| 1. |
- Wang, Anqi, et al.
(författare)
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Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
- 2023
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:12, s. 2065-2074
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Tidskriftsartikel (refereegranskat)abstract
- The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
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| 2. |
- 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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| 3. |
- Conti, David, V, et al.
(författare)
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Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
- 2021
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:1, s. 65-75
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction. A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.
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| 4. |
- Kassebaum, Nicholas J., et al.
(författare)
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Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990-2015 : 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. 1603-1658
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Tidskriftsartikel (refereegranskat)abstract
- Background Healthy life expectancy (HALE) and disability-adjusted life-years (DALYs) provide summary measures of health across geographies and time that can inform assessments of epidemiological patterns and health system performance, help to prioritise investments in research and development, and monitor progress toward the Sustainable Development Goals (SDGs). We aimed to provide updated HALE and DALYs for geographies worldwide and evaluate how disease burden changes with development. Methods We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2015. We calculated DALYs by summing years of life lost (YLLs) and years of life lived with disability (YLDs) for each geography, age group, sex, and year. We estimated HALE using the Sullivan method, which draws from age-specific death rates and YLDs per capita. We then assessed how observed levels of DALYs and HALE differed from expected trends calculated with the Socio-demographic Index (SDI), a composite indicator constructed from measures of income per capita, average years of schooling, and total fertility rate. Findings Total global DALYs remained largely unchanged from 1990 to 2015, with decreases in communicable, neonatal, maternal, and nutritional (Group 1) disease DALYs off set by increased DALYs due to non-communicable diseases (NCDs). Much of this epidemiological transition was caused by changes in population growth and ageing, but it was accelerated by widespread improvements in SDI that also correlated strongly with the increasing importance of NCDs. Both total DALYs and age-standardised DALY rates due to most Group 1 causes significantly decreased by 2015, and although total burden climbed for the majority of NCDs, age-standardised DALY rates due to NCDs declined. Nonetheless, age-standardised DALY rates due to several high-burden NCDs (including osteoarthritis, drug use disorders, depression, diabetes, congenital birth defects, and skin, oral, and sense organ diseases) either increased or remained unchanged, leading to increases in their relative ranking in many geographies. From 2005 to 2015, HALE at birth increased by an average of 2.9 years (95% uncertainty interval 2.9-3.0) for men and 3.5 years (3.4-3.7) for women, while HALE at age 65 years improved by 0.85 years (0.78-0.92) and 1.2 years (1.1-1.3), respectively. Rising SDI was associated with consistently higher HALE and a somewhat smaller proportion of life spent with functional health loss; however, rising SDI was related to increases in total disability. Many countries and territories in central America and eastern sub-Saharan Africa had increasingly lower rates of disease burden than expected given their SDI. At the same time, a subset of geographies recorded a growing gap between observed and expected levels of DALYs, a trend driven mainly by rising burden due to war, interpersonal violence, and various NCDs. Interpretation Health is improving globally, but this means more populations are spending more time with functional health loss, an absolute expansion of morbidity. The proportion of life spent in ill health decreases somewhat with increasing SDI, a relative compression of morbidity, which supports continued efforts to elevate personal income, improve education, and limit fertility. Our analysis of DALYs and HALE and their relationship to SDI represents a robust framework on which to benchmark geography-specific health performance and SDG progress. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform financial and research investments, prevention efforts, health policies, and health system improvement initiatives for all countries along the development continuum.
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| 5. |
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| 6. |
- 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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| 7. |
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| 8. |
- Abbafati, Cristiana, et al.
(författare)
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- 2020
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Tidskriftsartikel (refereegranskat)
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| 9. |
- Abdelmalek, George, et al.
(författare)
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Intercostal nerve transfer for biceps reinnervation in obstetrical brachial plexus palsy : a preferred reporting items for systematic reviews and meta-analysis for individual patient data systematic review using individualized fusion and comparison to supraclavicular exploration and nerve grafting
- 2024
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Ingår i: Journal of Children's Orthopaedics. - : Sage Publications. - 1863-2521 .- 1863-2548. ; 18:1, s. 54-63
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Forskningsöversikt (refereegranskat)abstract
- Introduction: The objective of this study was to search existing literature on nerve reconstruction surgery in patients with obstetric brachial plexus palsy to determine whether treatment with supraclavicular exploration and nerve grafting produced better elbow flexion outcomes compared to intercostal nerve transfer.Methods: This study was a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis for Individual Patient Data guidelines. A systematic search was conducted using multiple databases. An ordinal regression model was used to analyze the effect of using supraclavicular exploration and nerve grafting or intercostal nerve on elbow flexion with the two scores measured: elbow flexion Medical Research Council scores and Toronto active movements scale scores for elbow flexion.Results: A final patient database from 6 published articles consisted of 83 supraclavicular exploration and nerve grafting patients (73 patients with Medical Research Council and 10 patients with Toronto score) and 7 published articles which consisted of 131 intercostal nerve patients (84 patients with Medical Research Council and 47 patients with Toronto scores). Patients who underwent supraclavicular exploration and nerve grafting presented with an average Medical Research Council score of 3.9 ± 0.72 and an average Toronto score of 6.2 ± 2.2. Patients who underwent intercostal nerve transfer presented with an average Medical Research Council score of 3.9 ± 0.71 and an average Toronto score of 6.4 ± 1.2. There was no statistical difference between supraclavicular exploration and nerve grafting and intercostal nerve transfer when utilizing Medical Research Council elbow flexion scores (ordinal regression: 0.3821, standard error: 0.4590, p = 0.2551) or Toronto Active Movement Scale score for elbow flexion (ordinal regression: 0.7154, standard error: 0.8487, p = 0.2188).Conclusion: Regardless of surgical intervention utilized (supraclavicular exploration and nerve grafting or intercostal nerve transfers), patients had excellent outcomes for elbow flexion following obstetric brachial plexus palsy when utilizing Medical Research Council or Toronto scores for elbow flexion. The difference between these scores was not statistically significant.Type of study/Level of evidence: Therapeutic Study: Investigating the Result of Treatment/level III.
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| 10. |
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| 11. |
- Mahajan, Anubha, et al.
(författare)
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Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
- 2022
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
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Tidskriftsartikel (refereegranskat)abstract
- We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
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| 12. |
- Mendiratta, Dhruv, et al.
(författare)
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Educational quality of YouTube content on brachial plexus injury and treatment
- 2024
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Ingår i: Microsurgery. - : John Wiley & Sons. - 0738-1085 .- 1098-2752. ; :1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: While surgical literature exists on birth-related brachial plexus injury (BPI), there are not validated sources of information on BPI for patients, which can impact patient autonomy and decision-making. With YouTube as a popular source for patients to research diagnoses, this study aims to evaluate the quality of information regarding BPI and its treatment available on the platform.Materials and Methods: BPI YouTube videos were screened independently by two reviewers. Videos were categorized by source: (1) academic, government, and non-profit organizations; (2) private practices, companies, and for-profit organizations; (3) independent users. Each video was evaluated for reliability, credibility, and quality using the modified DISCERN criteria (scale, 0–5), Journal of the American Medical Association (JAMA) criteria (scale, 0–4), and Global Quality Scale (GQS; scale, 1–5). Surgical treatment videos were analyzed by the senior author using a modified “treatment” DISCERN criteria (scale, 8–40). Non-English videos were excluded from this study. Analysis of variance tests were used to compare means.Results: One hundred and fifteen videos were selected for final analysis. The mean modified DISCERN score was 3.26; JAMA was 2.31; GQS was 3.48. Videos were subdivided according to source. Group 1, 2, and 3 had 45, 24, and 46 videos, respectively. Modified DISCERN score was greater for Group 1 than Group 2 (3.58 vs. 3.04, p <.001) and Group 3 (3.58 vs. 3.07, p <.001). JAMA score was greater for Group 1 than Group 2 (2.63 vs 2.15, p =.041) and Group 3 (2.63 vs. 2.08, p =.002). GQS score was greater for Group 1 than Group 2 (3.93 vs. 3.31, p =.031) and Group 3 (3.93 vs. 3.13, p <.001). Of the 34 videos (44.7%) that mentioned treatment, the DISCERN score was 14.32.Conclusion: The videos analyzed were found to have moderate reliability, credibility, and quality. The reliability of information regarding treatments for BPI was poor. Healthcare providers should supply additional information on treatment of BPI.
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| 13. |
- Pilla, Rachel M., et al.
(författare)
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Deeper waters are changing less consistently than surface waters in a global analysis of 102 lakes
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Globally, lake surface water temperatures have warmed rapidly relative to air temperatures, but changes in deepwater temperatures and vertical thermal structure are still largely unknown. We have compiled the most comprehensive data set to date of long-term (1970–2009) summertime vertical temperature profiles in lakes across the world to examine trends and drivers of whole-lake vertical thermal structure. We found significant increases in surface water temperatures across lakes at an average rate of + 0.37 °C decade−1, comparable to changes reported previously for other lakes, and similarly consistent trends of increasing water column stability (+ 0.08 kg m−3 decade−1). In contrast, however, deepwater temperature trends showed little change on average (+ 0.06 °C decade−1), but had high variability across lakes, with trends in individual lakes ranging from − 0.68 °C decade−1 to + 0.65 °C decade−1. The variability in deepwater temperature trends was not explained by trends in either surface water temperatures or thermal stability within lakes, and only 8.4% was explained by lake thermal region or local lake characteristics in a random forest analysis. These findings suggest that external drivers beyond our tested lake characteristics are important in explaining long-term trends in thermal structure, such as local to regional climate patterns or additional external anthropogenic influences.
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| 14. |
- Pilla, Rachel M., et al.
(författare)
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Global data set of long-term summertime vertical temperature profiles in 153 lakes
- 2021
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Ingår i: Scientific Data. - : Springer Nature. - 2052-4463. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Climate change and other anthropogenic stressors have led to long-term changes in the thermal structure, including surface temperatures, deepwater temperatures, and vertical thermal gradients, in many lakes around the world. Though many studies highlight warming of surface water temperatures in lakes worldwide, less is known about long-term trends in full vertical thermal structure and deepwater temperatures, which have been changing less consistently in both direction and magnitude. Here, we present a globally-expansive data set of summertime in-situ vertical temperature profiles from 153 lakes, with one time series beginning as early as 1894. We also compiled lake geographic, morphometric, and water quality variables that can influence vertical thermal structure through a variety of potential mechanisms in these lakes. These long-term time series of vertical temperature profiles and corresponding lake characteristics serve as valuable data to help understand changes and drivers of lake thermal structure in a time of rapid global and ecological change.
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| 15. |
- Shafei, Jasmine, et al.
(författare)
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Trends of age and geographical location in microsurgical treatment of obstetric brachial plexus palsy
- 2022
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Ingår i: Bulletin of the Hospital for Joint Diseases. - : J. Michael Ryan Publishing. - 2328-4633 .- 2328-5273. ; 80:2, s. 195-199
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Tidskriftsartikel (refereegranskat)abstract
- Background: Debate over the optimal age at time of surgery for treatment of brachial plexus birth injury (BPBI) remains controversial, and there exists geographical variation in surgical preference for age at time of surgery. The objective of this review was to analyze trends in age and geography in brachial plexus microsurgery for treatment of brachial plexus birth injury (BPBI) over time.Methods: Review of the literature in this study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. PubMed, Cochrane, Web of Science, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases were searched.Results: Pediatric patients undergoing brachial plexus microsurgery described in published reports before 2011 had a mean of 7.15 ± 6.56 months of age, while pediatric patients undergoing brachial plexus microsurgery surgery described in published reports after 2011 had a mean of 11.23 ± 9.76 months of age (p < 0.05). The mean age at surgery was lower in publications from Asian countries (6.29 months) than in publications from North America (11.34 months; p <0.05).Conclusions: Age at time of microsurgery for treatment of BPBI is increasing, with mean age at surgeries occurring in and after 2011 being 4 months higher than thos occuring before 2011. The mean age at surgery was about 5 months higher in North American publications than in Asian publications.
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| 16. |
- Srinivasan, Nivetha, et al.
(författare)
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Surgical timing in neonatal brachial plexus palsy : A PRISMA-IPD systematic review
- 2022
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Ingår i: Microsurgery. - : John Wiley & Sons. - 0738-1085 .- 1098-2752. ; 42:4, s. 381-390
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Forskningsöversikt (refereegranskat)abstract
- Background: Neonatal brachial plexus palsy (NBPP) is a serious complication of high-risk deliveries with controversy surrounding timing of corrective nerve surgery. This review systematically examines the existing literature and investigates correlations between age at time of upper trunk brachial plexus microsurgery and surgical outcomes.Methods: A systematic screening of PubMed, Cochrane, Web of Science, and CINAHL databases using PRISMA-IPD guidelines was conducted in January 2020 to include full-text English papers with microsurgery in upper trunk palsy, pediatric patients. Spearman rank correlation analysis and two-tailed t-tests were performed using individual patient data to determine the relationship between mean age at time of surgery and outcome as determined by the Mallet, Medical Research Council (MRC), or Active Movement Scale (AMS) subscores.Results: Two thousand nine hundred thirty six papers were screened to finalize 25 papers containing individual patient data (n = 256) with low to moderate risk of bias, as assessed by the ROBINS-I assessment tool. Mallet subscore for hand-to-mouth and shoulder abduction, AMS subscore for elbow flexion and external rotation, and MRC subscore for elbow flexion were analyzed alongside the respective age of patients at surgery. Spearman rank correlation analysis revealed a significant negative correlation (ρ = −0.30, p <.01, n = 89) between increasing age (5.50 ± 2.09 months) and Mallet subscore for hand-to-mouth (3.43 ± 0.83). T-tests revealed a significant decrease in Mallet hand-to-mouth subscores after 6 months (p <.05) and 9 months (p <.05) of age. No significant effects were observed for Mallet shoulder abduction, MRC elbow flexion, or AMS elbow flexion and external rotation.Conclusion: The cumulative evidence suggests a significant negative correlation between age at microsurgery and Mallet subscores for hand-to-mouth. However, a similar correlation with age at surgery was not observed for Mallet shoulder abduction, MRC elbow flexion, AMS external rotation, and AMS elbow flexion subscores.
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| 17. |
- Bhaduri, Anindya, et al.
(författare)
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Free energy calculation using space filled design and weighted reconstruction : a modified single sweep approach
- 2020
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Ingår i: Molecular Simulation. - : TAYLOR & FRANCIS LTD. - 0892-7022 .- 1029-0435. ; 46:3, s. 193-206
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Tidskriftsartikel (refereegranskat)abstract
- A modified single sweep approach is proposed for generating free energy landscapes. The approach replaces the use of temperature-accelerated molecular dynamics (TAMD) to generate centres in collective variable (CV) space at which mean forces are computed using restrained molecular dynamics (MD) simulations with a sequential space-filling design. This approach also modifies the radial basis function reconstruction step of the traditional single sweep approach and proposes a weighted reconstruction of the free energy surface using the previously generated mean forces. The modified approach is compared to the traditional single sweep (SS) approach on the (phi, psi) dihedral free-energy map of solvated alanine dipeptide (AD). It is found that the new approach results in a more accurate reconstructed free energy than does the traditional approach when compared to the directly-computed reference free energy landscape. It is shown that the increased accuracy of the overall map stems from the improved 1-dimensional space filling (projective) property of the proposed design compared to that of the TAMD generated centres. A further enhancement in the accuracy of the crucial lower energy regions is enabled by the introduction of weights in the reconstruction step that give more importance to lower energy-valued regions.
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| 18. |
- Bjelic, Sinisa, et al.
(författare)
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Computational design of enone-binding proteins with catalytic activity for the Morita-Baylis-Hillman reaction
- 2013
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Ingår i: ACS Chemical Biology. - : American Chemical Society (ACS). - 1554-8929 .- 1554-8937. ; 8:4, s. 749-757
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Tidskriftsartikel (refereegranskat)abstract
- The Morita-Baylis-Hillman reaction forms a carbon-carbon bond between the α-carbon of a conjugated carbonyl compound and a carbon electrophile. The reaction mechanism involves Michael addition of a nucleophile catalyst at the carbonyl β-carbon, followed by bond formation with the electrophile and catalyst disassociation to release the product. We used Rosetta to design 48 proteins containing active sites predicted to carry out this mechanism, of which two show catalytic activity by mass spectrometry (MS). Substrate labeling measured by MS and site-directed mutagenesis experiments show that the designed active-site residues are responsible for activity, although rate acceleration over background is modest. To characterize the designed proteins, we developed a fluorescence-based screen for intermediate formation in cell lysates, carried out microsecond molecular dynamics simulations, and solved X-ray crystal structures. These data indicate a partially formed active site and suggest several clear avenues for designing more active catalysts.
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| 19. |
- Gardner, Jasmine M., et al.
(författare)
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Energetics of Flap Opening in HIV-1 Protease : String Method Calculations
- 2019
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Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 123:45, s. 9584-9591
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Tidskriftsartikel (refereegranskat)abstract
- HIV-1 protease (PR) is the viral protein responsible for virion maturation, and its mechanisms of action remain incompletely understood. PR is dimeric and contains two flexible, symmetry-related flaps, which act as a gate to inhibit access to the binding pocket and hold the polypeptide substrate in the binding pocket once bound. Wide flap opening, a conformational change assumed to be necessary for substrate binding, is a rare event in the closed and bound form. In this study, we use molecular dynamics (MD) simulations and advanced MD techniques including temperature acceleration and string method in collective variables to study the conformational changes associated with substrate unbinding of both wild-type and F99Y mutant PR. The F99Y mutation is shown via MD to decouple the closing of previously unrecognized distal pockets from substrate unbinding. To determine whether or not the F99Y mutation affects the energetic cost of wide flap opening, we use string method in collective variables to determine the minimum free-energy mechanism for wide flap opening in concert with distal pocket closing. The results indicate that the major energetic cost in flap opening is disengagement of the two flap-tip Ile50 residues from each other and is not affected by the F99Y mutation.
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| 20. |
- Holman, Rury R, et al.
(författare)
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Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes.
- 2017
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 377:13, s. 1228-1239
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown.METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy.RESULTS: In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P<0.001 for noninferiority) but was not superior to placebo with respect to efficacy (P=0.06 for superiority). The rates of death from cardiovascular causes, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, hospitalization for heart failure, and hospitalization for acute coronary syndrome, and the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ significantly between the two groups.CONCLUSIONS: Among patients with type 2 diabetes with or without previous cardiovascular disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo. (Funded by Amylin Pharmaceuticals; EXSCEL ClinicalTrials.gov number, NCT01144338 .).
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| 21. |
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| 22. |
- Mokdad, Ali H., et al.
(författare)
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Diabetes mellitus and chronic kidney disease in the Eastern Mediterranean Region : findings from the Global Burden of Disease 2015 study
- 2018
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Ingår i: International Journal of Public Health. - : SPRINGER BASEL AG. - 1661-8556 .- 1661-8564. ; 63, s. 177-186
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Tidskriftsartikel (refereegranskat)abstract
- We used findings from the Global Burden of Disease 2015 study to update our previous publication on the burden of diabetes and chronic kidney disease due to diabetes (CKD-DM) during 1990-2015. We extracted GBD 2015 estimates for prevalence, mortality, and disability-adjusted life years (DALYs) of diabetes (including burden of low vision due to diabetes, neuropathy, and amputations and CKD-DM for 22 countries of the EMR from the GBD visualization tools. In 2015, 135,230 (95% UI 123,034-148,184) individuals died from diabetes and 16,470 (95% UI 13,977-18,961) from CKD-DM, 216 and 179% increases, respectively, compared to 1990. The total number of people with diabetes was 42.3 million (95% UI 38.6-46.4 million) in 2015. DALY rates of diabetes in 2015 were significantly higher than the expected rates based on Socio-demographic Index (SDI). Our study showed a large and increasing burden of diabetes in the region. There is an urgency in dealing with diabetes and its consequences, and these efforts should be at the forefront of health prevention and promotion.
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| 23. |
- Stavenow, Jasmine, et al.
(författare)
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Sowerby’s Beaked Whales (Mesoplodon bidens) in the Skagerrak and Adjacent Waters: Historical Records and Recent Post-Mortem Findings
- 2022
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Ingår i: Oceans. - : MDPI AG. - 2673-1924. ; 3:3, s. 250-267
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Tidskriftsartikel (refereegranskat)abstract
- In contrast to sparse historical observational records, five Sowerby’s beaked whales (SBW) stranded and died in Swedish waters between 2015 and 2020. Here we summarize historical records of SBWs in the Skagerrak basin and adjacent waters. The three recent stranding events from Sweden are described, and the post-mortem findings, including diet analysis, from the five SBWs are presented. Of 30 historical records of SBWs observations since 1869, 13 (43%) were documented between 2010 and 2021, and records between July and November were the most frequent. The recent stranding events occurred in October 2015 (n = 1), August 2019 (n = 3) and July 2020 (n = 1). Four of the SBWs were examined through necropsy, and one was sampled in the field. They were all sub-adults and included a single female and four males. The causes of death were emaciation, euthanasia due to traumatic injury, and live stranding of undetermined cause. Two SBWs each had a focal bone lesion consistent with osteomyelitis. Other findings included pox-like dermatitis, trauma, focal granulomas in a lymph node and intestine, and ulceration of the stomach. CT scans were performed on the heads of two animals, with inconclusive results. Three SBWs had hard parts in the gastrointestinal tract that mainly consisted of otoliths from several fish species. An eDNA-analysis confirmed and supplemented the diet analysis, revealing 17 fish species in total, including species not previously described as prey for SBW, such as Pleuronectidae spp. The apparent increase in observational records since 2010 may indicate a shift in SBW distribution or changing threats to these animals. Our results support and expand theories on SBW movements and provide data on the biology and health of this poorly known species, which are valuable for conservation and legislation efforts.
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