17 research outputs found
Measuring the metric: a parametrized post-Friedmanian approach to the cosmic dark energy problem
We argue for a ``parametrized post-Friedmanian'' approach to linear
cosmology, where the history of expansion and perturbation growth is measured
without assuming that the Einstein Field Equations hold. As an illustration, a
model-independent analysis of 92 type Ia supernovae demonstrates that the curve
giving the expansion history has the wrong shape to be explained without some
form of dark energy or modified gravity. We discuss how upcoming lensing,
galaxy clustering, cosmic microwave background and Lyman alpha forest
observations can be combined to pursue this program, which generalizes the
quest for a dark energy equation of state, and forecast the accuracy that the
proposed SNAP satellite can attain.Comment: Replaced to match accepted PRD version. References and another
example added, section III omitted since superceded by astro-ph/0207047. 11
PRD pages, 7 figs. Color figs and links at
http://www.hep.upenn.edu/~max/gravity.html or from [email protected]
Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021
This online publication has been
corrected. The corrected version
first appeared at thelancet.com
on September 28, 2023BACKGROUND : Diabetes is one of the leading causes of death and disability worldwide, and affects people regardless of country, age group, or sex. Using the most recent evidentiary and analytical framework from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD), we produced location-specific, age-specific, and sex-specific estimates of diabetes prevalence and burden from 1990 to 2021, the proportion of type 1 and type 2 diabetes in 2021, the proportion of the type 2 diabetes burden attributable to selected risk factors, and projections of diabetes prevalence through 2050. METHODS : Estimates of diabetes prevalence and burden were computed in 204 countries and territories, across 25 age groups, for males and females separately and combined; these estimates comprised lost years of healthy life, measured in disability-adjusted life-years (DALYs; defined as the sum of years of life lost [YLLs] and years lived with disability [YLDs]). We used the Cause of Death Ensemble model (CODEm) approach to estimate deaths due to diabetes, incorporating 25 666 location-years of data from vital registration and verbal autopsy reports in separate total (including both type 1 and type 2 diabetes) and type-specific models. Other forms of diabetes, including gestational and monogenic diabetes, were not explicitly modelled. Total and type 1 diabetes prevalence was estimated by use of a Bayesian meta-regression modelling tool, DisMod-MR 2.1, to analyse 1527 location-years of data from the scientific literature, survey microdata, and insurance claims; type 2 diabetes estimates were computed by subtracting type 1 diabetes from total estimates. Mortality and prevalence estimates, along with standard life expectancy and disability weights, were used to calculate YLLs, YLDs, and DALYs. When appropriate, we extrapolated estimates to a hypothetical population with a standardised age structure to allow comparison in populations with different age structures. We used the comparative risk assessment framework to estimate the risk-attributable type 2 diabetes burden for 16 risk factors falling under risk categories including environmental and occupational factors, tobacco use, high alcohol use, high body-mass index (BMI), dietary factors, and low physical activity. Using a regression framework, we forecast type 1 and type 2 diabetes prevalence through 2050 with Socio-demographic Index (SDI) and high BMI as predictors, respectively. FINDINGS : In 2021, there were 529 million (95% uncertainty interval [UI] 500–564) people living with diabetes worldwide, and the global age-standardised total diabetes prevalence was 6·1% (5·8–6·5). At the super-region level, the highest age-standardised rates were observed in north Africa and the Middle East (9·3% [8·7–9·9]) and, at the regional level, in Oceania (12·3% [11·5–13·0]). Nationally, Qatar had the world’s highest age-specific prevalence of diabetes, at 76·1% (73·1–79·5) in individuals aged 75–79 years. Total diabetes prevalence—especially among older adults—primarily reflects type 2 diabetes, which in 2021 accounted for 96·0% (95·1–96·8) of diabetes cases and 95·4% (94·9–95·9) of diabetes DALYs worldwide. In 2021, 52·2% (25·5–71·8) of global type 2 diabetes DALYs were attributable to high BMI. The contribution of high BMI to type 2 diabetes DALYs rose by 24·3% (18·5–30·4) worldwide between 1990 and 2021. By 2050, more than 1·31 billion (1·22–1·39) people are projected to have diabetes, with expected age-standardised total diabetes prevalence rates greater than 10% in two super-regions: 16·8% (16·1–17·6) in north Africa and the Middle East and 11·3% (10·8–11·9) in Latin America and Caribbean. By 2050, 89 (43·6%) of 204 countries and territories will have an age-standardised rate greater than 10%. INTERPRETATION : Diabetes remains a substantial public health issue. Type 2 diabetes, which makes up the bulk of diabetes cases, is largely preventable and, in some cases, potentially reversible if identified and managed early in the disease course. However, all evidence indicates that diabetes prevalence is increasing worldwide, primarily due to a rise in obesity caused by multiple factors. Preventing and controlling type 2 diabetes remains an ongoing challenge. It is essential to better understand disparities in risk factor profiles and diabetes burden across populations, to inform strategies to successfully control diabetes risk factors within the context of multiple and complex drivers.Bill & Melinda Gates Foundation.http://www.thelancet.comam2024School of Health Systems and Public Health (SHSPH)SDG-03:Good heatlh and well-bein
Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes
Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues
Multilocus genotyping of giardia duodenalis in Malaysia. Infection, genetics and evolution
Giardia duodenalis is considered the most common intestinal parasite in humans worldwide. In Malaysia, 26 many studies have been conducted on the epidemiology of giardiasis. However, there is a scarcity of 27 information on the genetic diversity and the dynamics of transmission of G. duodenalis. The present study 28 was conducted to identify G. duodenalis assemblages and sub-assemblages based on multilocus analysis 29 of the glutamate dehydrogenase (gdh), beta-giardin (bg) and triose phosphate isomerase (tpi) genes. Fae- 30 cal specimens were collected from 484 Orang Asli children with a mean age of 7 years and examined 31 using light microscopy. Specimens positive for Giardia were subjected to PCR analysis of the three genes 32
and subsequent sequencing in both directions. Sequences were edited and analysed by phylogenetic 33 analysis. G. duodenalis was detected in 17% (84 of 484) of the examined specimens. Among them, 71 were 34 successfully sequenced using at least one locus. Genotyping results showed that 30 (42%) of the isolates 35 Q2 belonged to assemblage A, 32 (45%) belonged to assemblage B, while discordant genotype results were 36 observed in 9 specimens. Mixed infections were detected in 43 specimens using a tpi-based assemblage 37 specific protocol. At the sub-assemblages level, isolates belonged to assemblage A were AII. High nucle- 38
otide variation found in isolates of assemblage B made subtyping difficult to achieve. The finding of 39 assemblage B and the anthroponotic genotype AII implicates human-to-human transmission as the most 40 possible mode of transmission among Malaysian aborigines. The high polymorphism found in isolates of 41 assemblage B warrants a more defining tool to discriminate assemblage B at the sub-assemblage level
Multi locus genotyping of Giardia duodenalis in Malaysia
Giardia duodenalis is considered the most common intestinal parasite in humans worldwide. In Malaysia, many studies have been conducted on the epidemiology of giardiasis. However, there is a scarcity of information on the genetic diversity and the dynamics of transmission of G. duodenalis. The present study was conducted to identify G. duodenalis assemblages and sub-assemblages based on multilocus analysis of the glutamate dehydrogenase (gdh), beta-giardin (bg) and triose phosphate isomerase (tpi) genes. Faecal specimens were collected from 484 Orang Asli children with a mean age of 7 years and examined using light microscopy. Specimens positive for Giardia were subjected to PCR analysis of the three genes and subsequent sequencing in both directions. Sequences were edited and analysed by phylogenetic analysis. G. duodenalis was detected in 17 (84 of 484) of the examined specimens. Among them, 71 were successfully sequenced using at least one locus. Genotyping results showed that 30 (42) of the isolates belonged to assemblage A, 32 (45) belonged to assemblage B, while discordant genotype results were observed in 9 specimens. Mixed infections were detected in 43 specimens using a tpi-based assemblage specific protocol. At the sub-assemblages level, isolates belonged to assemblage A were AII. High nucleotide variation found in isolates of assemblage B made subtyping difficult to achieve. The finding of assemblage B and the anthroponotic genotype All implicates human-to-human transmission as the most possible mode of transmission among Malaysian aborigines. The high polymorphism found in isolates of assemblage B warrants a more defining tool to discriminate assemblage B at the sub-assemblage level. (C) 2013 Elsevier B.V. All rights reserved