Message Flow Control

High level communication by means of the exchange of messages between different organizations or organizational units is studied. The concepts of business transaction and business transaction protocol are discussed. Message exchanges are controlled by a message handler that enforces a transaction protocol. The design and implementation of a generic message handler is described. The design is independent of a specific application. It offers a flexible implementation of protocols: dedicated subprocesses handle each message type. Changes in a protocol can easily be accommodated by adapting the subprocesses. A prototype has been written in the executable specification language ExSpect. The protocols can be validated by simulating the message exchange for a number of cases. As an application of the prototype, a party in a logistic chain using EDI is described

Lack of association of two common polymorphisms on 9p21 with risk of coronary heart disease and myocardial infarction; results from a prospective cohort study

Background: Recent genome wide association (GWA) studies identified two Single Nucleotide Polymorphisms (SNP) (rs10757278 and rs10757274) in the region of the CDK2NA and CDK2NB genes to be consistently associated with the risks of coronary heart disease (CHD) and myocardial infarction (MI). We examined the SNPs in relation to the risk of CHD and MI in a large population based study of elderly population. Methods: The Rotterdam Study is a population-based, prospective cohort study among 7983 participants aged 55 years and older. Associations of the polymorphisms with CHD and MI were assessed by use of Cox proportional hazards analyses. Results: In an additive model, the age and sex adjusted hazard ratios (HRs) (95% confidence interval) for CHD and MI were 1.03 (0.90, 1.18) and 0.94 (0.82, 1.08) per copy of the G allele of rs10757274. The corresponding HRs were 1.03 (0.90, 1.18) and 0.93 (0.81, 1.06) for the G allele of rs10757278. The association of the SNPs with CHD and MI was not significant in any of the subgroups of CHD risk factors. Conclusion: We were not able to show an association of the studied SNPs with risks of CHD and MI. This may be due to differences in genes involved in the occurrence of CHD in young and older people

Heart failure and the risk of stroke: the Rotterdam Study

Patients with heart failure used to have an increased risk of stroke, but this may have changed with current treatment regimens. We assessed the association between heart failure and the risk of stroke in a population-based cohort that was followed since 1990. The study uses the cohort of the Rotterdam Study and is based on 7,546 participants who at baseline (1990–1993) were aged 55 years or over and free from stroke. The associations between heart failure and risk of stroke were assessed using time-dependent Cox proportional hazards models, adjusted for cardiovascular risk factors (smoking, diabetes mellitus, BMI, ankle brachial index, blood pressure, atrial fibrillation, myocardial infarction and relevant medication). At baseline, 233 participants had heart failure. During an average follow-up time of 9.7 years, 1,014 persons developed heart failure, and 827 strokes (470 ischemic, 75 hemorrhagic, 282 unclassified) occurred. The risk of ischemic stroke was more than five-fold increased in the first month after diagnosis of heart failure (age and sex adjusted HR 5.79, 95% CI 2.15–15.62), but attenuated over time (age and sex adjusted HR 3.50 [95% CI 1.96–6.25] after 1–6 months and 0.83 [95% CI 0.53–1.29] after 0.5–6 years). Additional adjustment for cardiovascular risk factors only marginally attenuated these risks. In conclusion, the risk of ischemic stroke is strongly increased shortly after the diagnosis of heart failure but returns to normal within 6 months after onset of heart failure

Eight common genetic variants associated with serum dheas levels suggest a key role in ageing mechanisms

Dehydroepiandrosterone sulphate (DHEAS) is the most abundant circulating steroid secreted by adrenal glands-yet its function is unknown. Its serum concentration declines significantly with increasing age, which has led to speculation that a relative DHEAS deficiency may contribute to the development of common age-related diseases or diminished longevity. We conducted a meta-analysis of genome-wide association data with 14,846 individuals and identified eight independent common SNPs associated with serum DHEAS concentrations. Genes at or near the identified loci include ZKSCAN5 (rs11761528; p = 3.15×10-36), SULT2A1 (rs2637125; p = 2.61×10-19), ARPC1A (rs740160; p = 1.56×10-16), TRIM4 (rs17277546; p = 4.50×10-11), BMF (rs7181230; p = 5.44×10-11), HHEX (rs2497306; p = 4.64×10-9), BCL2L11 (rs6738028; p = 1.72×10-8), and CYP2C9 (rs2185570; p = 2.29×10-8). These genes are associated with type 2 diabetes, lymphoma, actin filament assembly, drug and xenobiotic metabolism, and zinc finger proteins. Several SNPs were associated with changes in gene expression levels, and the related genes are connected to biological pathways linking DHEAS with ageing. This study provides much needed insight into the function of DHEAS

Lithic technological responses to Late Pleistocene glacial cycling at Pinnacle Point Site 5-6, South Africa

There are multiple hypotheses for human responses to glacial cycling in the Late Pleistocene, including changes in population size, interconnectedness, and mobility. Lithic technological analysis informs us of human responses to environmental change because lithic assemblage characteristics are a reflection of raw material transport, reduction, and discard behaviors that depend on hunter-gatherer social and economic decisions. Pinnacle Point Site 5-6 (PP5-6), Western Cape, South Africa is an ideal locality for examining the influence of glacial cycling on early modern human behaviors because it preserves a long sequence spanning marine isotope stages (MIS) 5, 4, and 3 and is associated with robust records of paleoenvironmental change. The analysis presented here addresses the question, what, if any, lithic assemblage traits at PP5-6 represent changing behavioral responses to the MIS 5-4-3 interglacial-glacial cycle? It statistically evaluates changes in 93 traits with no a priori assumptions about which traits may significantly associate with MIS. In contrast to other studies that claim that there is little relationship between broad-scale patterns of climate change and lithic technology, we identified the following characteristics that are associated with MIS 4: increased use of quartz, increased evidence for outcrop sources of quartzite and silcrete, increased evidence for earlier stages of reduction in silcrete, evidence for increased flaking efficiency in all raw material types, and changes in tool types and function for silcrete. Based on these results, we suggest that foragers responded to MIS 4 glacial environmental conditions at PP5-6 with increased population or group sizes, 'place provisioning', longer and/or more intense site occupations, and decreased residential mobility. Several other traits, including silcrete frequency, do not exhibit an association with MIS. Backed pieces, once they appear in the PP5-6 record during MIS 4, persist through MIS 3. Changing paleoenvironments explain some, but not all temporal technological variability at PP5-6.Social Science and Humanities Research Council of Canada; NORAM; American-Scandinavian Foundation; Fundacao para a Ciencia e Tecnologia [SFRH/BPD/73598/2010]; IGERT [DGE 0801634]; Hyde Family Foundations; Institute of Human Origins; National Science Foundation [BCS-9912465, BCS-0130713, BCS-0524087, BCS-1138073]; John Templeton Foundation to the Institute of Human Origins at Arizona State Universit

Association of an APOC3 promoter variant with type 2 diabetes risk and need for insulin treatment in lean persons

Aims/hypothesis: An APOC3 promoter haplotype has been previously associated with type 1 diabetes. In this population-based study, we investigated whether APOC3 polymorphisms increase type 2 diabetes risk and need for insulin treatment in lean participants. Methods: In the Rotterdam Study, a population-based prospective cohort (n = 7,983), Cox and logistic regression models were used to analyse the associations and interactive effects of APOC3 promoter variants (-482C > T, -455T > C) and BMI on type 2 diabetes risk and insulin treatment. Analyses were followed by replication in an independent case-control sample (1,817 cases, 2,292 controls) and meta-analysis. Results: In lean participants, the -482T allele was associated with increased risk of prevalent and incident type 2 diabetes: OR -482CT 1.47 (95% CI 1.13-1.92), -482TT 1.40 (95% CI 0.83-2.35), p = 0.009 for trend; HR -482CT 1.35 (95% CI 0.96-1.89), -482TT 1.68 (95% CI 0.91-3.1), p = 0.03 for trend, respectively. These results were confirmed by replication. Meta-analysis was highly significant (-482T meta-analysis p = 1.1 × 10-4). A borderline significant interaction was observed for insulin use among participants with type 2 diabetes (-482CT*BMI p = 0.06, -455TC*BMI p = 0.02). Conclusions/interpretation: At a population-based level, the influence of APOC3 promoter variants on type 2 diabetes risk varies with the level of adiposity. Lean carriers of the -482T allele had increased type 2 diabetes risk, while such an effect was not observed in overweight participants. Conversely, in overweight participants the -455C allele seemed protective against type 2 diabetes. The interaction of the variants with need for insulin treatment may indicate beta cell involvement in lean participants. Our findings suggest overlap in the genetic backgrounds of type 1 diabetes and type 2 diabetes in lean patients

Оценка фискальной иллюзии при налогообложении доходов физических лиц

Фискальная иллюзия сама по себе не является негативным явлением, она всего лишь следствие осуществляемой фискальной политики государства. Тем не менее, фискальная иллюзия нарушает представление экономических агентов о масштабах государственного влияния в перераспределении своих доходов и тем самым способствует принятию ими не самых эффективных экономических решений.Фіскальна ілюзія сама по собі не є негативним явищем, вона всього лише слідство здійснюваної фіскальної політики держави. Проте, фіскальна ілюзія порушує уявлення економічних агентів про масштаби державного впливу в перерозподілі своїх доходів і тим самим сприяє ухваленню ними не найефективніших економічних рішень

Early respiratory morbidity in a multicultural birth cohort: the Generation R Study

Ethnic disparities in the prevalence of asthma symptoms in children have been described. We evaluated to what extent the association between ethnic background and respiratory symptoms during the first 2 years of life could be explained by the mediating effect of risk factors for respiratory morbidity. The Generation R Study is a multiethnic, population-based birth cohort study. Pre and postnatal risk factors for respiratory morbidity were prospectively assessed by questionnaires. Information about ethnicity was available for 5,684 infants. The associations between ethnic background and lower respiratory symptoms at 12 and 24 months were evaluated with log-binomial regression models. Relative risks and 95 % confidence intervals (RR [95 % CI]) were computed for Cape Verdean, Moroccan, Antillean, Surinamese and Turkish ethnicity with Dutch ethnicity as the reference category. We found an increased risk of lower respiratory symptoms at 24 months in Antillean infants (1.32 [95 % CI 1.12–1.57]) that was mediated by early postnatal exposures (pets keeping, siblings, breastfeeding, daycare attendance, smoke exposure). Turkish infants also had an increased risk of lower respiratory symptoms at 12 and 24 months (1.14 [95 % CI 1.02–1.27] and 1.21 [95 % CI 1.07–1.38], respectively), partly explained by previous morbidity (eczema, infections and upper respiratory symptoms). There were no differences for Cape Verdean, Moroccan or Surinamese, as compared to Dutch infants. Hence, ethnic background was associated with respiratory symptoms during the first 2 years of life and this association was largely explained by mediating effects of known pre and postnatal risk factors for respiratory morbidity