Cardiovascular Disease Risk Factors in Older People with Intellectual Disabilities

__Abstract__ Chapter 1 General introduction There is an increasing group of older people with intellectual disability in The Netherlands, reaching almost the same life expectancy as the general population. Age-related diseases, such as cardiovascular disease, cancer and dementia are now the most encountered diseases and causes of death in older people with intellectual disabilities. Although cardiovascular disease is a major risk for older people with intellectual disabilities, no reliable information was available on cardiovascular disease risk factors, nor attention for prevention of cardiovascular disease was present prior to the start of the Healthy Ageing and Intellectual Disability (HA-ID) study. The HA-ID study aimed at gaining knowledge on healthy ageing by studying health and health risks in an older population of people with intellectual disabilities. Three large care organizations and two university departments participated in this study. Subthemes in the HA-ID study were: (1) Physical activity and fitness, (2) Nutrition and nutritional state, and (3) Mood and anxiety. By studying these themes and the interrelationships, a comprehensive concept of health and health-needs in aging people with intellectual disability would be created. Through physical examination, laboratory examination, and use of screening and diagnostic psychiatric interviews, data were collected on 1050 participants, aged 50 years and over with borderline to profound intellectual disability, which was a near- representative sample for the total older population using formal intellectual disability care. This study was performed to give more insight into the prevalence and associations of cardiovascular risk factors, and the subsequent development of atherosclerosis, in older people with intellectual disability in a large unbiased population sample. Chapter 2 Overweight and obesity As obesity is a major health problem associated with increased cardiovascular disease risks, the prevalence of overweight, obesity and body fat percentage in older people with intellectual disability through measurement of Body Mass Index (BMI), waist circumference, waist to hip ratio and skin fold thickness was studied and compared with prevalence of overweight and obesity in the general population. Associations of overweight and obesity with participant and treatment characteristics (gender, age, level of intellectual disability, Down syndrome, autism, independent living, smoking, (instrumental) activities of daily living, physical activity and use of atypical antipsychotic medication) were studied using regression analyses. Among 945 participants, overweight and obesity were highly prevalent, with more obesity (26%) than in the general Dutch older population (10%) as measured by BMI, and 46-48% obesity as measured by waist circumference and waist to hip ratio respectively. Women, people with Down syndrome, higher age, less severe ID, autism, people who are able to eat independently, preparing meals and doing groceries independently, people with physical inactivity and use of atypical antipsychotics were significantly more at risk of being overweight or obese. Chapter 3 Hypertension, hypercholesterolemia, diabetes and the metabolic syndrome Hypertension, hypercholesterolemia and diabetes are important cardiovascular disease risk factors. Together with abdominal obesity they form the metabolic syndrome, which indicates metabolic disturbances, consisting of insulin resistance and accounting for a severe risk of cardiovascular disease. We determined the prevalence of cardiovascular risk factors and compared this with the prevalence in the same-aged general population. Furthermore we determined how many risk factors had not been previously diagnosed, and identified correlates of CVD risk factors (gender, age, level of ID, Down syndrome, independent living, activities of daily living, mobility, instrumental activities of daily living, physical activity, use of atypical antipsychotics, central obesity), using logistic regression analyses. Ninehundred-eighty people participated in this study. Hypertension (53%), diabetes (14%) and metabolic syndrome (45%) were present similarly as in the general Dutch population. Hypercholesterolemia was present less often (23%). Fifty percent of the people with hypertension had not been not previously diagnosed with this condition. Percentages for diabetes, hypercholesterolemia, and the metabolic syndrome were 45, 46 and 94 respectively. People who were more at risk for CVD risk factors were women, older people, people with obesity, people who lived more independently and people who were able to do groceries or prepare a meal independently. Chapter 4 Peripheral arterial disease Peripheral arterial disease, atherosclerosis distal from the aortic bifurcation, is associated with increased cardiovascular morbidity and mortality. We determined the prevalence of peripheral arterial disease, the rate of prior diagnoses, and correlations with participant characteristics, and compared the prevalence with peripheral arterial disease in the general Dutch population. Peripheral arterial disease was defined as an ankle-brachial index <0.9. After excluding those, who met the exclusion criteria, 629 participants remained. Peripheral arterial disease was present in 20.7% of the participants and 97% had not been diagnosed before. People with higher age, smokers and people who lived in central settings, walked with support and who were more dependent in activities of daily living were more at risk of peripheral arterial disease. The prevalence is higher than in the general population (17.4% of 562 eligible participants with ID, as compared to 8.1% of 917 Dutch participants of the PANDORA study, a pan-European study into the prevalence of peripheral arterial disease) through all age groups. Chapter 5 Association with anxiety and depression symptoms Depression and anxiety may be bidirectionally related to cardiovascular disease risk factors. Depression and anxiety may have biological effects causing glucose intolerance, fat accumulation and also lifestyle changes causing metabolic syndrome. But also the effects of diabetes, metabolic syndrome and subsequent cardiovascular disease may affect mood and anxiety. We studied the association between symptoms of anxiety and depression, among 990 participants who completed the screening instruments, with components of the metabolic syndrome, peripheral arterial disease and c-reactive protein. Of the 990 people who participated, 17% had symptoms of depression and 16% had symptoms of anxiety. In a multivariate logistic regression analysis a significant association was found between increased anxiety symptoms and diabetes only (OR 2.4, 95%CI 1.2-4.9). Chapter 6 Chronic kidney disease Prevalence and associations of chronic kidney disease were studied using creatinine and cystatin-C measurement in plasma. Glomerular filtration rate was calculated using the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. Equations based on creatinine (as the MDRD equation) may underestimate kidney dysfunction in people with sarcopenia, because low muscle mass leads to a low creatinine production. Therefore, also prevalence of chronic kidney disease was studied in the sarcopenic group, using different glomerular filtration rate equations. Prevalence of chronic kidney disease, among 635 participants, was 15.3%, which equals prevalence in the general Dutch population. In the group of participants with sarcopenia (n=82), the CKD-EPI equation based on creatinine and cystatin-C gave a higher prevalence of chronic kidney disease than did the MDRD equation, but confidence intervals were very wide. Chronic kidney disease was associated with higher age, Down syndrome, obesity, hypercholesterolemia and hypothyroid disease. Glomerular filtration rate should be measured in all older people with ID and polypharmacy, and in older people with ID and Down syndrome as part of the regular health checks. Moreover, if sarcopenia is present and information on GFR is required, this should not be measured based on creatinine only, but additional measures, such as cystatin-C, should be taken into account. Chapter 7 General discussion Some important cardiovascular disease risk factors, which are also a burden of disease by themselves: peripheral arterial disease, diabetes and obesity (in women), occur more often among aging people with intellectual disability than in the same aged general population. Other risk factors, hypertension, metabolic syndrome, obesity in men and chronic kidney disease, occur as frequently as in the general population. People who live more independently are more at risk for cardiovascular disease risk factors, which reflects lifestyle related factors, such as physical inactivity and unhealthy diet choices. Other possible related factors in the intellectually disabled population (such as use of atypical antipsychotics, mood and anxiety disorders, circadian rhythm disturbances, low vitamin D, effects of inactivity of the large muscles, chronic inflammation and frailty) are discussed. This study has shown that everyone who works with or for older people with intellectual disabilities should be well aware of the cardiovascular disease risk. An anticipating preventive policy should be embedded in the whole care for people with intellectual disability. This includes education on healthy lifestyle for personal care givers and for people with mild levels of intellectual disability. Furthermore, care providing organizations should incorporate targeted health promotion programs in daily care and activities. General practitioners and specialized physicians for people with intellectual disabilities should perform pro-active cardiovascular risk management, starting before the client is aged 50 years. This includes screening for and treatment of cardiovascular risk factors, peripheral arterial disease and kidney dysfunction. Recommendations for future research are provided to improve knowledge and care on cardiovascular disease risk factors and subsequent cardiovascular disease for older people with intellectual disabilities

Thread-Scalable Evaluation of Multi-Jet Observables

A leading-order, leading-color parton-level event generator is developed for use on a multi-threaded GPU. Speed-up factors between 150 and 300 are obtained compared to an unoptimized CPU-based implementation of the event generator. In this first paper we study the feasibility of a GPU-based event generator with an emphasis on the constraints imposed by the hardware. Some studies of Monte Carlo convergence and accuracy are presented for PP -> 2,...,10 jet observables using of the order of 1e11 events.Comment: 16 pages, 5 figures, 3 table

A Biased Review of Sociophysics

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Charged-Particle Multiplicities in Charged-Current Neutrino-- and Anti-Neutrino--Nucleus Interactions

The CHORUS experiment, designed to search for $\nu_{\mu}\to\nu_{\tau}$ oscillations, consists of a nuclear emulsion target and electronic detectors. In this paper, results on the production of charged particles in a small sample of charged-current neutrino-- and anti-neutrino--nucleus interactions at high energy are presented. For each event, the emission angle and the ionization features of the charged particles produced in the interaction are recorded, while the standard kinematic variables are reconstructed using the electronic detectors. The average multiplicities for charged tracks, the pseudo-rapidity distributions, the dispersion in the multiplicity of charged particles and the KNO scaling are studied in different kinematical regions. A study of quasi-elastic topologies performed for the first time in nuclear emulsions is also reported. The results are presented in a form suitable for use in the validation of Monte Carlo generators of neutrino--nucleus interactions.Comment: 17 pages, 5 figure

3D imaging of cell interactions with electrospun PLGA nanofiber membranes for bone regeneration

We acknowledge funding from the QMUL Pump-Priming Research Funding for Cross-Faculty Initiatives 2011-12 (EPSRC

The Science of Sungrazers, Sunskirters, and Other Near-Sun Comets

This review addresses our current understanding of comets that venture close to the Sun, and are hence exposed to much more extreme conditions than comets that are typically studied from Earth. The extreme solar heating and plasma environments that these objects encounter change many aspects of their behaviour, thus yielding valuable information on both the comets themselves that complements other data we have on primitive solar system bodies, as well as on the near-solar environment which they traverse. We propose clear definitions for these comets: We use the term near-Sun comets to encompass all objects that pass sunward of the perihelion distance of planet Mercury (0.307 AU). Sunskirters are defined as objects that pass within 33 solar radii of the Sun’s centre, equal to half of Mercury’s perihelion distance, and the commonly-used phrase sungrazers to be objects that reach perihelion within 3.45 solar radii, i.e. the fluid Roche limit. Finally, comets with orbits that intersect the solar photosphere are termed sundivers. We summarize past studies of these objects, as well as the instruments and facilities used to study them, including space-based platforms that have led to a recent revolution in the quantity and quality of relevant observations. Relevant comet populations are described, including the Kreutz, Marsden, Kracht, and Meyer groups, near-Sun asteroids, and a brief discussion of their origins. The importance of light curves and the clues they provide on cometary composition are emphasized, together with what information has been gleaned about nucleus parameters, including the sizes and masses of objects and their families, and their tensile strengths. The physical processes occurring at these objects are considered in some detail, including the disruption of nuclei, sublimation, and ionisation, and we consider the mass, momentum, and energy loss of comets in the corona and those that venture to lower altitudes. The different components of comae and tails are described, including dust, neutral and ionised gases, their chemical reactions, and their contributions to the near-Sun environment. Comet-solar wind interactions are discussed, including the use of comets as probes of solar wind and coronal conditions in their vicinities. We address the relevance of work on comets near the Sun to similar objects orbiting other stars, and conclude with a discussion of future directions for the field and the planned ground- and space-based facilities that will allow us to address those science topics

Dilepton mass spectra in p+p collisions at sqrt(s)= 200 GeV and the contribution from open charm

The PHENIX experiement has measured the electron-positron pair mass spectrum from 0 to 8 GeV/c^2 in p+p collisions at sqrt(s)=200 GeV. The contributions from light meson decays to e^+e^- pairs have been determined based on measurements of hadron production cross sections by PHENIX. They account for nearly all e^+e^- pairs in the mass region below 1 GeV/c^2. The e^+e^- pair yield remaining after subtracting these contributions is dominated by semileptonic decays of charmed hadrons correlated through flavor conservation. Using the spectral shape predicted by PYTHIA, we estimate the charm production cross section to be 544 +/- 39(stat) +/- 142(syst) +/- 200(model) \mu b, which is consistent with QCD calculations and measurements of single leptons by PHENIX.Comment: 375 authors from 57 institutions, 18 pages, 4 figures, 2 tables. Submitted to Physics Letters B. v2 fixes technical errors in matching authors to institutions. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Inclusive cross section and double helicity asymmetry for \pi^0 production in p+p collisions at sqrt(s)=200 GeV: Implications for the polarized gluon distribution in the proton

The PHENIX experiment presents results from the RHIC 2005 run with polarized proton collisions at sqrt(s)=200 GeV, for inclusive \pi^0 production at mid-rapidity. Unpolarized cross section results are given for transverse momenta p_T=0.5 to 20 GeV/c, extending the range of published data to both lower and higher p_T. The cross section is described well for p_T < 1 GeV/c by an exponential in p_T, and, for p_T > 2 GeV/c, by perturbative QCD. Double helicity asymmetries A_LL are presented based on a factor of five improvement in uncertainties as compared to previously published results, due to both an improved beam polarization of 50%, and to higher integrated luminosity. These measurements are sensitive to the gluon polarization in the proton, and exclude maximal values for the gluon polarization.Comment: 375 authors, 7 pages, 3 figures. Submitted to Phys. Rev. D, Rapid Communications. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

System Size and Energy Dependence of Jet-Induced Hadron Pair Correlation Shapes in Cu+Cu and Au+Au Collisions at sqrt(s_NN) = 200 and 62.4 GeV

We present azimuthal angle correlations of intermediate transverse momentum (1-4 GeV/c) hadrons from {dijets} in Cu+Cu and Au+Au collisions at sqrt(s_NN) = 62.4 and 200 GeV. The away-side dijet induced azimuthal correlation is broadened, non-Gaussian, and peaked away from \Delta\phi=\pi in central and semi-central collisions in all the systems. The broadening and peak location are found to depend upon the number of participants in the collision, but not on the collision energy or beam nuclei. These results are consistent with sound or shock wave models, but pose challenges to Cherenkov gluon radiation models.Comment: 464 authors from 60 institutions, 6 pages, 3 figures, 2 tables. Submitted to Physical Review Letters. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm