Calculating the Rate of Senescence From Mortality Data: An Analysis of Data From the ERA-EDTA Registry

The rate of senescence can be inferred from the acceleration by which mortality rates increase over age. Such a senescence rate is generally estimated from parameters of a mathematical model fitted to these mortality rates. However, such models have limitations and underlying assumptions. Notably, they do not fit mortality rates at young and old ages. Therefore, we developed a method to calculate senescence rates from the acceleration of mortality directly without modeling the mortality rates. We applied the different methods to age group–specific mortality data from the European Renal Association—European Dialysis and Transplant Association Registry, including patients with end-stage renal disease on dialysis, who are known to suffer from increased senescence rates (n = 302,455), and patients with a functioning kidney transplant (n = 74,490). From age 20 to 70, senescence rates were comparable when calculated with or without a model. However, when using non-modeled mortality rates, senescence rates were yielded at young and old ages that remained concealed when using modeled mortality rates. At young ages senescence rates were negative, while senescence rates declined at old ages. In conclusion, the rate of senescence can be calculated directly from non-modeled mortality rates, overcoming the disadvantages of an indirect estimation based on modeled mortality rates

Heart rate variability, but not heart rate, is associated with handgrip strength and mortality in older Africans at very low cardiovascular risk: A population-based study

A high heart rate and a low heart rate variability at rest are established predictors of various forms of functional impairment, morbidity, and mortality [1–6]. Two explanations can be given for these associations. On one hand, a high heart rate and a low heart rate variability are thought to reflect dysfunction of the flexible autonomic regulation of the heart rate in particular and of the body's functioning in general that arises during ageing [3–5]. On the other hand, a high heart rate and a low heart rate variability are brought about by cardiovascular risk factors, such as obesity, hyperlipidaemia, diabetes, hypertension, and physical inactivity [2,3,7–9]. Since research on heart rate and heart rate variability has almost exclusively been conducted in western populations with an affluent sedentary lifestyle and high prevalences of these risk factors, it has been difficult to determine whether or not heart rate and heart rate variability are associated with functional impairment, morbidity, and mortality independently of cardiovascular risk factors

Nitrate and the origin of saliva influence composition and short chain fatty acid production of oral microcosms

Nitrate is emerging as a possible health benefactor. Especially the microbial conversion of nitrate to nitrite in the oral cavity and the subsequent conversion to nitric oxide in the stomach are of interest in this regard. Yet, how nitrate influences the composition and biochemistry of the oral ecosystem is not fully understood. To investigate the effect of nitrate on oral ecology, we performed a 4-week experiment using the multiplaque artificial mouth (MAM) biofilm model. This model was inoculated with stimulated saliva of two healthy donors. Half of the microcosms (n = 4) received a constant supply of nitrate, while the other half functioned as control (n = 4). Additionally, all microcosms received a nitrate and sucrose pulse, each week, on separate days to measure nitrate reduction and acid formation. The bacterial composition of the microcosms was determined by 16S rDNA sequencing. The origin of the saliva (i.e., donor) showed to be the strongest determinant for the development of the microcosms. The supplementation of nitrate was related to a relatively high abundance of Neisseria in the microcosms of both donors, while Veillonella was highly abundant in the nitrate-supplemented microcosms of only one of the donors. The lactate concentration after sucrose addition was similarly high in all microcosms, irrespective of treatment or donor, while the concentration of butyrate was lower after nitrate addition in the nitrate-receiving microcosms. In conclusion, nitrate influences the composition and biochemistry of oral microcosms, although the result is strongly dependent on the inoculum

Universal neural field computation

Turing machines and G\"odel numbers are important pillars of the theory of computation. Thus, any computational architecture needs to show how it could relate to Turing machines and how stable implementations of Turing computation are possible. In this chapter, we implement universal Turing computation in a neural field environment. To this end, we employ the canonical symbologram representation of a Turing machine obtained from a G\"odel encoding of its symbolic repertoire and generalized shifts. The resulting nonlinear dynamical automaton (NDA) is a piecewise affine-linear map acting on the unit square that is partitioned into rectangular domains. Instead of looking at point dynamics in phase space, we then consider functional dynamics of probability distributions functions (p.d.f.s) over phase space. This is generally described by a Frobenius-Perron integral transformation that can be regarded as a neural field equation over the unit square as feature space of a dynamic field theory (DFT). Solving the Frobenius-Perron equation yields that uniform p.d.f.s with rectangular support are mapped onto uniform p.d.f.s with rectangular support, again. We call the resulting representation \emph{dynamic field automaton}.Comment: 21 pages; 6 figures. arXiv admin note: text overlap with arXiv:1204.546

Scarcity of atrial fibrillation in a traditional African population : a community-based study

Background: In western societies, atrial fibrillation is an increasingly common finding among the elderly. Established risk factors of atrial fibrillation include obesity, diabetes, hypertension, and cardiovascular disease. Atrial fibrillation has almost exclusively been studied in western populations where these risk factors are widely present. Therefore, we studied the epidemiology of atrial fibrillation in a traditional African community. Methods: In rural Ghana, among 924 individuals aged 50 years and older, we recorded electrocardiograms to detect atrial fibrillation. As established risk factors, we documented waist circumference, body mass index (BMI), capillary glucose level, blood pressure, and electrocardiographic myocardial infarction. In addition, we determined circulating levels of interleukin-6 (IL6), a proinflammatory cytokine, and C-reactive protein (CRP), a marker of systemic inflammation. We compared the risk factors with reference data from the USA. Results: Atrial fibrillation was detected in only three cases, equalling 0.3% (95% CI 0.1–1.0%). Waist circumference, BMI, and capillary glucose levels were very low. Hypertension and myocardial infarction were uncommon. Circulating levels of IL6 were similar, but those of CRP were lower compared with the USA. Conclusion: Atrial fibrillation is very scarce in this traditional African community. Its low prevalence compared with western societies can be explained by the rareness of its established risk factors, which are closely related to lifestyle, and by possible unmeasured differences in other risk factors or genetic factors.Wetensch. publicati

Handgrip strength, ageing and mortality in rural Africa

Background: muscle strength measured as handgrip strength declines with increasing age and predicts mortality. While handgrip strength is determined by lifestyle through nutrition and physical activity, it has almost exclusively been studied in western populations with a sedentary lifestyle. This study aims to investigate the relation between handgrip strength, ageing and mortality in a population characterised by a predominance of malnutrition and manual labour. Design: a population-based longitudinal study. Setting: a traditional African rural population in Ghana. Subjects: nine hundred and twenty-three community-dwelling individuals aged 50 and older. Methods: demographic characteristics were registered. At baseline, height, body mass index (BMI) and handgrip strength were measured and compared with those in a western reference population. Survival of the participants was documented during a period of up to 2 years. Results: handgrip strength was dependent on age, sex, height and BMI. Compared with the western reference population, handgrip strength was lower due to a lower height and BMI but declined over age similarly. Risk of mortality was lower in participants having higher handgrip strength, with a hazard ratio of 0.94 per kg increase (P = 0.002). After adjustment for age, sex, tribe, socio-economic status, drinking water source, height and BMI, only handgrip strength remained predictive of mortality. Conclusion: in a traditional rural African population characterised by malnutrition and manual labour, handgrip strength declines over age and independently predicts mortality similar to western populations. Handgrip strength can be used as a universal marker of ageing.Wetensch. publicati

Determinants of epidemiologic transition in rural Africa : the role of socioeconomic status and drinking water source

Background Many African countries experience a protracted epidemiologic transition, different from the classical transition in western societies. The factors driving this protracted transition are largely unknown. In northeast Ghana, we studied an ongoing epidemiologic transition and investigated the effects of socioeconomic status and drinking water source on the transition. Methods During a 9-year period, we followed a cohort of almost 30 000 individuals and collected information on mortality and fertility rates. In addition, using the standards set out by the WHO, we obtained the causes of death by verbal autopsy. Individuals were stratified according to their socioeconomic status and the households' use of an improved or unimproved drinking water source. Results Mortality rates decreased by −5.0% annually (p<0.001) and the main cause of death shifted from infectious to non-infectious diseases (p=0.014). General fertility rates and child-women ratios decreased annually by −12.7% (p<0.001) and −11.9% (p<0.001), respectively. There was no difference in the decline of mortality and fertility depending on socioeconomic status or drinking water source.Wetensch. publicati

The European DISABKIDS project: development of seven condition-specific modules to measure health related quality of life in children and adolescents

BACKGROUND: The European DISABKIDS project aims to enhance the Health Related Quality of Life (HRQoL) of children and adolescents with chronic medical conditions and their families. We describe the development of the seven cross-nationally tested condition-specific modules of the European DISABKIDS HRQoL instrument in a population of children and adolescents. The condition-specific modules are intended for use in conjunction with the DISABKIDS chronic generic module. METHODS: Focus groups were used to construct the pilot version of the DISABKIDS condition-specific HRQoL modules for asthma, juvenile idiopathic arthritis, atopic dermatitis, cerebral palsy, cystic fibrosis, diabetes and epilepsy. Analyses were conducted on pilot test data in order to construct field test versions of the modules. A series of factor analyses were run, first, to determine potential structures for each condition-specific module, and, secondly, to select a reduced number of items from the pilot test to be included in the field test. Post-field test analyses were conducted to retest the domain structure for the final DISABKIDS condition-specific modules. RESULTS: The DISABKIDS condition-specific modules were tested in a pilot study of 360 respondents, and subsequently in a field test of 1152 respondents in 7 European countries. The final condition-specific modules consist of an 'Impact' domain and an additional domain (e.g. worry, stigma, treatment) with between 10 to 12 items in total. The Cronbach's alpha of the final domains was found to vary from 0.71 to 0.90. CONCLUSION: The condition-specific modules of the DISABKIDS instrument were developed through a step-by-step process including cognitive interview, clinical expertise, factor analysis, correlations and internal consistency. A cross-national pilot and field test were necessary to collect these data. In general, the internal consistency of the domains was satisfactory to high. In future, the DISABKIDS instrument may serve as a useful tool with which to assess HRQoL in children and adolescents with a chronic condition. The condition-specific modules can be used in conjunction with the DISABKIDS chronic generic module

Feasibility and effectiveness of trifluridine/tipiracil in metastatic colorectal cancer: real-life data from The Netherlands

Background: The RECOURSE trial showed clinical efficacy for trifluridine/tipiracil for refractory metastatic colorectal cancer patients. We assessed the feasibility and effectiveness of trifluridine/tipiracil in daily clinical practice in The Netherlands. Methods: Medical records of patients from 17 centers treated in the trifluridine/tipiracil compassionate use program were reviewed and checked for RECOURSE eligibility criteria. Baseline characteristics, safety, and survival times were compared, and prespecified baseline characteristics were tested in multivariate analyses for prognostic significance on overall survival (OS). Results: A total of 136 patients with a median age of 62 years were analyzed. Forty-three patients (32%) did not meet the RECOURSE eligibility criteria for not having received all prior standard treatments (n = 35, 26%) and/or ECOG performance status (PS) 2 (n = 12, 9%). The most common grade ≥3 toxicities were neutropenia (n = 44, 32%), leukopenia (n = 8, 6%), anemia (n = 7, 5%), and fatigue (n = 7, 5%). Median progression-free survival (PFS) and median OS were 2.1 (95% CI, 1.8–2.3) and 5.4 months (95% CI, 4.0–6.9), respectively. Patients with ECOG PS 2 had a worse median OS (3.2 months) compared to patients with ECOG PS 0–1 (5.9 months). ECOG PS, KRAS-mutation status, white blood cell count, serum lactate dehydrogenase, and alkaline phosphatase were prognostic factors for OS. Conclusions: Our data show that treatment with trifluridine/tipiracil in daily clinical practice is feasible and safe. Differences in patient characteristics between our population and the RECOURSE study population should be taken into account in the interpretation of survival data. Our results argue against the use of trifluridine/tipiracil in patients with ECOG PS 2. Funding: Johannes J.M. Kwakman received an unrestricted research grant from Servier