| 1. |
- Driscoll, T, et al.
(författare)
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Global and regional burden of disease and injury in 2016 arising from occupational exposures: a systematic analysis for the Global Burden of Disease Study 2016
- 2020
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Ingår i: Occupational and environmental medicine. - : BMJ. - 1470-7926 .- 1351-0711. ; 77:3, s. 133-141
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Tidskriftsartikel (refereegranskat)abstract
- This study provides an overview of the influence of occupational risk factors on the global burden of disease as estimated by the occupational component of the Global Burden of Disease (GBD) 2016 study.MethodsThe GBD 2016 study estimated the burden in terms of deaths and disability-adjusted life years (DALYs) arising from the effects of occupational risk factors (carcinogens; asthmagens; particulate matter, gases and fumes (PMGF); secondhand smoke (SHS); noise; ergonomic risk factors for low back pain; risk factors for injury). A population attributable fraction (PAF) approach was used for most risk factors.ResultsIn 2016, globally, an estimated 1.53 (95% uncertainty interval 1.39–1.68) million deaths and 76.1 (66.3–86.3) million DALYs were attributable to the included occupational risk factors, accounting for 2.8% of deaths and 3.2% of DALYs from all causes. Most deaths were attributable to PMGF, carcinogens (particularly asbestos), injury risk factors and SHS. Most DALYs were attributable to injury risk factors and ergonomic exposures. Men and persons 55 years or older were most affected. PAFs ranged from 26.8% for low back pain from ergonomic risk factors and 19.6% for hearing loss from noise to 3.4% for carcinogens. DALYs per capita were highest in Oceania, Southeast Asia and Central sub-Saharan Africa. On a per capita basis, between 1990 and 2016 there was an overall decrease of about 31% in deaths and 25% in DALYs.ConclusionsOccupational exposures continue to cause an important health burden worldwide, justifying the need for ongoing prevention and control initiatives.
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| 2. |
- Sloot, Frea, et al.
(författare)
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Inventory of current EU paediatric vision and hearing screening programmes
- 2015
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Ingår i: Journal of Medical Screening. - : SAGE Publications. - 0969-1413 .- 1475-5793. ; 22:2, s. 55-64
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To examine the diversity in paediatric vision and hearing screening programmes in Europe. Methods: Themes for comparison of screening programmes derived from literature were used to compile three questionnaires on vision, hearing, and public health screening. Tests used, professions involved, age, and frequency of testing seem to influence sensitivity, specificity, and costs most. Questionnaires were sent to ophthalmologists, orthoptists, otolaryngologists, and audiologists involved in paediatric screening in all EU full-member, candidate, and associate states. Answers were cross-checked. Results: Thirty-nine countries participated; 35 have a vision screening programme, 33 a nation-wide neonatal hearing screening programme. Visual acuity (VA) is measured in 35 countries, in 71% of these more than once. First measurement of VA varies from three to seven years of age, but is usually before age five. At age three and four, picture charts, including Lea Hyvarinen, are used most; in children over four, Tumbling-E and Snellen. As first hearing screening test, otoacoustic emission is used most in healthy neonates, and auditory brainstem response in premature newborns. The majority of hearing testing programmes are staged; children are referred after 1–4 abnormal tests. Vision screening is performed mostly by paediatricians, ophthalmologists, or nurses. Funding is mostly by health insurance or state. Coverage was reported as >95% in half of countries, but reporting was often not first-hand. Conclusion: Largest differences were found in VA charts used (12), professions involved in vision screening (10), number of hearing screening tests before referral (1–4), and funding sources (8).
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| 3. |
- Spadafora, E., De Ros, L.F., Zuffa, G.G., Morad, S. and Al-Aasm, I.S.
(författare)
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Diagenetic evolution of hybrid and lithic synorogenic arenites (Miocene), northern Apennines, Italy
- 1998
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Ingår i: Morad, S. (ed), Carbonate Cementation of Sandstones (International Association of Sedimentologists, IAS, Special Publication, 26). ; , s. 241-260
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Tidskriftsartikel (refereegranskat)
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| 4. |
- Concepcion Gil-Rodriguez, Maria, et al.
(författare)
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De Novo Heterozygous Mutations in SMC3 Cause a Range of Cornelia de Lange Syndrome-Overlapping Phenotypes
- 2015
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Ingår i: Human Mutation. - : Wiley: 12 months. - 1059-7794 .- 1098-1004. ; 36:4, s. 454-462
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Tidskriftsartikel (refereegranskat)abstract
- Cornelia de Lange syndrome (CdLS) is characterized by facial dysmorphism, growth failure, intellectual disability, limb malformations, and multiple organ involvement. Mutations in five genes, encoding subunits of the cohesin complex (SMC1A, SMC3, RAD21) and its regulators (NIPBL, HDAC8), account for at least 70% of patients with CdLS or CdLS-like phenotypes. To date, only the clinical features from a single CdLS patient with SMC3 mutation has been published. Here, we report the efforts of an international research and clinical collaboration to provide clinical comparison of 16 patients with CdLS-like features caused by mutations in SMC3. Modeling of the mutation effects on protein structure suggests a dominant-negative effect on the multimeric cohesin complex. When compared with typical CdLS, many SMC3-associated phenotypes are also characterized by postnatal microcephaly but with a less distinctive craniofacial appearance, a milder prenatal growth retardation that worsens in childhood, few congenital heart defects, and an absence of limb deficiencies. While most mutations are unique, two unrelated affected individuals shared the same mutation but presented with different phenotypes. This work confirms that de novo SMC3 mutations account for approximate to 1%-2% of CdLS-like phenotypes.
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| 5. |
- GBD 2021 Risk Factors Collaborators,, et al.
(författare)
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Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021.
- 2024
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Ingår i: Lancet (London, England). - 1474-547X .- 0140-6736. ; 403:10440, s. 2162-2203
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021.The GBD 2021 risk factor analysis used data from 54561 total distinct sources to produce epidemiological estimates for 88 risk factors and their associated health outcomes for a total of 631 risk-outcome pairs. Pairs were included on the basis of data-driven determination of a risk-outcome association. Age-sex-location-year-specific estimates were generated at global, regional, and national levels. Our approach followed the comparative risk assessment framework predicated on a causal web of hierarchically organised, potentially combinative, modifiable risks. Relative risks (RRs) of a given outcome occurring as a function of risk factor exposure were estimated separately for each risk-outcome pair, and summary exposure values (SEVs), representing risk-weighted exposure prevalence, and theoretical minimum risk exposure levels (TMRELs) were estimated for each risk factor. These estimates were used to calculate the population attributable fraction (PAF; ie, the proportional change in health risk that would occur if exposure to a risk factor were reduced to the TMREL). The product of PAFs and disease burden associated with a given outcome, measured in disability-adjusted life-years (DALYs), yielded measures of attributable burden (ie, the proportion of total disease burden attributable to a particular risk factor or combination of risk factors). Adjustments for mediation were applied to account for relationships involving risk factors that act indirectly on outcomes via intermediate risks. Attributable burden estimates were stratified by Socio-demographic Index (SDI) quintile and presented as counts, age-standardised rates, and rankings. To complement estimates of RR and attributable burden, newly developed burden of proof risk function (BPRF) methods were applied to yield supplementary, conservative interpretations of risk-outcome associations based on the consistency of underlying evidence, accounting for unexplained heterogeneity between input data from different studies. Estimates reported represent the mean value across 500 draws from the estimate's distribution, with 95% uncertainty intervals (UIs) calculated as the 2·5th and 97·5th percentile values across the draws.Among the specific risk factors analysed for this study, particulate matter air pollution was the leading contributor to the global disease burden in 2021, contributing 8·0% (95% UI 6·7-9·4) of total DALYs, followed by high systolic blood pressure (SBP; 7·8% [6·4-9·2]), smoking (5·7% [4·7-6·8]), low birthweight and short gestation (5·6% [4·8-6·3]), and high fasting plasma glucose (FPG; 5·4% [4·8-6·0]). For younger demographics (ie, those aged 0-4 years and 5-14 years), risks such as low birthweight and short gestation and unsafe water, sanitation, and handwashing (WaSH) were among the leading risk factors, while for older age groups, metabolic risks such as high SBP, high body-mass index (BMI), high FPG, and high LDL cholesterol had a greater impact. From 2000 to 2021, there was an observable shift in global health challenges, marked by a decline in the number of all-age DALYs broadly attributable to behavioural risks (decrease of 20·7% [13·9-27·7]) and environmental and occupational risks (decrease of 22·0% [15·5-28·8]), coupled with a 49·4% (42·3-56·9) increase in DALYs attributable to metabolic risks, all reflecting ageing populations and changing lifestyles on a global scale. Age-standardised global DALY rates attributable to high BMI and high FPG rose considerably (15·7% [9·9-21·7] for high BMI and 7·9% [3·3-12·9] for high FPG) over this period, with exposure to these risks increasing annually at rates of 1·8% (1·6-1·9) for high BMI and 1·3% (1·1-1·5) for high FPG. By contrast, the global risk-attributable burden and exposure to many other risk factors declined, notably for risks such as child growth failure and unsafe water source, with age-standardised attributable DALYs decreasing by 71·5% (64·4-78·8) for child growth failure and 66·3% (60·2-72·0) for unsafe water source. We separated risk factors into three groups according to trajectory over time: those with a decreasing attributable burden, due largely to declining risk exposure (eg, diet high in trans-fat and household air pollution) but also to proportionally smaller child and youth populations (eg, child and maternal malnutrition); those for which the burden increased moderately in spite of declining risk exposure, due largely to population ageing (eg, smoking); and those for which the burden increased considerably due to both increasing risk exposure and population ageing (eg, ambient particulate matter air pollution, high BMI, high FPG, and high SBP).Substantial progress has been made in reducing the global disease burden attributable to a range of risk factors, particularly those related to maternal and child health, WaSH, and household air pollution. Maintaining efforts to minimise the impact of these risk factors, especially in low SDI locations, is necessary to sustain progress. Successes in moderating the smoking-related burden by reducing risk exposure highlight the need to advance policies that reduce exposure to other leading risk factors such as ambient particulate matter air pollution and high SBP. Troubling increases in high FPG, high BMI, and other risk factors related to obesity and metabolic syndrome indicate an urgent need to identify and implement interventions.Bill & Melinda Gates Foundation.
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| 6. |
- Wei, Yong, et al.
(författare)
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The MYC oncoprotein directly interacts with its chromatin cofactor PNUTS to recruit PP1 phosphatase
- 2022
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Ingår i: Nucleic Acids Research. - Oxford, United Kingdom : Oxford University Press. - 0305-1048 .- 1362-4962. ; 50:6, s. 3505-3522
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Tidskriftsartikel (refereegranskat)abstract
- Despite MYC dysregulation in most human cancers, strategies to target this potent oncogenic driver remain an urgent unmet need. Recent evidence shows the PP1 phosphatase and its regulatory subunit PNUTS control MYC phosphorylation, chromatin occupancy, and stability, however the molecular basis remains unclear. Here we demonstrate that MYC interacts directly with PNUTS through the MYC homology Box 0 (MB0), a highly conserved region recently shown to be important for MYC oncogenic activity. By NMR we identified a distinct peptide motif within MB0 that interacts with PNUTS residues 1-148, a functional unit, here termed PNUTS amino-terminal domain (PAD). Using NMR spectroscopy we determined the solution structure of PAD, and characterised its MYC-binding patch. Point mutations of residues at the MYC-PNUTS interface significantly weaken their interaction both in vitro and in vivo, leading to elevated MYC phosphorylation. These data demonstrate that the MB0 region of MYC directly interacts with the PAD of PNUTS, which provides new insight into the control mechanisms of MYC as a regulator of gene transcription and a pervasive cancer driver.
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