Multistate modelling extended by behavioural rules: An application to migration.

We propose to extend demographic multistate models by adding a behavioural element: behavioural rules explain intentions and thus transitions. Our framework is inspired by the Theory of Planned Behaviour. We exemplify our approach with a model of migration from Senegal to France. Model parameters are determined using empirical data where available. Parameters for which no empirical correspondence exists are determined by calibration. Age- and period-specific migration rates are used for model validation. Our approach adds to the toolkit of demographic projection by allowing for shocks and social influence, which alter behaviour in non-linear ways, while sticking to the general framework of multistate modelling. Our simulations yield that higher income growth in Senegal leads to higher emigration rates in the medium term, while a decrease in fertility yields lower emigration rates.

Modelling and simulating decision processes of linked lives: An approach based on concurrent processes and stochastic race.

Individuals' decision processes play a central role in understanding modern migration phenomena and other demographic processes. Their integration into agent-based computational demography depends largely on suitable support by a modelling language. We are developing the Modelling Language for Linked Lives (ML3) to describe the diverse decision processes of linked lives succinctly in continuous time. The context of individuals is modelled by networks the individual is part of, such as family ties and other social networks. Central concepts, such as behaviour conditional on agent attributes, age-dependent behaviour, and stochastic waiting times, are tightly integrated in the language. Thereby, alternative decisions are modelled by concurrent processes that compete by stochastic race. Using a migration model, we demonstrate how this allows for compact description of complex decisions, here based on the Theory of Planned Behaviour. We describe the challenges for the simulation algorithm posed by stochastic race between multiple concurrent complex decisions.

Emigration Rates From Sample Surveys: An Application to Senegal.

What is the emigration rate of a country, and how reliable is that figure? Answering these questions is not at all straightforward. Most data on international migration are census data on foreign-born population. These migrant stock data describe the immigrant population in destination countries but offer limited information on the rate at which people leave their country of origin. The emigration rate depends on the number leaving in a given period and the population at risk of leaving, weighted by the duration at risk. Emigration surveys provide a useful data source for estimating emigration rates, provided that the estimation method accounts for sample design. In this study, emigration rates and confidence intervals are estimated from a sample survey of households in the Dakar region in Senegal, which was part of the Migration between Africa and Europe survey. The sample was a stratified two-stage sample with oversampling of households with members abroad or return migrants. A combination of methods of survival analysis (time-to-event data) and replication variance estimation (bootstrapping) yields emigration rates and design-consistent confidence intervals that are representative for the study population.

Decision-Making in Agent-Based Models of Migration: State of the Art and Challenges.

We review agent-based models (ABM) of human migration with respect to their decision-making rules. The most prominent behavioural theories used as decision rules are the random utility theory, as implemented in the discrete choice model, and the theory of planned behaviour. We identify the critical choices that must be made in developing an ABM, namely the modelling of decision processes and social networks. We also discuss two challenges that hamper the widespread use of ABM in the study of migration and, more broadly, demography and the social sciences: (a) the choice and the operationalisation of a behavioural theory (decision-making and social interaction) and (b) the selection of empirical evidence to validate the model. We offer advice on how these challenges might be overcome.

Compression or expansion of dementia in Germany? An observational study of short-term trends in incidence and death rates of dementia between 2006/07 and 2009/10 based on German health insurance data.

INTRODUCTION: There have been recent reports about a decline in dementia incidence, but only little is known about trends in the mortality of patients with dementia. Only the simultaneous analysis of both trends can inform whether the reported decline in dementia has led to a compression of dementia into higher ages. METHODS: We used health claims data from the largest public health insurer in Germany over the two time periods 2004/07 and 2007/10. Dementia was defined according to the International Classification of Disease 10th revision (ICD-10) numbers G30, G31.0, G31.82, G23.1, F00, F01, F02, F03 and F05.1 or by a prescription of cholinesterase inhibitors or memantine or both. In the two time periods, we observed 502,065 person-years of exposure and 10,881 incident dementia cases and 10,013 person-years of exposure among the newly demented and 3049 deaths. We estimated the relative risks of the two time periods applying proportional hazard models and calculated years with or without dementia using the illness-death model. RESULTS: Dementia incidence was significantly higher in 2006/07 than in 2009/10, whereas mortality with dementia tended to be lower in the first period, albeit statistically significant among women only. Mortality without dementia tended to be higher in the first period for men and remained stable for women. Combining these trends, we found that at age 65 remaining life years with dementia were compressed by a yearly 0.4 months for men and 1.4 months for women. At the same time, remaining life years without dementia increased by a yearly 1.4 months for men and 1.1 months for women. CONCLUSIONS: This study provides evidence that the increase in dementia-free life years went together with an absolute compression of life years with dementia. This positive trend was particularly strong among women. Results were controlled for trends in multi-morbidity and care need, suggesting that the postponement in dementia incidence is not simply caused by a delay in diagnosis.

The proteome of erythrocyte-derived microparticles from plasma: new clues for erythrocyte aging and vesiculation.

Vesicle formation is an integral part of the physiological erythrocyte aging process. Recent biophysical and immunochemical data have suggested that vesicles originate by the extrusion of membrane patches that, during aging, have become damaged and simultaneously enriched in removal signals. Thereby, vesiculation may serve to postpone the untimely removal of functional cells. As a first step toward the identification of the underlying mechanisms, we isolated erythrocyte-derived vesicles from plasma by fluorescence-activated cell sorting, analyzed their proteome by mass spectrometry, and compared this with the membrane proteomes of erythrocytes that were separated according to cell age. The presence of band 3 and actin in the vesicles together with the absence of almost all other integral membrane and cytoskeletal proteins, and the specific, aging-associated alterations in band 3 aggregation and degradation shown by proteomics as well as immunochemistry, all suggest that the erythrocyte aging process harbors a specific, band 3-centered mechanism for vesicle generation. The age-related recruitment of plasma proteins, proteins of the ubiquitin-proteasome system, and small G proteins to the erythrocyte membrane supports the hypothesis that modification of band 3 and/or degradation initiate vesiculation, and the subsequent recognition and fast removal of vesicles by the immune system. This article is part of a Special Issue entitled: Integrated omics.

Higher education delays and shortens cognitive impairment: a multistate life table analysis of the US Health and Retirement Study.

Improved health may extend or shorten the duration of cognitive impairment by postponing incidence or death. We assess the duration of cognitive impairment in the US Health and Retirement Study (1992-2004) by self reported BMI, smoking and levels of education in men and women and three ethnic groups. We define multistate life tables by the transition rates to cognitive impairment, recovery and death and estimate Cox proportional hazard ratios for the studied determinants. 95% confidence intervals are obtained by bootstrapping. 55 year old white men and women expect to live 25.4 and 30.0 years, of which 1.7 [95% confidence intervals 1.5; 1.9] years and 2.7 [2.4; 2.9] years with cognitive impairment. Both black men and women live 3.7 [2.9; 4.5] years longer with cognitive impairment than whites, Hispanic men and women 3.2 [1.9; 4.6] and 5.8 [4.2; 7.5] years. BMI makes no difference. Smoking decreases the duration of cognitive impairment with 0.8 [0.4; 1.3] years by high mortality. Highly educated men and women live longer, but 1.6 years [1.1; 2.2] and 1.9 years [1.6; 2.6] shorter with cognitive impairment than lowly educated men and women. The effect of education is more pronounced among ethnic minorities. Higher life expectancy goes together with a longer period of cognitive impairment, but not for higher levels of education: that extends life in good cognitive health but shortens the period of cognitive impairment. The increased duration of cognitive impairment in minority ethnic groups needs further study, also in Europe.

Susceptibility to hyperosmotic stress-induced phosphatidylserine exposure increases during red blood cell storage.

BACKGROUND: During storage of red blood cell (RBCs) before transfusion, RBCs undergo a series of structural and functional changes that include the exposure of phosphatidylserine (PS), a potent removal signal. It was postulated that, during blood bank storage, the susceptibility to stress-induced PS exposure increases, thereby rendering a considerable fraction of the RBCs susceptible to rapid removal after transfusion. STUDY DESIGN AND METHODS: RBCs were processed and stored following standard Dutch blood bank procedures. Samples were taken every week for up to 6 weeks and exposed to various stress conditions, such as hyperosmotic shock and energy depletion. The effect of these treatments on PS exposure was measured by flow cytometric analysis of annexin V binding. The same analyses were performed on RBCs that had been separated according to density using discontinuous Percoll gradients. RESULTS: During storage under blood bank conditions, RBCs become increasingly susceptible to loss of phospholipid asymmetry induced by hyperosmotic shock and energy depletion. Especially the RBCs of higher densities, that have a smaller volume and an increased HbA1c content as is typical of aged RBCs, become increasingly susceptible with storage time. CONCLUSIONS: During storage, RBCs develop an increased susceptibility to stress-induced loss of phospholipid asymmetry that is especially associated with an aging phenotype. This increased susceptibility may be responsible for the rapid disappearance of a considerable fraction of the RBCs during the first 24 hours after transfusion.

Smoking kills, obesity disables: a multistate approach of the US Health and Retirement Survey.

Increasing BMI causes concerns about the consequences for health care. Decreasing cardiovascular mortality has lowered obesity-related mortality, extending duration of disability. We hypothesized increased duration of disability among overweight and obese individuals. We estimated age-, risk-, and state-dependent probabilities of activities of daily living (ADL) disability and death and calculated multistate life tables, resulting in the comprehensive measure of life years with and without ADL disability. We used prospective data of 16,176 white adults of the Health and Retirement Survey (HRS). Exposures were self-reported BMI and for comparison smoking status and levels of education. Outcomes were years to live with and without ADL disability at age 55. The reference categories were high normal weight (BMI: 23-24.9), nonsmoking and high education. Mild obesity (BMI: 30-34.9) did not change total life expectancy (LE) but exchanged disabled for disability-free years. Mild obesity decreased disability-free LE with 2.7 (95% confidence limits 1.2; 3.2) year but increased LE with disability with 2.0 (0.6; 3.4) years among men. Among women, BMI of 30 to 34.9 decreased disability-free LE with 3.6 (2.1; 5.1) year but increased LE with disability with 3.2 (1.6;4.8) years. Overweight (BMI: 25-29.9) increases LE with disability for women only, by 2.1 (0.8; 3.3) years). Smoking compressed disability by high mortality. Smoking decreased LE with 7.2 years, and LE with disability with 1.3 (0.5; 2.5) years (men) and 1.4 (0.3; 2.6) years (women). A lower education decreased disability-free life, but not duration of ADL disability. In the aging baby boom, higher BMI will further increase care dependence.

The burden of mortality of obesity at middle and old age is small. A life table analysis of the US Health and Retirement Survey.

The evidence of effect of overweight and obesity on mortality at middle and old age is conflicting. The increased relative risk of cardiovascular disease and diabetes for overweight and obese individuals compared to normal weight is well documented, but the absolute risk of cardiovascular death has decreased spectacularly since the 1980s. We estimate the burden of mortality of obesity among middle and old aged adults in the Health and Retirement Survey (HRS), a US prospective longitudinal study. We calculate univariate and multivariate age-specific probabilities and proportional hazard ratios of death in relation to self-reported body mass index (BMI), smoking and education. The life table translates age specific adjusted event rates in survival times, dependent on risk factor distributions (smoking, levels of education and self reported BMI). 95% confidence intervals are calculated by bootstrapping. The highest life expectancy at age 55 was found in overweight (BMI 25-29.9), highly educated non smokers: 30.7 (29.5-31.9) years (men) and 33.2 (32.1-34.3) (women), slightly higher than a BMI 23-24.9 in both sexes. Smoking decreased the population life expectancy with 3.5 (2.7-4.4) years (men) and 1.8 (1.0-2.5) years (women). Less than optimal education cost men and women respectively 2.8 (2.1-3.6) and 2.6 (1.6-3.6) years. Obesity and low normal weight decreased population life expectancy respectively by 0.8 (0.2-1.3) and 0.8 (0.0-1.5) years for men and women in a contemporary, US population. The burden of mortality of obesity is limited, compared to smoking and low education.

Erythrocyte vesiculation: a self-protective mechanism?

Previous studies demonstrated that 20% of haemoglobin is lost from circulating erythrocytes during their total lifespan by vesiculation. To study whether removal molecules other than membrane-bound haemoglobin were present in erythrocyte-derived vesicles, flow cytometry and immunoblot analysis were employed to examine the presence of phosphatidylserine (PS) and IgG, and senescent cell antigens respectively. It was demonstrated that 67% of glycophorin A-positive vesicles exposed PS, and that half of these vesicles also contained IgG. Immunoblot analysis revealed the presence of a breakdown product of band 3 that reacted with antibodies directed against senescent erythrocyte antigen-associated band 3 sequences. In contrast, only the oldest erythrocytes contained senescent cell antigens and IgG, and only 0.1% of erythrocytes, of all ages, exposed PS. It was concluded that vesiculation constitutes a mechanism for the removal of erythrocyte membrane patches containing removal molecules, thereby postponing the untimely elimination of otherwise healthy erythrocytes. Consequently, these same removal molecules mediate the rapid removal of erythrocyte-derived vesicles from the circulation.

Association between age at menarche and early-life nutritional status in rural Bangladesh.

Age at menarche is associated with anthropometry in adolescence. Recently, there has been growing support for the hypothesis that timing of menarche may be set early in life but modified by changes in body size and composition in childhood. To evaluate this, a cohort of 255 girls aged <5 years recruited in 1988 were followed up in 2001 in Matlab, Bangladesh. The analysis was based on nutritional status as assessed by anthropometry and recalled age at menarche. Data were examined using lifetable techniques and the Cox regression model. The association between nutritional status indicators and age at menarche was examined in a multivariate model adjusting for potential confounding variables. Censored cases were accounted for. The median age at menarche was 15.1 years. After controlling for early-life predictors (birth size, childhood underweight, childhood stunting) it appeared that adolescent stunting stood out as the most important determinant of age at menarche. Adolescent stunting still resonates from the effect of stunting in early childhood (OR respectively 2.63 (p<0.01 CI: 1.32-5.24) and 8.47 (p<0.001 CI: 3.79-18.93) for moderately and severely stunted under-fives as compared with the reference category). Birth size was not a significant predictor of age at menarche. It is concluded that age at menarche is strongly influenced by nutritional status in adolescence, notably the level of stunting, which is in turn highly dependent on the level of stunting in early childhood. A 'late' menarche due to stunting may be detrimental for reproductive health in case of early childbearing because of the association between height and pelvic size.

Coeliac disease in Dutch patients with Hashimoto's thyroiditis and vice versa.

AIM: To define the association between Hashimoto's thyroiditis and coeliac disease in Dutch patients. METHODS: A total of 104 consecutive patients with Hashimoto's thyroiditis underwent coeliac serological tests (antigliadins, transglutaminase and endomysium antibodies) and HLA-DQ typing. Small intestinal biopsy was performed when any of coeliac serological tests was positive. On the other hand, 184 patients with coeliac disease were subjected to thyroid biochemical (thyroid stimulating hormone and free thyroxine) and thyroid serological tests (thyroglobulin and thyroid peroxidase antibodies). RESULTS: Of 104 patients with Hashimoto's thyroiditis, sixteen (15%) were positive for coeliac serology and five patients with documented villous atrophy were diagnosed with coeliac disease (4.8%; 95% CI 0.7-8.9). HLA-DQ2 (and/or -DQ8) was present in all the five and 53 patients with Hashimoto's thyroiditis (50%; 95% CI 43-62). Of 184 patients with coeliac disease, 39 (21%) were positive for thyroid serology. Based on thyroid biochemistry, the 39 patients were subclassified into euthyroidism in ten (5%; 95% CI 2-9), subclinical hypothyroidism in seven (3.8%; 95% CI 1.8-7.6), and overt hypothyroidism (Hashimoto's thyroiditis) in 22 (12%; 95% CI 8-16). Moreover, four patients with coeliac disease had Graves' disease (2%; 95% CI 0.8-5) and one patient had post-partum thyroiditis. CONCLUSION: The data from a Dutch population confirm the association between Hashimoto's thyroiditis and coeliac disease. Screening patients with Hashimoto's thyroiditis for coeliac disease and vice versa is recommended.

Disentangling women's responses on complex dietary intake patterns from an Indian cross-sectional survey: a latent class analysis.

OBJECTIVE: To investigate the degree of individual heterogeneity related to complex dietary behaviour and to further examine the associations of different dietary compositions with selected characteristics. DESIGN: Latent class analysis was applied to data from the recent cross-sectional National Family Health Survey that collected information on the intake frequency of selected foods. Different responses regarding intake frequency were condensed into a set of five meaningful latent clusters representing different dietary patterns and these clusters were then labelled based on the reported degree of diet mixing. SETTING: Indian states. Subjects In total, 90,180 women aged 15-49 years. RESULTS: Three clusters were predominantly non-vegetarian and two were vegetarian. A very high or high mixed-diet pattern was observed particularly in the southern and a few north-eastern states. Many women in the very high mixed-diet cluster consumed mostly non-green/leafy vegetables on a daily basis, and fruits and other non-vegetarian diet on a weekly basis. In contrast, those in the low mixed-diet cluster consumed more than three-fifths of the major vegetarian diet ingredients alone on a daily basis. The affluent group that represented the low mixed-diet cluster were primarily vegetarians and those who represented the very high mixed-diet cluster were mostly non-vegetarians. The significant interrelationships of different characteristics highlight not only socio-economic, spatial and cultural disparities related to dietary practices, but also the substantial heterogeneity in diet mixing behaviour. CONCLUSIONS: The results of this study confirmed our hypothesis of heterogeneous dietary behaviour of Indian women and yielded useful policy-oriented results which might be difficult to establish otherwise.

Erythrocyte aging: a more than superficial resemblance to apoptosis?

In physiological circumstances, erythrocyte aging leads to binding of autologous IgG followed by recognition and removal through phagocytosis, mainly by Kupffer cells in the liver. This process is triggered by the appearance of a senescent erythrocyte-specific antigen. The functional and structural characteristics of senescent erythrocytes strongly suggest that this antigen originates on band 3, probably by calcium-induced proteolysis. Generation of vesicles enriched in denatured hemoglobin is an integral part of the erythrocyte aging process. These vesicles are also removed by Kupffer cells, with a major role for exposure of phosphatidylserine. Moreover, senescent erythrocyte-specific antigens are present on vesicles. Thus, vesicles and senescent erythrocytes may be recognized and removed through the same signals. These and other, recent data support the theory that erythrocyte aging is a form of apoptosis that is concentrated in the cell membrane, and provide the context for future studies on initiation and regulation of the erythrocyte aging process. Insight into the normal aging mechanism is essential for understanding the fate of erythrocytes in pathological circumstances and the survival of donor erythrocytes after transfusion.

Clinically relevant anterograde amnesia and its relationship with blood levels of benzodiazepines in suicide attempters who took an overdose.

The relationship between anterograde amnesia, sedation and plasma levels of benzodiazepines was studied prospectively in a group of 24 patients who took an overdose of benzodiazepines. Patients were tested on two sequential days after having taken an overdose. Anterograde amnesia was tested by using a verbal recall test and a photo recognition test. Sedation was scored on a visual analogue scale (VAS) by the patient and the interviewer. The concentration of benzodiazepines in plasma was measured by using a radioreceptor assay that adds benzodiazepines and their active metabolites. The cumulative amount of benzodiazepines was expressed as diazepam equivalents (DZE). Diazepam equivalents determined by this radioreceptor assay were significantly higher on the first day than on the second day. Ratings on the verbal recall test were significantly lower on the first day than on the second day. There was a significant relation between decrease of diazepam equivalents and increase of verbal recall: more than 30% of increase of verbal recall was explained by decrease of diazepam equivalents. There was not a strong relation between decrease of diazepam equivalents and reduction of level of sedation as scored by the patients. There was almost no relation between decrease of diazepam equivalents and reduction of level of sedation as scored by the interviewer. No relation was found between verbal recall, sedation and diazepam equivalents. There was no relation between diazepam equivalents and photo recognition. It was concluded that anterograde amnesia was strongly associated with benzodiazepines in patients who take benzodiazepines in an overdose. Sedation does not predict the degree of anterograde amnesia.

Liver Kupffer cells rapidly remove red blood cell-derived vesicles from the circulation by scavenger receptors.

Previous studies have shown that during the lifespan of red blood cells (RBCs) 20% of hemoglobin is lost by shedding of hemoglobin-containing vesicles. However, the fate of these vesicles is unknown. To study this fate we used a rat model, after having established that rat RBCs lose hemoglobin in the same way as human RBCs, and that RBC-derived vesicles are preferentially labeled by Na2(51) CrO4. Such labeled vesicles were injected into recipient rats. Within 5 minutes, 80% of the radioactivity was cleared from the circulation with a concomitant uptake by the liver of 55% of the injected dose. After 30 minutes, Kupffer cells contained considerable amounts of hemoglobin and were shown to be responsible for 92% of the liver uptake. Vesicle clearance from the blood as well as liver uptake were significantly inhibited by preinjection of the scavenger-receptor ligands polyinosinic acid and phosphatidylserine. We conclude that in rats Kupffer cells rapidly remove RBC-derived vesicles from the circulation, mainly by scavenger receptors. The same mechanism is likely to be responsible for the elimination of human RBC vesicles, thereby constituting an important pathway for the breakdown of RBCs in humans.

Compression of women's reproductive spans in Andhra Pradesh, India.

CONTEXT: The total fertility rate in Andhra Pradesh, India, has recently decreased to near-replacement level; however, the reasons for the fertility decline are unknown. METHODS: Data from the second round of the National Family Health Survey were used to examine the reproductive span-the duration between first marriage and menopause or sterilization-among 4,032 ever-married women aged 15-49 living in Andhra Pradesh in 1998-1999. RESULTS: Between 1992-1993 and 1998-1999, the median age at which women married remained at 15.1, whereas the age at which they adopted sterilization decreased from 24.5 to 23.6. In life-table analyses, reproductive spans of successive cohorts of women decreased-from 22 years among those who married during the 1960s to 15 years among those who married in the 1970s, 10 years among those who married in the 1980s and five years among those who married in 1990-1996. Proportional hazards regression analyses that controlled for demographic and social characteristics, as well as reproductive attitudes, confirmed this cohort effect (hazard ratios, 1.5-2.6). CONCLUSIONS: These findings suggest that women are making the decision to end childbearing faster than older generations did. The gradual compression in reproductive spans is attributable mainly to sterilization acceptance among younger women.