Determinants of Healthy Ageing: Studies of Disability and Survival among the Elderly

The increase in life expectancy over the last century is one of society’s major achievements. In particular in developed countries, though increasingly in developing countries, a higher life expectancy and a reduction in birth rates result in an ageing of the population, i.e. the shift of the median age in the population towards older ages. Thus, while human population growth approximates 1.2% annually, this population growth is not constant across all ages. Annually, the population older than 60 increases by 2 – 3%, while the population older than 80 increases by 4%. By 2050, more than one third of all Europeans are expected to be older than 60 years.[1] These demographic trends are supported by evidence showing that the recent increases in life expectancy in Western countries can mainly be attributed to better survival among the elderly. Ageing of the population poses a challenge for both developed and developing countries. The goal of this thesis is to identify risk factors for disability, disease-free survival, mortality and longevity. Specifically we asked the following research questions: 1. What genetic loci are associated with longevity and time to death and disease? (Chapter 2) 2. Do body mass index, physical activity, and happiness influence time to death and time spent with disability? (Chapter 3) 3. Which set of risk factors best predicts death and how do different groups of risk factors compare in their predictive power? (Chapter 4

Nonequilibrium Spin Dynamics in the Ferromagnetic Kondo Model

Motivated by recent experiments on molecular quantum dots we investigate the relaxation of pure spin states when coupled to metallic leads. Under suitable conditions these systems are well described by a ferromagnetic Kondo model. Using two recently developed theoretical approaches, the time-dependent numerical renormalization group and an extended ow equation method, we calculate the real-time evolution of a Kondo spin into its partially screened steady state. We obtain exact analytical results which agree well with numerical implementations of both methods. Analytical expressions for the steady state magnetization and the dependence of the long-time relaxation on microscopic parameters are established. We find the long-time relaxation process to be much faster in the regime of anisotropic Kondo couplings. The steady state magnetization is found to deviate significantly from its thermal equilibrium value.Comment: 4 pages, 3 figures, final version as accepted by Physical Review Letter

Human spaceflight: to infertility and beyond

Garrett-Bakelman FE et al, demonstrated a spectrum of molecular and physiological changes attributed to spaceflight in their recently published “NASA Twins Study”.1 During his 340 days in space onboard the International Space Station (ISS), one of a pair of monozygotic twins was not only challenged by noise, isolation, hypoxia, and alterations in the circadian rhythm, but more importantly the exposure to ionizing radiation (IR) and microgravity. Terrestrials are subjected constantly to surface gravity and most if not all physiological processes have adapted accordingly. It is therefore easy to envisage that weightlessness can have consequences for space travellers.

Unconditional cash transfers for assistance in humanitarian disasters: effects on the use of health services and health outcomes in low- and middle-income countries

BACKGROUND: Unconditional cash transfers (UCTs) are a common social protection intervention that increases income, a key social determinant of health, in disaster contexts in low- and middle-income countries (LMICs). OBJECTIVES: To assess the effects of UCTs in improving health services use, health outcomes, social determinants of health, health care expenditure, and local markets and infrastructure in LMICs. We also compared the relative effectiveness of UCTs delivered in-hand with in-kind transfers, conditional cash transfers, and UCTs paid through other mechanisms. SEARCH METHODS: We searched 17 academic databases, including the Cochrane Public Health Group Specialised Register, the Cochrane Database of Systematic Reviews (The Cochrane Library 2014, Issue 7), MEDLINE, and EMBASE between May and July 2014 for any records published up until 4 May 2014. We also searched grey literature databases, organisational websites, reference lists of included records, and academic journals, as well as seeking expert advice. SELECTION CRITERIA: We included randomised and quasi-randomised controlled trials (RCTs), as well as cohort, interrupted time series, and controlled before-and-after studies (CBAs) on UCTs in LMICs. Primary outcomes were the use of health services and health outcomes. DATA COLLECTION AND ANALYSIS: Two authors independently screened all potentially relevant records for inclusion criteria, extracted the data, and assessed the included studies\u27 risk of bias. We requested missing information from the study authors. MAIN RESULTS: Three studies (one cluster-RCT and two CBAs) comprising a total of 13,885 participants (9640 children and 4245 adults) as well as 1200 households in two LMICs (Nicaragua and Niger) met the inclusion criteria. They examined five UCTs between USD 145 and USD 250 (or more, depending on household characteristics) that were provided by governmental, non-governmental or research organisations during experiments or pilot programmes in response to droughts. Two studies examined the effectiveness of UCTs, and one study examined the relative effectiveness of in-hand UCTs compared with in-kind transfers and UCTs paid via mobile phone. Due to the methodologic limitations of the retrieved records, which carried a high risk of bias and very serious indirectness, we considered the body of evidence to be of very low overall quality and thus very uncertain across all outcomes.Depending on the specific health services use and health outcomes examined, the included studies either reported no evidence that UCTs had impacted the outcome, or they reported that UCTs improved the outcome. No single outcome was reported by more than one study. There was a very small increase in the proportion of children who received vitamin or iron supplements (mean difference (MD) 0.10 standard deviations (SDs), 95% confidence interval (CI) 0.06 to 0.14) and on the child\u27s home environment, as well as clinically meaningful, very large reductions in the chance of child death (hazard ratio (HR) 0.26, 95% CI 0.10 to 0.66) and the incidence of severe acute malnutrition (HR 0.44, 95% CI 0.24 to 0.80). There was also a moderate reduction in the number of days children spent sick in bed (MD - 0.36 SDs, 95% CI - 0.62 to - 0.10). There was no evidence for any effect on the proportion of children receiving deworming drugs, height for age among children, adults\u27 level of depression, or the quality of parenting behaviour. No adverse effects were identified. The included comparisons did not examine several important outcomes, including food security and equity impacts.With regard to the relative effectiveness of UCTs compared with a food transfer providing a relatively high total caloric value, there was no evidence that a UCT had any effect on the chance of child death (HR 2.27, 95% CI 0.69 to 7.44) or severe acute malnutrition (HR 1.15, 95% CI 0.67 to 1.99). A UCT paid in-hand led to a clinically meaningful, moderate increase in the household dietary diversity score, compared with the same UCT paid via mobile phone (difference-in-differences estimator 0.43 scores, 95% CI 0.06 to 0.80), but there was no evidence for an effect on social determinants of health, health service expenditure, or local markets and infrastructure. AUTHORS\u27 CONCLUSIONS: Additional high-quality evidence (especially RCTs of humanitarian disaster contexts other than droughts) is required to reach clear conclusions regarding the effectiveness and relative effectiveness of UCTs for improving health services use and health outcomes in humanitarian disasters in LMICs

Unconditional cash transfers for reducing poverty and vulnerabilities: effect on use of health services and health outcomes in low-and middle-income countries

Background Unconditional cash transfers (UCTs; provided without obligation) for reducing poverty and vulnerabilities (e.g. orphanhood, old age or HIV infection) are a type of social protection intervention that addresses a key social determinant of health (income) in low‐ and middle‐income countries (LMICs). The relative effectiveness of UCTs compared with conditional cash transfers (CCTs; provided so long as the recipient engages in prescribed behaviours such as using a health service or attending school) is unknown. Objectives To assess the effects of UCTs for improving health services use and health outcomes in vulnerable children and adults in LMICs. Secondary objectives are to assess the effects of UCTs on social determinants of health and healthcare expenditure and to compare to effects of UCTs versus CCTs. Search methods We searched 17 electronic academic databases, including the Cochrane Public Health Group Specialised Register, the Cochrane Database of Systematic Reviews (the Cochrane Library 2017, Issue 5), MEDLINE and Embase, in May 2017. We also searched six electronic grey literature databases and websites of key organisations, handsearched key journals and included records, and sought expert advice. Selection criteria We included both parallel group and cluster‐randomised controlled trials (RCTs), quasi‐RCTs, cohort and controlled before‐and‐after (CBAs) studies, and interrupted time series studies of UCT interventions in children (0 to 17 years) and adults (18 years or older) in LMICs. Comparison groups received either no UCT or a smaller UCT. Our primary outcomes were any health services use or health outcome. Data collection and analysis Two reviewers independently screened potentially relevant records for inclusion criteria, extracted data and assessed the risk of bias. We tried to obtain missing data from study authors if feasible. For cluster‐RCTs, we generally calculated risk ratios for dichotomous outcomes from crude frequency measures in approximately correct analyses. Meta‐analyses applied the inverse variance or Mantel‐Haenszel method with random effects. We assessed the quality of evidence using the GRADE approach. Main results We included 21 studies (16 cluster‐RCTs, 4 CBAs and 1 cohort study) involving 1,092,877 participants (36,068 children and 1,056,809 adults) and 31,865 households in Africa, the Americas and South‐East Asia in our meta‐analyses and narrative synthesis. The 17 types of UCTs we identified, including one basic universal income intervention, were pilot or established government programmes or research experiments. The cash value was equivalent to 1.3% to 53.9% of the annualised gross domestic product per capita. All studies compared a UCT with no UCT, and three studies also compared a UCT with a CCT. Most studies carried an overall high risk of bias (i.e. often selection and/or performance bias). Most studies were funded by national governments and/or international organisations. Throughout the review, we use the words \u27probably\u27 to indicate moderate‐quality evidence, \u27may/maybe\u27 for low‐quality evidence, and \u27uncertain\u27 for very low‐quality evidence. UCTs may not have impacted the likelihood of having used any health service in the previous 1 to 12 months, when participants were followed up between 12 and 24 months into the intervention (risk ratio (RR) 1.04, 95% confidence interval (CI) 1.00 to 1.09, P = 0.07, 5 cluster‐RCTs, N = 4972, I² = 2%, low‐quality evidence). At one to two years, UCTs probably led to a clinically meaningful, very large reduction in the likelihood of having had any illness in the previous two weeks to three months (odds ratio (OR) 0.73, 95% CI 0.57 to 0.93, 5 cluster‐RCTs, N = 8446, I² = 57%, moderate‐quality evidence). Evidence from five cluster‐RCTs on food security was too inconsistent to be combined in a meta‐analysis, but it suggested that at 13 to 24 months\u27 follow‐up, UCTs could increase the likelihood of having been food secure over the previous month (low‐quality evidence). UCTs may have increased participants\u27 level of dietary diversity over the previous week, when assessed with the Household Dietary Diversity Score and followed up 24 months into the intervention (mean difference (MD) 0.59 food categories, 95% CI 0.18 to 1.01, 4 cluster‐RCTs, N = 9347, I² = 79%, low‐quality evidence). Despite several studies providing relevant evidence, the effects of UCTs on the likelihood of being moderately stunted and on the level of depression remain uncertain. No evidence was available on the effect of a UCT on the likelihood of having died. UCTs probably led to a clinically meaningful, moderate increase in the likelihood of currently attending school, when assessed at 12 to 24 months into the intervention (RR 1.06, 95% CI 1.03 to 1.09, 6 cluster‐RCTs, N = 4800, I² = 0%, moderate‐quality evidence). The evidence was uncertain for whether UCTs impacted livestock ownership, extreme poverty, participation in child labour, adult employment or parenting quality. Evidence from six cluster‐RCTs on healthcare expenditure was too inconsistent to be combined in a meta‐analysis, but it suggested that UCTs may have increased the amount of money spent on health care at 7 to 24 months into the intervention (low‐quality evidence). The effects of UCTs on health equity (or unfair and remedial health inequalities) were very uncertain. We did not identify any harms from UCTs. Three cluster‐RCTs compared UCTs versus CCTs with regard to the likelihood of having used any health services, the likelihood of having had any illness or the level of dietary diversity, but evidence was limited to one study per outcome and was very uncertain for all three. Authors\u27 conclusions This body of evidence suggests that unconditional cash transfers (UCTs) may not impact a summary measure of health service use in children and adults in LMICs. However, UCTs probably or may improve some health outcomes (i.e. the likelihood of having had any illness, the likelihood of having been food secure, and the level of dietary diversity), one social determinant of health (i.e. the likelihood of attending school), and healthcare expenditure. The evidence on the relative effectiveness of UCTs and CCTs remains very uncertain

Black hole masses and enrichment of z ~ 6 SDSS quasars

We present sensitive near-infrared spectroscopic observations for a sample of five z ~ 6 quasars. These are amongst the most distant, currently known quasars in the universe. The spectra have been obtained using ISAAC at the VLT and include the CIV, MgII and FeII lines. We measure the FeII/MgII line ratio, as an observational proxy for the Fe/alpha element ratio. We derive a ratio of 2.7+/-0.8 for our sample, which is similar to that found for lower redshift quasars, i.e., we provide additional evidence for the lack of evolution in the FeII/MgII line ratio of quasars up to the highest redshifts. This result demonstrates that the sample quasars must have undergone a major episode of iron enrichment in less than one Gyr and star formation must have commenced at z > 8. The linewidths of the MgII and CIV lines give two estimates for the black hole masses. A third estimate is given by assuming that the quasars emit at their Eddington luminosity. The derived masses using these three methods agree well, implying that the quasars are not likely to be strongly lensed. We derive central black hole masses of 0.3-5.2 10^9 solar masses. We use the difference between the redshift of MgII (a proxy for the systemic redshift of the quasar) and the onset of the Gunn Peterson trough to derive the extent of the ionized Stromgren spheres around our target quasars. The derived physical radii are about five Mpc. Using a simple ionization model, the emission of the central quasars would need of order 10^6-10^8 year to create these cavities in a surrounding intergalactic medium with a neutral fraction between 0.1 and 1.0. As the e-folding time scale for the central accreting black hole is on the order of a few times 10^7 year, it can grow by one e-folding or less within this time span.Comment: Accepted by ApJ, 15 pages, 8 figure

Relapse Prevention Intervention after Suicidal Event (RISE): Feasibility study of a psychotherapeutic short-term program for inpatients after a recent suicide attempt

Recent research suggests that treating only mental disorders may not be sufficient to reduce the risk for future suicidal behavior in patients with a suicide attempt(s). It is therefore necessary to pay special therapeutic attention to past suicidal acts. Thus, the newly developed RISE (Relapse Prevention Intervention after Suicidal Event) program was built on the most effective components of existing psychotherapeutic and psychosocial interventions according to our current meta-analysis. The RISE program consists of five individual sessions designed for the acute psychiatric inpatient setting. The main goals of the treatment are to decrease future suicidal events and to improve patients' ability to cope with future suicidal crises. In the present study, feasibility and acceptance of the RISE program were investigated as well as its clinical effects on suicidal ideations, mental pain, self-efficacy and depressive symptoms. We recruited a sample of 27 inpatients of the Department of Psychiatry and Psychotherapy, University Hospital Jena, Germany. The final sample consisted of 20 patients hospitalized for a recent suicide attempt, including 60 percent of multiple attempters. The data collection included a structured interview and a comprehensive battery of questionnaires to evaluate the feasibility and acceptance of the RISE program as well as associated changes in clinical symptoms. A follow-up examination was carried out after 6 months. Considering the low dropout rate and the overall positive evaluation, the RISE program was highly accepted in a sample of severely impaired patients. The present study also demonstrated that the levels of suicidal ideations, mental pain, depressive symptoms, and hopelessness decreased significantly after RISE. Since all of these clinical parameters are associated with the risk of future suicidal behavior, a potential suicide-preventive effect of the intervention can be inferred from the present findings. The positive results of the follow-up assessment after 6 months point in the same direction. In addition, RISE treatment increased self-efficacy in patients, which is an important contributor for better coping with future suicidal crises. Thus, present study demonstrate that RISE is a suitable therapy program for the treatment of patients at high risk for suicidal behavior in an acute inpatient setting

Resolutions of C^n/Z_n Orbifolds, their U(1) Bundles, and Applications to String Model Building

We describe blowups of C^n/Z_n orbifolds as complex line bundles over CP^{n-1}. We construct some gauge bundles on these resolutions. Apart from the standard embedding, we describe U(1) bundles and an SU(n-1) bundle. Both blowups and their gauge bundles are given explicitly. We investigate ten dimensional SO(32) super Yang-Mills theory coupled to supergravity on these backgrounds. The integrated Bianchi identity implies that there are only a finite number of U(1) bundle models. We describe how the orbifold gauge shift vector can be read off from the gauge background. In this way we can assert that in the blow down limit these models correspond to heterotic C^2/Z_2 and C^3/Z_3 orbifold models. (Only the Z_3 model with unbroken gauge group SO(32) cannot be reconstructed in blowup without torsion.) This is confirmed by computing the charged chiral spectra on the resolutions. The construction of these blowup models implies that the mismatch between type-I and heterotic models on T^6/Z_3 does not signal a complication of S-duality, but rather a problem of type-I model building itself: The standard type-I orbifold model building only allows for a single model on this orbifold, while the blowup models give five different models in blow down.Comment: 1+27 pages LaTeX, 2 figures, some typos correcte