic effects are quantified, and mitigation strategies discussed. By recalculating the scattering site for a shifted beam, systematic errors can be reduced from several tens of percent to the few-percent level for any shift within the scattering element. The treatment of these systematic effects will be important for any polarimetric instrument where a focused X-ray beam is impinging on a scattering element surrounded by counting detectors.
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| 33. |
- Artomov, Mykyta, et al.
(författare)
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Rare variant, gene-based association study of hereditary melanoma using whole-exome sequencing
- 2017
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 109:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Extraordinary progress has been made in our understanding of common variants in many diseases, including melanoma. Because the contribution of rare coding variants is not as well characterized, we performed an exome-wide, gene-based association study of familial cutaneous melanoma (CM) and ocular melanoma (OM). Methods: Using 11 990 jointly processed individual DNA samples, whole-exome sequencing was performed, followed by largescale joint variant calling using GATK (Genome Analysis ToolKit). PLINK/SEQ was used for statistical analysis of genetic variation. Fourmodels were used to estimate the association among different types of variants. In vitro functional validation was performed using three humanmelanoma cell lines in 2D and 3D proliferation assays. In vivo tumor growth was assessed using xenografts of humanmelanoma A375melanoma cells in nudemice (eightmice per group). All statistical tests were two-sided. Results: Strong signals were detected for CDKN2A (Pmin = 6.16×10-8) in the CM cohort (n=273) and BAP1 (Pmin = 3.83×10-6) in the OM (n=99) cohort. Eleven genes that exhibited borderline association (P < 10-4) were independently validated using The Cancer Genome Atlas melanoma cohort (379 CM, 47 OM) and a matched set of 3563 European controls with CDKN2A (P = .009), BAP1 (P = .03), and EBF3 (P = 4.75×10-4), a candidate risk locus, all showing evidence of replication. EBF3 was then evaluated using germline data from a set of 132 familial melanoma cases and 4769 controls of UK origin (joint P = 1.37×10-5). Somatically, loss of EBF3 expression correlated with progression, poorer outcome, and high MITF tumors. Functionally, induction of EBF3 in melanoma cells reduced cell growth in vitro, retarded tumor formation in vivo, and reduced MITF levels. Conclusions: The results of this large rare variant germline association study further define the mutational landscape of hereditary melanoma and implicate EBF3 as a possible CM predisposition gene.
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| 34. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 35. |
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| 36. |
- Garcia, YR, et al.
(författare)
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Cyclodextrin-peptide conjugates for sequence specific DNA binding
- 2015
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Ingår i: Organic & biomolecular chemistry. - : Royal Society of Chemistry (RSC). - 1477-0539 .- 1477-0520. ; 13:18, s. 5273-5278
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Tidskriftsartikel (refereegranskat)abstract
- CD–peptide conjugates were synthesized via CuAAC. Though the CD cavity size was shown to influence the binding affinity of the compounds, all constructs recognize and bind the cognate CRE dsDNA.
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| 37. |
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| 38. |
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| 39. |
- Ivanics, Tommy, et al.
(författare)
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Impact of the acuity circle model for liver allocation on multivisceral transplant candidates
- 2022
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Ingår i: American Journal of Transplantation. - : John Wiley & Sons. - 1600-6135 .- 1600-6143. ; 22:2, s. 464-473
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Tidskriftsartikel (refereegranskat)abstract
- Liver allocation was updated on February 4, 2020, replacing a Donor Service Area (DSA) with acuity circles (AC). The impact on waitlist outcomes for patients listed for combined liver-intestine transplantation (multivisceral transplantation [MVT]) remains unknown. The Organ Procurement and Transplantation Network/United Network for Organ Sharing database was used to identify all candidates listed for both liver and intestine between January 1, 2018 and March 5, 2021. Two eras were defined: pre-AC (2018–2020) and post-AC (2020–2021). Outcomes included 90-day waitlist mortality and transplant probability. A total of 127 adult and 104 pediatric MVT listings were identified. In adults, the 90-day waitlist mortality was not statistically significantly different, but transplant probability was lower post-AC. After risk-adjustment, post-AC was associated with a higher albeit not statistically significantly different mortality hazard (sub-distribution hazard ratio[sHR]: 8.45, 95% CI: 0.96–74.05; p = .054), but a significantly lower transplant probability (sHR: 0.33, 95% CI: 0.15–0.75; p = .008). For pediatric patients, waitlist mortality and transplant probability were similar between eras. The proportion of patients who underwent transplant with exception points was lower post-AC both in adult (44% to 9%; p = .04) and pediatric recipients (65% to 15%; p = .002). A lower transplant probability observed in adults listed for MVT may ultimately result in increased waitlist mortality. Efforts should be taken to ensure equitable organ allocation in this vulnerable patient population.
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| 40. |
- Lee, Ben H, et al.
(författare)
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Highly functionalized organic nitrates in the southeast United States: Contribution to secondary organic aerosol and reactive nitrogen budgets.
- 2016
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 113:6, s. 1516-21
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Tidskriftsartikel (refereegranskat)abstract
- Speciated particle-phase organic nitrates (pONs) were quantified using online chemical ionization MS during June and July of 2013 in rural Alabama as part of the Southern Oxidant and Aerosol Study. A large fraction of pONs is highly functionalized, possessing between six and eight oxygen atoms within each carbon number group, and is not the common first generation alkyl nitrates previously reported. Using calibrations for isoprene hydroxynitrates and the measured molecular compositions, we estimate that pONs account for 3% and 8% of total submicrometer organic aerosol mass, on average, during the day and night, respectively. Each of the isoprene- and monoterpenes-derived groups exhibited a strong diel trend consistent with the emission patterns of likely biogenic hydrocarbon precursors. An observationally constrained diel box model can replicate the observed pON assuming that pONs (i) are produced in the gas phase and rapidly establish gas-particle equilibrium and (ii) have a short particle-phase lifetime (∼2-4 h). Such dynamic behavior has significant implications for the production and phase partitioning of pONs, organic aerosol mass, and reactive nitrogen speciation in a forested environment.
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| 41. |
- Lopez-Hilfiker, F D, et al.
(författare)
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Molecular Composition and Volatility of Organic Aerosol in the Southeastern U.S.: Implications for IEPOX Derived SOA.
- 2016
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Ingår i: Environmental science & technology. - : American Chemical Society (ACS). - 1520-5851 .- 0013-936X. ; 50:5, s. 2200-2209
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Tidskriftsartikel (refereegranskat)abstract
- We present measurements as part of the Southern Oxidant and Aerosol Study (SOAS) during which atmospheric aerosol particles were comprehensively characterized. We present results utilizing a Filter Inlet for Gases and AEROsol coupled to a chemical ionization mass spectrometer (CIMS). We focus on the volatility and composition of isoprene derived organic aerosol tracers and of the bulk organic aerosol. By utilizing the online volatility and molecular composition information provided by the FIGAERO-CIMS, we show that the vast majority of commonly reported molecular tracers of isoprene epoxydiol (IEPOX) derived secondary organic aerosol (SOA) is derived from thermal decomposition of accretion products or other low volatility organics having effective saturation vapor concentrations <10(-3) μg m(-3). In addition, while accounting for up to 30% of total submicrometer organic aerosol mass, the IEPOX-derived SOA has a higher volatility than the remaining bulk. That IEPOX-SOA, and more generally bulk organic aerosol in the Southeastern U.S. is comprised of effectively nonvolatile material has important implications for modeling SOA derived from isoprene, and for mechanistic interpretations of molecular tracer measurements. Our results show that partitioning theory performs well for 2-methyltetrols, once accretion product decomposition is taken into account. No significant partitioning delays due to aerosol phase or viscosity are observed, and no partitioning to particle-phase water or other unexplained mechanisms are needed to explain our results.
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| 42. |
- Mehta, Vihang, et al.
(författare)
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A Spatially Resolved Analysis of Star Formation Burstiness by Comparing UV and Hα in Galaxies at z ∼ 1 with UVCANDELS
- 2023
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 952:2
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Tidskriftsartikel (refereegranskat)abstract
- The UltraViolet imaging of the Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey Fields (UVCANDELS) program provides Hubble Space Telescope (HST)/UVIS F275W imaging for four CANDELS fields. We combine this UV imaging with existing HST/near-IR grism spectroscopy from 3D-HST+AGHAST to directly compare the resolved rest-frame UV and Hα emission for a sample of 979 galaxies at 0.7 < z < 1.5, spanning a range in stellar mass of 108−11.5M⊙. Using a stacking analysis, we perform a resolved comparison between homogenized maps of rest-UV and Hα to compute the average UV-to-Hα luminosity ratio (an indicator of burstiness in star formation) as a function of galactocentric radius. We find that galaxies below stellar mass of ∼109.5M⊙, at all radii, have a UV-to-Hα ratio higher than the equilibrium value expected from constant star formation, indicating a significant contribution from bursty star formation. Even for galaxies with stellar mass ≳109.5M⊙, the UV-to-Hα ratio is elevated toward their outskirts (R/Reff > 1.5), suggesting that bursty star formation is likely prevalent in the outskirts of even the most massive galaxies, but is likely overshadowed by their brighter cores. Furthermore, we present the UV-to-Hα ratio as a function of galaxy surface brightness, a proxy for stellar mass surface density, and find that regions below ∼107.5M⊙ kpc−2 are consistent with bursty star formation, regardless of their galaxy stellar mass, potentially suggesting that local star formation is independent of global galaxy properties at the smallest scales. Last, we find galaxies at z > 1.1 to have bursty star formation, regardless of radius or surface brightness.
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| 43. |
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| 44. |
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| 45. |
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| 46. |
- van der Valk, Eline S., et al.
(författare)
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In adults with obesity, copeptin is linked with BMI but is not associated with long-term exposure to cortisol and cortisone
- 2020
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Ingår i: European Journal of Endocrinology. - 1479-683X. ; 183:6, s. 669-676
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Tidskriftsartikel (refereegranskat)abstract
- Context: Obesity and cardiometabolic diseases are associated with higher long-term glucocorticoid levels, measured as scalp hair cortisol (HairF) and cortisone (HairE). Cardiometabolic diseases have also been associated with copeptin, a stable surrogate marker for the arginine-vasopressin (AVP) system. Since AVP is, together with corticotropin-releasing hormone (CRH) an important regulator of the hypothalamic-pituitary adrenal axis (HPA axis), we hypothesize that AVP contributes to chronic hypercortisolism in obesity. Objective: To investigate whether copeptin levels are associated with Higher HairF and HairE levels in obesity. Design: A cross-sectional study in 51 adults with obesity (BMI ≥30 kg/m2). Methods: Associations and interactions between copeptin, HairF, HairE, and cardiometabolic parameters were cross-sectionally analyzed. Results: Copeptin was strongly associated with BMI and waist circumference (WC) (rho = 0.364 and 0.530, P = 0.008 and <0.001, respectively), also after correction for confounders. There were no associations between copeptin and HairF or HairE on a continuous or dichotomized scale, despite correction for confounders. Conclusion: In patients with obesity, AVP seems not a major contributor to the frequently observed high cortisol levels. Other factors which stimulate the HPA axis or affect cortisol synthesis or breakdown may be more important than the influence of AVP on long-term glucocorticoid levels in obesity.
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| 47. |
- Wimberger, Sandra, 1987, et al.
(författare)
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Simultaneous inhibition of DNA-PK and Pol ϴ improves integration efficiency and precision of genome editing
- 2023
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Ingår i: Nature Communications. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Genome editing, specifically CRISPR/Cas9 technology, has revolutionized biomedical research and offers potential cures for genetic diseases. Despite rapid progress, low efficiency of targeted DNA integration and generation of unintended mutations represent major limitations for genome editing applications caused by the interplay with DNA double-strand break repair pathways. To address this, we conduct a large-scale compound library screen to identify targets for enhancing targeted genome insertions. Our study reveals DNA-dependent protein kinase (DNA-PK) as the most effective target to improve CRISPR/Cas9-mediated insertions, confirming previous findings. We extensively characterize AZD7648, a selective DNA-PK inhibitor, and find it to significantly enhance precise gene editing. We further improve integration efficiency and precision by inhibiting DNA polymerase theta (Pol ϴ). The combined treatment, named 2iHDR, boosts templated insertions to 80% efficiency with minimal unintended insertions and deletions. Notably, 2iHDR also reduces off-target effects of Cas9, greatly enhancing the fidelity and performance of CRISPR/Cas9 gene editing. Low efficiency of target DNA integration remains a challenge in genome engineering. Here the authors perform large-scale compound library and genetic screens to identify targets that enhance gene editing: they see that combined DNA-PK and Pol ϴ inhibition with potent compounds increases editing efficiency and precision.
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| 48. |
- Abarr, Q., et al.
(författare)
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Performance of the X-Calibur hard X-ray polarimetry mission during its 2018/19 long-duration balloon flight
- 2022
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Ingår i: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 143, s. 102749-
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Tidskriftsartikel (refereegranskat)abstract
- X-Calibur is a balloon-borne telescope that measures the polarization of high-energy X-rays in the 15-50 keV energy range. The instrument makes use of the fact that X-rays scatter preferentially perpendicular to the polarization direction. A beryllium scattering element surrounded by pixellated CZT detectors is located at the focal point of the InFOC mu S hard X-ray mirror. The instrument was launched for a long-duration balloon (LDB) flight from McMurdo (Antarctica) on December 29, 2018, and obtained the first constraints of the hard X-ray polarization of an accretion-powered pulsar. Here, we describe the characterization and calibration of the instrument on the ground and its performance during the flight, as well as simulations of particle backgrounds and a comparison to measured rates. The pointing system and polarimeter achieved the excellent projected performance. The energy detection threshold for the anticoincidence system was found to be higher than expected and it exhibited unanticipated dead time. Both issues will be remedied for future flights. Overall, the mission performance was nominal, and results will inform the design of the follow-up mission XL-Calibur, which is scheduled to be launched in summer 2022.
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| 49. |
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