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Sökning: WFRF:(Sayed M) > (2010-2014)

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1.
  • Walters, R G, et al. (författare)
  • A new highly penetrant form of obesity due to deletions on chromosome 16p11.2.
  • 2010
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 463:7281, s. 671-5
  • Tidskriftsartikel (refereegranskat)abstract
    • Obesity has become a major worldwide challenge to public health, owing to an interaction between the Western 'obesogenic' environment and a strong genetic contribution. Recent extensive genome-wide association studies (GWASs) have identified numerous single nucleotide polymorphisms associated with obesity, but these loci together account for only a small fraction of the known heritable component. Thus, the 'common disease, common variant' hypothesis is increasingly coming under challenge. Here we report a highly penetrant form of obesity, initially observed in 31 subjects who were heterozygous for deletions of at least 593 kilobases at 16p11.2 and whose ascertainment included cognitive deficits. Nineteen similar deletions were identified from GWAS data in 16,053 individuals from eight European cohorts. These deletions were absent from healthy non-obese controls and accounted for 0.7% of our morbid obesity cases (body mass index (BMI) >or= 40 kg m(-2) or BMI standard deviation score >or= 4; P = 6.4 x 10(-8), odds ratio 43.0), demonstrating the potential importance in common disease of rare variants with strong effects. This highlights a promising strategy for identifying missing heritability in obesity and other complex traits: cohorts with extreme phenotypes are likely to be enriched for rare variants, thereby improving power for their discovery. Subsequent analysis of the loci so identified may well reveal additional rare variants that further contribute to the missing heritability, as recently reported for SIM1 (ref. 3). The most productive approach may therefore be to combine the 'power of the extreme' in small, well-phenotyped cohorts, with targeted follow-up in case-control and population cohorts.
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2.
  • Bruggmann, P., et al. (författare)
  • Historical epidemiology of hepatitis C virus (HCV) in selected countries
  • 2014
  • Ingår i: Journal of Viral Hepatitis. - Hoboken : Wiley-Blackwell. - 1352-0504 .- 1365-2893. ; 21, s. 5-33
  • Tidskriftsartikel (refereegranskat)abstract
    • Chronic infection with hepatitis C virus (HCV) is a leading indicator for liver disease. New treatment options are becoming available, and there is a need to characterize the epidemiology and disease burden of HCV. Data for prevalence, viremia, genotype, diagnosis and treatment were obtained through literature searches and expert consensus for 16 countries. For some countries, data from centralized registries were used to estimate diagnosis and treatment rates. Data for the number of liver transplants and the proportion attributable to HCV were obtained from centralized databases. Viremic prevalence estimates varied widely between countries, ranging from 0.3% in Austria, England and Germany to 8.5% in Egypt. The largest viremic populations were in Egypt, with 6358000 cases in 2008 and Brazil with 2106000 cases in 2007. The age distribution of cases differed between countries. In most countries, prevalence rates were higher among males, reflecting higher rates of injection drug use. Diagnosis, treatment and transplant levels also differed considerably between countries. Reliable estimates characterizing HCV-infected populations are critical for addressing HCV-related morbidity and mortality. There is a need to quantify the burden of chronic HCV infection at the national level.
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3.
  • Razavi, H., et al. (författare)
  • The present and future disease burden of hepatitis C virus (HCV) infection with today's treatment paradigm
  • 2014
  • Ingår i: Journal of Viral Hepatitis. - Hoboken : Wiley-Blackwell. - 1352-0504 .- 1365-2893. ; 21:Suppl. 1, s. 34-59
  • Tidskriftsartikel (refereegranskat)abstract
    • The disease burden of hepatitis C virus (HCV) is expected to increase as the infected population ages. A modelling approach was used to estimate the total number of viremic infections, diagnosed, treated and new infections in 2013. In addition, the model was used to estimate the change in the total number of HCV infections, the disease progression and mortality in 2013-2030. Finally, expert panel consensus was used to capture current treatment practices in each country. Using today's treatment paradigm, the total number of HCV infections is projected to decline or remain flat in all countries studied. However, in the same time period, the number of individuals with late-stage liver disease is projected to increase. This study concluded that the current treatment rate and efficacy are not sufficient to manage the disease burden of HCV. Thus, alternative strategies are required to keep the number of HCV individuals with advanced liver disease and liver-related deaths from increasing.
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4.
  • Wedemeyer, H., et al. (författare)
  • Strategies to manage hepatitis C virus (HCV) disease burden
  • 2014
  • Ingår i: Journal of Viral Hepatitis. - Hoboken : Wiley-Blackwell. - 1352-0504 .- 1365-2893. ; 21, s. 60-89
  • Tidskriftsartikel (refereegranskat)abstract
    • The number of hepatitis C virus (HCV) infections is projected to decline while those with advanced liver disease will increase. A modeling approach was used to forecast two treatment scenarios: (i) the impact of increased treatment efficacy while keeping the number of treated patients constant and (ii) increasing efficacy and treatment rate. This analysis suggests that successful diagnosis and treatment of a small proportion of patients can contribute significantly to the reduction of disease burden in the countries studied. The largest reduction in HCV-related morbidity and mortality occurs when increased treatment is combined with higher efficacy therapies, generally in combination with increased diagnosis. With a treatment rate of approximately 10%, this analysis suggests it is possible to achieve elimination of HCV (defined as a >90% decline in total infections by 2030). However, for most countries presented, this will require a 3-5 fold increase in diagnosis and/or treatment. Thus, building the public health and clinical provider capacity for improved diagnosis and treatment will be critical.
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5.
  • Falchi, M., et al. (författare)
  • Low copy number of the salivary amylase gene predisposes to obesity
  • 2014
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 46:5, s. 492-497
  • Tidskriftsartikel (refereegranskat)abstract
    • Common multi-allelic copy number variants (CNVs) appear enriched for phenotypic associations compared to their biallelic counterparts. Here we investigated the influence of gene dosage effects on adiposity through a CNV association study of gene expression levels in adipose tissue. We identified significant association of a multi-allelic CNV encompassing the salivary amylase gene (AMY1) with body mass index (BMI) and obesity, and we replicated this finding in 6,200 subjects. Increased AMY1 copy number was positively associated with both amylase gene expression (P = 2.31 × 10-14) and serum enzyme levels (P < 2.20 × 10-16), whereas reduced AMY1 copy number was associated with increased BMI (change in BMI per estimated copy =-0.15 (0.02) kg/m 2; P = 6.93 × 10-10) and obesity risk (odds ratio (OR) per estimated copy = 1.19, 95% confidence interval (CI) = 1.13-1.26; P = 1.46 × 10-10). The OR value of 1.19 per copy of AMY1 translates into about an eightfold difference in risk of obesity between subjects in the top (copy number > 9) and bottom (copy number < 4) 10% of the copy number distribution. Our study provides a first genetic link between carbohydrate metabolism and BMI and demonstrates the power of integrated genomic approaches beyond genome-wide association studies. © 2014 Nature America, Inc. All rights reserved.
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6.
  • Wang, Haidong, et al. (författare)
  • Global, regional, and national levels of neonatal, infant, and under-5 mortality during 1990-2013 : a systematic analysis for the Global Burden of Disease Study 2013
  • 2014
  • Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 384:9947, s. 957-979
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Remarkable financial and political efforts have been focused on the reduction of child mortality during the past few decades. Timely measurements of levels and trends in under-5 mortality are important to assess progress towards the Millennium Development Goal 4 (MDG 4) target of reduction of child mortality by two thirds from 1990 to 2015, and to identify models of success.METHODS: We generated updated estimates of child mortality in early neonatal (age 0-6 days), late neonatal (7-28 days), postneonatal (29-364 days), childhood (1-4 years), and under-5 (0-4 years) age groups for 188 countries from 1970 to 2013, with more than 29 000 survey, census, vital registration, and sample registration datapoints. We used Gaussian process regression with adjustments for bias and non-sampling error to synthesise the data for under-5 mortality for each country, and a separate model to estimate mortality for more detailed age groups. We used explanatory mixed effects regression models to assess the association between under-5 mortality and income per person, maternal education, HIV child death rates, secular shifts, and other factors. To quantify the contribution of these different factors and birth numbers to the change in numbers of deaths in under-5 age groups from 1990 to 2013, we used Shapley decomposition. We used estimated rates of change between 2000 and 2013 to construct under-5 mortality rate scenarios out to 2030.FINDINGS: We estimated that 6·3 million (95% UI 6·0-6·6) children under-5 died in 2013, a 64% reduction from 17·6 million (17·1-18·1) in 1970. In 2013, child mortality rates ranged from 152·5 per 1000 livebirths (130·6-177·4) in Guinea-Bissau to 2·3 (1·8-2·9) per 1000 in Singapore. The annualised rates of change from 1990 to 2013 ranged from -6·8% to 0·1%. 99 of 188 countries, including 43 of 48 countries in sub-Saharan Africa, had faster decreases in child mortality during 2000-13 than during 1990-2000. In 2013, neonatal deaths accounted for 41·6% of under-5 deaths compared with 37·4% in 1990. Compared with 1990, in 2013, rising numbers of births, especially in sub-Saharan Africa, led to 1·4 million more child deaths, and rising income per person and maternal education led to 0·9 million and 2·2 million fewer deaths, respectively. Changes in secular trends led to 4·2 million fewer deaths. Unexplained factors accounted for only -1% of the change in child deaths. In 30 developing countries, decreases since 2000 have been faster than predicted attributable to income, education, and secular shift alone.INTERPRETATION: Only 27 developing countries are expected to achieve MDG 4. Decreases since 2000 in under-5 mortality rates are accelerating in many developing countries, especially in sub-Saharan Africa. The Millennium Declaration and increased development assistance for health might have been a factor in faster decreases in some developing countries. Without further accelerated progress, many countries in west and central Africa will still have high levels of under-5 mortality in 2030.
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8.
  • Unelius, C. Rikard, et al. (författare)
  • Volatiles from green-lipped mussel as a lead to vespid wasp attractants
  • 2014
  • Ingår i: Journal of applied entomology. - : Wiley. - 0931-2048 .- 1439-0418. ; 138:1-2, s. 87-95
  • Tidskriftsartikel (refereegranskat)abstract
    • Vespid wasps (Vespula vulgaris L. and V.germanica Fab. Hymenoptera; Vespidae) are highly abundant in 1 million ha of New Zealand's indigenous beech forests (Nothofagus spp.) and have had detrimental effects on the New Zealand native fauna. This hyperabundance is due in part to the vast supply of carbohydrate-rich honeydew produced by scale insects Ultracoelostoma spp. native to New Zealand. Current control methods include the use of wet cat food as a protein source with insecticide as a lure-and-kill-based system, but there are problems with fresh baits degrading rapidly, and a more durable formulation would enable the expansion and longevity of wasp control. Four crude protein baits were tested for vespid attraction. Green-lipped mussels had the highest vespid catch of the crude baits tested, and aged and fresh mussels were equally attractive. From headspace analysis of the green-lipped mussel volatiles, a series of butanoate esters, 3-octanone and 1-octen-3-ol were identified as possible attractants. These compounds were tested individually and in various blend combinations for the attraction of Vespula wasps in matagouri vegetation at the edge of beech forests. We found synergistic effects between single attractive compounds when tested in various combinations, and the multicomponent lures were more attractive to these wasps than heptyl and octyl butanoate, previously identified attractants for vespid species. The new multicomponent lures could form the basis for a new generation of attractants for social wasps that can provide sustained control methods for invasive vespid wasps.
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9.
  • Brown, Robert L., et al. (författare)
  • Attraction of the invasive social wasp, Vespula vulgaris, by volatiles from fermented brown sugar
  • 2014
  • Ingår i: Entomologia Experimentalis et Applicata. - : Wiley. - 0013-8703 .- 1570-7458. ; 151:2, s. 182-190
  • Tidskriftsartikel (refereegranskat)abstract
    • The introduction of invasive social wasp species of the genus Vespula (Hymenoptera: Vespidae) to New Zealand has caused a major ecological problem, particularly in the beech forests (Nothofagus spp.) of the South Island, where they have destabilized the native bird and invertebrate biodiversity. New attractants are under investigation as part of a search for pest management solutions. Fermenting brown sugar has been previously reported as a social wasp attractant. This work was undertaken to identify compounds from fermented brown sugar attractive to social wasps. Raw fermented brown sugar was confirmed to be attractive in a field trial and 10 chemical compounds present in the headspace were positively identified by coupled gas chromatography-mass spectrometry and synthetic references. During electroantennogram experiments, 3-methyl-1-butanol, 3-methylbutyl acetate, and ethyl hexanoate elicited high electrophysiological responses from Vespula vulgaris (L.) antennae. These compounds mediated attraction of V.vulgaris wasps in forest margins by trapping. A blend of these compounds could be used as a lure in a monitoring tool, or even a local suppression method if combined with a toxin.
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10.
  • el-Din, Sayed H. Seif, et al. (författare)
  • Potential effect of the medicinal plants Calotropis procera, Ficus elastica and Zingiber officinale against Schistosoma mansoni in mice
  • 2014
  • Ingår i: Pharmaceutical Biology. - : Informa UK Limited. - 1744-5116 .- 1388-0209. ; 52:2, s. 144-150
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Calotropis procera (Ait.) R. Br. (Asclepiadaceae), Ficus elastica Roxb. (Moraceae) and Zingiber officinale Roscoe (Zingiberaceae) have been traditionally used to treat many diseases. Objective: The antischistosomal activity of these plant extracts was evaluated against Schistosoma mansoni. Materials and methods: Male mice exposed to 80 +/- 10 cercariae per mouse were divided into two batches. The first was divided into five groups: (I) infected untreated, while groups from (II-V) were treated orally (500 mg/kg for three consecutive days) by aqueous stem latex and flowers of C. procera, latex of F. elastica and ether extract of Z. officinale, respectively. The second batch was divided into four comparable groups (except Z. officinale-treated group) similarly treated as the first batch in addition to the antacid ranitidine (30 mg/kg) 1 h before extract administration. Safety, worm recovery, tissues egg load and oogram pattern were assessed. Results: Calotropis procera latex and flower extracts are toxic (50-70% mortality) even in a small dose (250 mg/kg) before washing off their toxic rubber. Zingiber officinale extract insignificantly decrease (7.26%) S. mansoni worms. When toxic rubber was washed off and ranitidine was used, C. procera (stem latex and flowers) and F. elastica extracts revealed significant S. mansoni worm reductions by 45.31, 53.7 and 16.71%, respectively. Moreover, C. procera extracts produced significant reductions in tissue egg load (similar to 34-38.5%) and positively affected oogram pattern. Conclusion: The present study may be useful to supplement information with regard to C. procera and F. elastica antischistosomal activity and provide a basis for further experimental trials.
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