| 51. |
- Santosa, Ailiana, 1976-
(author)
-
Where are the world’s disease patterns heading? : The challenges of epidemiological transition
- 2015
-
Doctoral thesis (other academic/artistic)abstract
- INTRODUCTION: Epidemiological transition theory, first postulated by Omran in 1971, provides a useful framework for understanding cause-specific mortality changes and may contribute usefully to predictions about cause-specific mortality. However, understandings of mortality transitions and associated epidemiological changes remain poorly defined for public health practitioners due to lack of evidence from low- and middle-income countries. Therefore, understanding of the concept and development of epidemiological transition theory as well as population burden of premature mortality attributable to risk factors is needed.OBJECTIVES: This thesis aims to understand how epidemiological transition theory has been applied in different contexts, using available evidence on mortality transitions from high, middle- and low- income countries, as well as the contribution of risk factors to mortality transitions, particularly for premature mortality.METHODS: A Medline literature search from 1971 to 2013 was conducted to synthesise published evidence on mortality transition (paper I). A descriptive analysis of trends in cause of death using INDEPTH data was conducted, focusing on specific causes of death in 12 INDEPTH sites in Africa and Asia, using the INDEPTH 2013 standard population structure for appropriate comparisons across sites (paper II). A retrospective dynamic cohort database was constructed from Swedish population registers for the age range 30-69 years during 1991-2006, to measure reductions in premature non-communicable disease mortality using a life table method (paper III). Prospective cohort data from Västerbotten Intervention Programme from 1990 to 2006 were used to measure the magnitude of premature non-communicable disease mortality reductions associated with risk factor changes for each period of time (paper IV).FINDINGS: There were changes in emphasis in research on epidemiological transition over the four decades from 1971 to 2013, from cause of death to wide-ranging aspects of the determinants of mortality with increasing research interests in low-and middle-income countries, with some unconsidered aspects of social determinants contributing to deviations from classic theoretical pathways. Mortality rates declined in most sites, with the annual reductions in premature adult mortality varied across INDEPTH sites, Sweden, which now is at late stage of epidemiological transition stage, achieved a 25% reduction in premature mortality during 1991-2006. Overall downward trends in risk factors have helped to reduce premature mortality in the population of Västerbotten County, but some benefits were offset by other increasing risks. The largest mortality changes accrued from reductions in smoking, hypertension and hypercholesterolaemia.CONCLUSIONS: This thesis established patterns of current epidemiological transition in high, middle-and low-income countries (Asia and Africa), where the theory fits the transition patterns in some countries, but with some needs for further adjustments in other settings, as well as deviations from the classical ET theory in the last four decades. It highlights the need to identify the burden of mortality and morbidity, particularly for reducing mortality occurring before the age of 70 years and its attribution to risk factors, which are a major public health challenge. This informs shifting of public health priorities and resources towards prevention and control of chronic non-communicable disease risk factors.
|
|
| 52. |
- Siebrecht, Mathilde I., et al.
(author)
-
Magnifying the differences : Investigating variability in Dorset Paleo-Inuit organic material culture using microscopic analysis
- 2021
-
In: Bones at a Crossroads : Integrating Worked Bone Research with Archaeometry and Social Zooarchaeology - Integrating Worked Bone Research with Archaeometry and Social Zooarchaeology. - 9789464270068 - 9789464270075 - 9789464270082 ; , s. 51-72
-
Book chapter (peer-reviewed)abstract
- Arctic archaeologists generally accept that Dorset Paleo-Inuit (Tuniit) (c. 800 BC-1300 AD) toolkits exhibit high levels of typological uniformity across Arctic Canada and Greenland. This understanding implies that the artifacts were likely produced according to a standardized set of practices that were somehow ÷einforced over time and shared across the isolated sites and communities inhabiting this vast region. In contrast, recent theoretical developmentsin the study of technology highlight that material culture traditions are reproduced through localized social practices, and involve both individual and community-based decisionmaking processes, which would predict a higher level of variability in local manufacture and design features. Our aim in this pilot-study is to test whether Dorset artifacts are, in fact, produced and used in highly standardized ways. We focus on two important tool types crucial to survival in the North: needles and harpoon heads. We sampled assemblages from three Dorset sites located up to 800 km from one other and dating to different Dorset culturalperiods. Our results indicate that the sets of tools were made and used in very different ways despite their outward typological similarity. This may reflect the fact that local technological traditions were being learned and practiced differently at each site, though much more work is needed to fully understand the implications of these results in terms of social learning, cultural inheritance, and inter-regional interaction patterns.
|
|
| 53. |
- Speliotes, Elizabeth K., et al.
(author)
-
Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
- 2010
-
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 937-948
-
Journal article (peer-reviewed)abstract
- Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10−8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
|
|
| 54. |
- Thanabalasingham, Gaya, et al.
(author)
-
Mutations in HNF1A Result in Marked Alterations of Plasma Glycan Profile
- 2013
-
In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 62:4, s. 1329-1337
-
Journal article (peer-reviewed)abstract
- A recent genome-wide association study identified hepatocyte nuclear factor 1-alpha (HNF1A) as a key regulator of fucosylation. We hypothesized that loss-of-function HNF1A mutations causal for maturity-onset diabetes of the young (MOD?) would display altered fucosylation of N-linked glycans on plasma proteins and that glycan biomarkers could improve the efficiency of a diagnosis of HNF1A-MODY. In a pilot comparison of 33 subjects with HNF1A-MODY and 41 subjects with type 2 diabetes, 15 of 29 glycan measurements differed between the two groups. The DG9-glycan index, which is the ratio of fucosylated to nonfucosylated triantennary glycans, provided optimum discrimination in the pilot study and was examined further among additional subjects with HNF1A-MODY (n = 188), glucokinase (GCE)-MODY (n = 118), hepatocyte nuclear factor 4-alpha (HNF4A)-MODY (n = 40), type 1 diabetes (n = 98), type 2 diabetes (n = 167), and nondiabetic controls (n = 98). The DG9-glycan index was markedly lower in HNF1A-MODY than in controls or other diabetes subtypes, offered good discrimination between HNF1A-MODY and both type 1 and type 2 diabetes (C statistic >= 0.90), and enabled us to detect three previously undetected HNF1A mutations in patients with diabetes. In conclusion, glycan profiles are altered substantially in HNF1A-MODY, and the DG9-glycan index has potential clinical value as a diagnostic biomarker of HNF1A dysfunction.
|
|
| 55. |
-
The Seventeenth Data Release of the Sloan Digital Sky Surveys : Complete Release of MaNGA, MaStar, and APOGEE-2 Data
- 2022
-
In: Astrophysical Journal Supplement Series. - : Institute of Physics (IOP). - 0067-0049 .- 1538-4365. ; 259:2
-
Journal article (peer-reviewed)abstract
- This paper documents the seventeenth data release (DR17) from the Sloan Digital Sky Surveys; the fifth and final release from the fourth phase (SDSS-IV). DR17 contains the complete release of the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey, which reached its goal of surveying over 10,000 nearby galaxies. The complete release of the MaNGA Stellar Library accompanies this data, providing observations of almost 30,000 stars through the MaNGA instrument during bright time. DR17 also contains the complete release of the Apache Point Observatory Galactic Evolution Experiment 2 survey that publicly releases infrared spectra of over 650,000 stars. The main sample from the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), as well as the subsurvey Time Domain Spectroscopic Survey data were fully released in DR16. New single-fiber optical spectroscopy released in DR17 is from the SPectroscipic IDentification of ERosita Survey subsurvey and the eBOSS-RM program. Along with the primary data sets, DR17 includes 25 new or updated value-added catalogs. This paper concludes the release of SDSS-IV survey data. SDSS continues into its fifth phase with observations already underway for the Milky Way Mapper, Local Volume Mapper, and Black Hole Mapper surveys.
|
|
| 56. |
- Wild, Edward, et al.
(author)
-
Abnormal peripheral chemokine profile in Huntington's disease.
- 2011
-
In: PLoS Currents. - 2157-3999. ; 3
-
Journal article (peer-reviewed)abstract
- Huntington's disease (HD) is an inherited neurodegenerative disorder characterized by both neurological and systemic abnormalities. Immune activation is a well-established feature of the HD brain and we have previously demonstrated a widespread, progressive innate immune response detectable in plasma throughout the course of HD. In the present work we used multiplex ELISA to quantify levels of chemokines in plasma from controls and subjects at different stages of HD. We found an altered chemokine profile tracking with disease progression, with significant elevations of five chemokines (eotaxin-3, MIP-1β, eotaxin, MCP-1 and MCP-4) while three (eotaxin-3, MIP-1β and eotaxin) showed significant linear increases across advancing disease stages. We validated our results in a separate sample cohort including subjects at different stages of HD. Here we saw that chemokine levels (MCP-1 and eotaxin) correlated with clinical scores. We conclude that, like cytokines, chemokines may be linked to the pathogenesis of HD, and that immune molecules may be valuable in tracking and exploring the pathogenesis of HD.
|
|
| 57. |
- Wild, Edward J, et al.
(author)
-
Quantification of mutant huntingtin protein in cerebrospinal fluid from Huntington's disease patients.
- 2015
-
In: The Journal of clinical investigation. - 1558-8238. ; 125:5, s. 1979-1986
-
Journal article (peer-reviewed)abstract
- Quantification of disease-associated proteins in the cerebrospinal fluid (CSF) has been critical for the study and treatment of several neurodegenerative disorders; however, mutant huntingtin protein (mHTT), the cause of Huntington's disease (HD), is at very low levels in CSF and, to our knowledge, has never been measured previously.
|
|
| 58. |
- Willer, Cristen J., et al.
(author)
-
Discovery and refinement of loci associated with lipid levels
- 2013
-
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1274-1283
-
Journal article (peer-reviewed)abstract
- Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 x 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.
|
|
