Social Differences in Infant Mortality in 19th Century Rostock. A Demographic Analysis Based on Church Records

Der Originalbeitrag in deutscher Sprache ist verfügbar unter: Bd. 40 (2015): Ausgewählte deutsche Beiträge.  The article examines the historical development of infant mortality in the Hanseatic city of Rostock, with a special focus on the question of how socio-economic factors influenced infant mortality in the early 19th century. Compared with the rest of Germany, the city exhibited an exceedingly low infant mortality level, in particular in the first third of the century. Our analyses show that the occupation of the father had a significant influence on the survival probability of a child in the first year of life in the early 19th century. Newborn children of fathers in lower ranked occupations exhibited a greater mortality risk in the first year of life than the offspring of fathers with occupations of higher status. The analyses are based on the registries of burials and baptisms of St. James’s Church (Jakobikirche) in Rostock, which are largely preserved and much of which has been digitalised. Based on these individual data, this is the first event history analysis model conducted in the context of infant mortality in a German city in the 19th century. This article is also the first to reveal Rostock infant mortality rates for the entire 19th century according to sex, thus closing two research gaps.The article examines the historical development of infant mortality in the Hanseatic city of Rostock, with a special focus on the question of how socio-economic factors influenced infant mortality in the early 19th century. Compared with the rest of Germany, the city exhibited an exceedingly low infant mortality level, in particular in the first third of the century. Our analyses show that the occupation of the father had a significant influence on the survival probability of a child in the first year of life in the early 19th century. Newborn children of fathers in lower ranked occupations exhibited a greater mortality risk in the first year of life than the offspring of fathers with occupations of higher status. The analyses are based on the registries of burials and baptisms of St. James’s Church (Jakobikirche) in Rostock, which are largely preserved and much of which has been digitalised. Based on these individual data, this is the first event history analysis model conducted in the context of infant mortality in a German city in the 19th century. This article is also the first to reveal Rostock infant mortality rates for the entire 19th century according to sex, thus closing two research gaps

Soziale Unterschiede in der Säuglingssterblichkeit in Rostock im 19. Jahrhundert

Der Beitrag untersucht die historische Entwicklung der Säuglingssterblichkeit in der Hansestadt Rostock und widmet sich im Speziellen der Frage, inwieweit sozioökonomische Faktoren die Höhe der Säuglingssterblichkeit im frühen 19. Jahrhundert beeinflussten. Es lässt sich für die Stadt ein im deutschlandweiten Vergleich äußerst niedriges Säuglingssterblichkeitsniveau feststellen, besonders für das erste Drittel des Jahrhunderts. Dabei kann ein signifikanter Einfluss der beruflichen Schicht des Vaters auf die Überlebenschancen des Kindes im ersten Lebensjahr für das frühe 19. Jahrhundert nachgewiesen werden: Neugeborene von beruflich schlechter gestellten Vätern weisen ein größeres Sterberisiko im ersten Lebensjahr auf als die Nachkommen beruflich besser gestellter Väter. Als Datengrundlage dienen die Beerdigungs- und Taufregister der Rostocker Jakobikirche, welche weitgehend erhalten und zu einem großen Teil digitalisiert sind. Auf der Basis dieser Individualdaten wird erstmals ein Ereignisdatenanalysemodell im Zusammenhang mit der Säuglingssterblichkeit in einer deutschen Stadt im 19. Jahrhundert untersucht. Des Weiteren zeigt dieser Beitrag erstmals die Säuglingssterbewahrscheinlichkeit der Stadt Rostock für das gesamte 19. Jahrhundert nach Geschlecht und schließt damit in zweifacher Hinsicht eine Forschungslücke.The English translation of this article is available in Vol 40, No 2 (2015).Der Beitrag untersucht die historische Entwicklung der Säuglingssterblichkeit in der Hansestadt Rostock und widmet sich im Speziellen der Frage, inwieweit sozioökonomische Faktoren die Höhe der Säuglingssterblichkeit im frühen 19. Jahrhundert beeinflussten. Es lässt sich für die Stadt ein im deutschlandweiten Vergleich äußerst niedriges Säuglingssterblichkeitsniveau feststellen, besonders für das erste Drittel des Jahrhunderts. Dabei kann ein signifikanter Einfluss der beruflichen Schicht des Vaters auf die Überlebenschancen des Kindes im ersten Lebensjahr für das frühe 19. Jahrhundert nachgewiesen werden: Neugeborene von beruflich schlechter gestellten Vätern weisen ein größeres Sterberisiko im ersten Lebensjahr auf als die Nachkommen beruflich besser gestellter Väter. Als Datengrundlage dienen die Beerdigungs- und Taufregister der Rostocker Jakobikirche, welche weitgehend erhalten und zu einem großen Teil digitalisiert sind. Auf der Basis dieser Individualdaten wird erstmals ein Ereignisdatenanalysemodell im Zusammenhang mit der Säuglingssterblichkeit in einer deutschen Stadt im 19. Jahrhundert untersucht. Des Weiteren zeigt dieser Beitrag erstmals die Säuglingssterbewahrscheinlichkeit der Stadt Rostock für das gesamte 19. Jahrhundert nach Geschlecht und schließt damit in zweifacher Hinsicht eine Forschungslücke

Neurite-Enriched MicroRNA-218 Stimulates Translation of the GluA2 Subunit and Increases Excitatory Synaptic Strength

Local control of protein translation is a fundamental process for the regulation of synaptic plasticity. It has been demonstrated that the local protein synthesis occurring in axons and dendrites can be shaped by numerous mechanisms, including miRNA-mediated regulation. However, several aspects underlying this regulatory process have not been elucidated yet. Here, we analyze the differential miRNA profile in cell bodies and neurites of primary hippocampal neurons and find an enrichment of the precursor and mature forms of miR-218 in the neuritic projections. We show that miR-218 abundance is regulated during hippocampal development and by chronic silencing or activation of neuronal network. Overexpression and knockdown of miR-218 demonstrated that miR-218 targets the mRNA encoding the GluA2 subunit of AMPA receptors and modulates its expression. At the functional level, miR-218 overexpression increases glutamatergic synaptic transmission at both single neuron and network levels. Our data demonstrate that miR-218 may play a key role in the regulation of AMPA-mediated excitatory transmission and in the homeostatic regulation of synaptic plasticity

Quantitative comparison between in vivo DNA adduct formation from exposure to selected DNA-reactive carcinogens, natural background levels of DNA adduct formation and tumour incidence in rodent bioassays

This study aimed at quantitatively comparing the occurrence/formation of DNA adducts with the carcinogenicity induced by a selection of DNA-reactive genotoxic carcinogens. Contrary to previous efforts, we used a very uniform set of data, limited to in vivo rat liver studies in order to investigate whether a correlation can be obtained, using a benchmark dose (BMD) approach. Dose-response data on both carcinogenicity and in vivo DNA adduct formation were available for six compounds, i.e. 2-acetylaminofluorene, aflatoxin B1, methyleugenol, safrole, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline and tamoxifen. BMD10 values for liver carcinogenicity were calculated using the US Environmental Protection Agency BMD software. DNA adduct levels at this dose were extrapolated assuming linearity of the DNA adduct dose response. In addition, the levels of DNA adducts at the BMD10 were compared to available data on endogenous background DNA damage in the target organ. Although for an individual carcinogen the tumour response increases when adduct levels increase, our results demonstrate that when comparing different carcinogens, no quantitative correlation exists between the level of DNA adduct formation and carcinogenicity. These data confirm that the quantity of DNA adducts formed by a DNA-reactive compound is not a carcinogenicity predictor but that other factors such as type of adduct and mutagenic potential may be equally relevant. Moreover, comparison to background DNA damage supports the notion that the mere occurrence of DNA adducts above or below the level of endogenous DNA damage is neither correlated to development of cancer. These data strongly emphasise the need to apply the mode of action framework to understand the contribution of other biological effect markers playing a role in carcinogenicit

In vivo validation of DNA adduct formation by estragole in rats predicted by physiologically based biodynamic modelling

Estragole is a naturally occurring food-borne genotoxic compound found in a variety of food sources, including spices and herbs. This results in human exposure to estragole via the regular diet. The objective of this study was to quantify the dose-dependent estragole-DNA adduct formation in rat liver and the urinary excretion of 1'-hydroxyestragole glucuronide in order to validate our recently developed physiologically based biodynamic (PBBD) model. Groups of male outbred Sprague Dawley rats (n = 10, per group) were administered estragole once by oral gavage at dose levels of 0 (vehicle control), 5, 30, 75, 150, and 300mg estragole/kg bw and sacrificed after 48h. Liver, kidney and lungs were analysed for DNA adducts by LC-MS/MS. Results obtained revealed a dose-dependent increase in DNA adduct formation in the liver. In lungs and kidneys DNA adducts were detected at lower levels than in the liver confirming the occurrence of DNA adducts preferably in the target organ, the liver. The results obtained showed that the PBBD model predictions for both urinary excretion of 1'-hydroxyestragole glucuronide and the guanosine adduct formation in the liver were comparable within less than an order of magnitude to the values actually observed in vivo. The PBBD model was refined using liver zonation to investigate whether its predictive potential could be further improved. The results obtained provide the first data set available on estragole-DNA adduct formation in rats and confirm their occurrence in metabolically active tissues, i.e. liver, lung and kidney, while the significantly higher levels found in liver are in accordance with the liver as the target organ for carcinogenicity. This opens the way towards future modelling of dose-dependent estragole liver DNA adduct formation in huma

Evaluation of Human Interindividual Variation in Bioactivation of Estragole Using Physiologically Based Biokinetic Modeling

The present study investigates interindividual variation in liver levels of the proximate carcinogenic metabolite of estragole, 1′-hydroxyestragole, due to variation in two key metabolic reactions involved in the formation and detoxification of this metabolite, namely 1′-hydroxylation of estragole and oxidation of 1′-hydroxyestragole. Formation of 1′-hydroxyestragole is predominantly catalyzed by P450 1A2, 2A6, and 2E1, and results of the present study support that oxidation of 1′-hydroxyestragole is catalyzed by 17β-hydroxysteroid dehydrogenase type 2 (17β-HSD2). In a first approach, the study defines physiologically based biokinetic (PBBK) models for 14 individual human subjects, revealing a 1.8-fold interindividual variation in the area under the liver concentration-time curve (AUC) for 1′-hydroxyestragole within this group of human subjects. Variation in oxidation of 1′-hydroxyestragole by 17β-HSD2 was shown to result in larger effects than those caused by variation in P450 enzyme activity. In a second approach, a Monte Carlo simulation was performed to evaluate the extent of variation in liver levels of 1′-hydroxyestragole that could occur in the population as a whole. This analysis could be used to derive a chemical-specific adjustment factor (CSAF), which is defined as the 99th percentile divided by the 50th percentile of the predicted distribution of the AUC of 1′-hydroxyestragole in the liver. The CSAF was estimated to range between 1.6 and 4.0, depending on the level of variation that was taken into account for oxidation of 1′-hydroxyestragole. Comparison of the CSAF to the default uncertainty factor of 3.16 for human variability in biokinetics reveals that the default uncertainty factor adequately protects 99% of the populatio

Bevölkerungsprognose für Mecklenburg-Vorpommern auf Kreisebene bis zum Jahr 2030

"In order to make precise and forward-looking decisions in nearly all social fields, detailed information on the size and structure of prospective populations in specific regional areas is needed. For that purpose, this article will show how current trends of demographic parameters affect the development of the population in administrative districts of the federal state of Mecklenburg-Western Pomerania until 2030. Based upon population data from 1982 until 2005, provided by the Federal State Agency of Statistics of Mecklenburg-Western Pomerania, this paper presents a projection of the population as well as the aging and the sex proportion of the federal state until 2030. The development of off-county cities, counties and the whole federal state were calculated by applying the cohort-survival- method and prediction module of the Federal State Agency of Statistics of Mecklenburg-Western Pomerania. The fertility and migration assumptions chosen, are following the assumptions of the last coordinated population projection of the Federal State Agency of Statistics of Mecklenburg-Western Pomerania (2007). The mortality assumptions enter the analysis analogously to the county- and sex-specific projections of life expectancy, as they are used within the Lee-Carter-method (1982 - 2005). The results show a population decrease of about 180.000 inhabitants until 2030 for the entire federal state with strongest population loss until 2012. In the following years the outflow of people strongly decreases, because cohorts in migration relevant ages are missing. The population development of the six off-county cities is rather different. Rostock and Greifswald will note a population increase until 2030, whereas the number of residents in Wismar and Stralsund will be stable. Schwerin and Neubrandenburg will lose residents. Every county will diminish enormously; except Bad Doberan which has to count on a population increase, while Uecker-Randow and Demmin will lose most inhabitants. In the forthcoming years the counties will not only be shrinking, but they will also age above average. The mean age of all counties will grow by 10.5 years until 2030. In the cities it will increase by 4.4 years and for entire Mecklenburg-Western Pomerania it will increase by 8.2 years. Counties with positive population development will age most slightly. The absolute quantity as well as the relative proportion of seniors (aged 64+) and oldest old (aged 79+) will grow in all counties. A similar picture can be seen in the cities, where the absolute quantities of oldest old and seniors will also increase, wheras the relative proportions are smaller. In 2030 the proportion of seniors of all cities will be below the federal state mean, except for Neubrandenburg. Overall, inhabitants aged 50 and older will increase, whilst persons in reproductive ages between 15 and 49 years will exhibit a declining proportion of population. Hence, the birth deficit will be further intensified. Moreover, a high predominance of men within the younger population could be discovered for the 1990s. This predominance of men will be put forward as a cohort effect in older age groups during the following years. At county level it can be shown, that the projected values for the cities comparatively turn out to be more positive, whilst the projections for some counties give a more pessimistic outlook. The latter finding has to be traced back to the migration assumptions. This projection is on par with results of previous projections which also showed shrinkage and aging trends for Mecklenburg-Western Pomerania. Updated federal state population quantities reflect both processes as well. The projected, further increasing absolute quantities of older and the decreasing quantities of young people in urban and less populated regions, imply an urgent need for action from political and economical decision makers. An age-appropriate infrastructure as well as a good performing care- and health system for the growing number of further aging persons are required to absorb the ongoing and projected trends. Political decisions have especially to be made for sparsely populated regions to maintain security of supply and infrastructure." (author's abstract

Use of Physiologically Based Biokinetic (PBBK) Modeling to Study Estragole Bioactivation and Detoxification in Humans as Compared with Male Rats

The extent of bioactivation of the herbal constituent estragole to its ultimate carcinogenic metabolite 1′-sulfooxyestragole depends on the relative levels of bioactivation and detoxification pathways. The present study investigated the kinetics of the metabolic reactions of both estragole and its proximate carcinogenic metabolite 1′-hydroxyestragole in humans in incubations with relevant tissue fractions. Based on the kinetic data obtained a physiologically based biokinetic (PBBK) model for estragole in human was defined to predict the relative extent of bioactivation and detoxification at different dose levels of estragole. The outcomes of the model were subsequently compared with those previously predicted by a PBBK model for estragole in male rat to evaluate the occurrence of species differences in metabolic activation. The results obtained reveal that formation of 1′-oxoestragole, which represents a minor metabolic route for 1′-hydroxyestragole in rat, is the main detoxification pathway of 1′-hydroxyestragole in humans. Due to a high level of this 1′-hydroxyestragole oxidation pathway in human liver, the predicted species differences in formation of 1′-sulfooxyestragole remain relatively low, with the predicted formation of 1′-sulfooxyestragole being twofold higher in human compared with male rat, even though the formation of its precursor 1′-hydroxyestragole was predicted to be fourfold higher in human. Overall, it is concluded that in spite of significant differences in the relative extent of different metabolic pathways between human and male rat there is a minor influence of species differences on the ultimate overall bioactivation of estragole to 1′-sulfooxyestragol

Exposure assessment of process-related contaminants in food by biomarker monitoring

Exposure assessment is a fundamental part of the risk assessment paradigm, but can often present a number of challenges and uncertainties. This is especially the case for process contaminants formed during the processing, e.g. heating of food, since they are in part highly reactive and/or volatile, thus making exposure assessment by analysing contents in food unreliable. New approaches are therefore required to accurately assess consumer exposure and thus better inform the risk assessment. Such novel approaches may include the use of biomarkers, physiologically based kinetic (PBK) modelling-facilitated reverse dosimetry, and/or duplicate diet studies. This review focuses on the state of the art with respect to the use of biomarkers of exposure for the process contaminants acrylamide, 3-MCPD esters, glycidyl esters, furan and acrolein. From the overview presented, it becomes clear that the field of assessing human exposure to process-related contaminants in food by biomarker monitoring is promising and strongly developing. The current state of the art as well as the existing data gaps and challenges for the future were defined. They include (1) using PBK modelling and duplicate diet studies to establish, preferably in humans, correlations between external exposure and biomarkers; (2) elucidation of the possible endogenous formation of the process-related contaminants and the resulting biomarker levels; (3) the influence of inter-individual variations and how to include that in the biomarker-based exposure predictions; (4) the correction for confounding factors; (5) the value of the different biomarkers in relation to exposure scenario’s and risk assessment, and (6) the possibilities of novel methodologies. In spite of these challenges it can be concluded that biomarker-based exposure assessment provides a unique opportunity to more accurately assess consumer exposure to process-related contaminants in food and thus to better inform risk assessment