A Theoretical Framework to Derive Simple, Firing-Rate-Dependent Mathematical Models of Synaptic Plasticity

Synaptic plasticity serves as an essential mechanism underlying cognitive processes as learning and memory. For a better understanding detailed theoretical models combine experimental underpinnings of synaptic plasticity and match experimental results. However, these models are mathematically complex impeding the comprehensive investigation of their link to cognitive processes generally executed on the neuronal network level. Here, we derive a mathematical framework enabling the simplification of such detailed models of synaptic plasticity facilitating further mathematical analyses. By this framework we obtain a compact, firing-rate-dependent mathematical formulation, which includes the essential dynamics of the detailed model and, thus, of experimentally verified properties of synaptic plasticity. Amongst others, by testing our framework by abstracting the dynamics of two well-established calcium-dependent synaptic plasticity models, we derived that the synaptic changes depend on the square of the presynaptic firing rate, which is in contrast to previous assumptions. Thus, the here-presented framework enables the derivation of biologically plausible but simple mathematical models of synaptic plasticity allowing to analyze the underlying dependencies of synaptic dynamics from neuronal properties such as the firing rate and to investigate their implications in complex neuronal networks

Time Trends and Income Inequalities in Cancer Incidence and Cancer-Free Life Expectancy – a Cancer Site-Specific Analysis of German Health Insurance Data

Cancer represents a major burden of morbidity and mortality globally. So far, however, little is known on time trends and inequalities in the lengths of life spent free of any cancer. This study steps into this gap by analyzing time trends and income inequalities in cancer-free life expectancy (CFLE). For this retrospective cohort study, data of a large German health insurer were used (N = 3,405,673individuals, 2006–2018). Income inequalities were assessed using individual income (<60% of German average income (GAI) and ≥60% of GAI). Trends in incidence risks were analysed employing proportional-hazard regression models by splitting the observation time into three periods of 52 months. Trends in CFLE in total and for the most common site-specific cancers were calculated based on multiple decrement life tables. Incidence rates declined in almost all cancers and CFLE increased substantially over time (49.1 (95% CI 48.8-49.4) to 51.9 (95% CI 51.6-52.2) years for men, 53.1 (95% CI 52.7-53.5) to 55.4 (95% CI 55.1-55.8) years for women at age 20 for total cancer) and income groups. Considerable income inequalities in cancer risks were evident in both sexes, but were more pronounced in men (total cancer HR 0.86 (95% CI 0.85-0.87)), with higher-income individuals having lower risks. The highest income inequalities were found in colon (HR 0.90 (95% CI 0.87-0.93)), stomach (HR 0.78 (95% CI 0.73-0.84)), and lung cancer (HR 0.58 (95% CI 0.56-0.60)) in men. A reverse gradient was found for skin (HR 1.39 (95% CI 1.30-1.47) men; HR 1.27 (95% CI 1.20-1.35) women) and prostate cancer (HR 1.13 (95% CI 1.11-1.15)). The proportion of CFLE in total life expectancy declined for lung, skin and cervical cancer in women, indicating a relative shortening of lifetime spent cancer-free. In contrast, increasing proportions were found in breast and prostate cancer. To our knowledge, this is the first study analysing trends and income inequalities in CFLE. The life span free of cancer increased clearly over time. However, not all cancer types contributed equally to this positive development. Income inequalities persisted or tended to widen, which underlines the need for increased public health efforts in socioeconomically vulnerable groupsPeer Reviewe

Socioeconomic differences in limited lung function: a cross-sectional study of middle-aged and older adults in Germany

Limited lung function represents a serious health impairment. However, studies investigating social inequalities in limited lung function are rare. Thus, the current study investigates which socioeconomic groups are the most affected by overall limited lung function and severely limited lung function. Methods: Data from the population-based German Aging Survey were used (N = 4472), with participants being 40 + years old. Lung function was assessed by the peak flow test. Education, income, and occupational prestige were used as socioeconomic indicators. Results: We found that overall limited lung function was highly prevalent across the whole sample, with about 33% (Women: 35%; Men: 30%) having overall limited lung function and 8% (Women: 7%; Men: 8%) having severely limited lung function. Socioeconomic differences in limited lung function emerged for all three indicators, education, income, and occupational prestige, in both men and women in single effect analyses. These differences persisted for occupational prestige and income when controlling for all indicators simultaneously. Results: Thus, overall and severely limited lung function are highly prevalent health conditions. Men and women with a low occupational position and those with low income are the most affected. Socioeconomic indicators cannot be used interchangeably when studying health inequalities in lung functioning. Occupational hazards and physical working conditions are likely to constitute major risks of health inequalities in limited lung functioning and should be investigated as such by future studies

Estimating trends in working life expectancy based on health insurance data from Germany – Challenges and advantages

Against the backdrop of population aging and growing strain on pension systems, monitoring the development of Working Life Expectancy (WLE) is vital to assess whether the policies taken are effective. This is the first study investigating time trends and educational inequalities in WLE based on German health insurance data. The analyses are based on the data of the AOK Lower Saxony (N = 3,347,912) covering three time periods (2006-08, 2011-13, and 2016-18). WLE is defined as years spent in the labor force (i.e. in employment and unemployment) and was calculated for each age between 18 and 69 years for the three periods to depict changes over time using multistate life table analysis. Educational inequalities in 2011-13 are reported for two educational levels (8–11 years and 12–13 years of schooling). WLE increased in both sexes with increases being stronger among women. This holds irrespective of whether WLE at age 18 (35.8–38.3 years in men, 27.5–34.0 years in women) or the older working-age (e.g. at age 50 10.2–11.7 years in men, 7.8–10.5 years in men) is considered. Among women at all ages and men from their mid-20s onwards, WLE was higher among higher-educated individuals. Inequalities were most pronounced among women (e.g. Δ3.1 years in women, Δ1.3 years in men at age 50). The study supports previous research indicating that measures to extend working life are effective, but that noticeable inequalities in WLE exist. Health insurance data represent a valuable source for such research that has so far remained untapped. The data provide a suitable basis to investigate trends and inequalities in WLE. Future research should build on the strengths of the data by broadening the research towards a more comprehensive analysis of the development of WLE from a health perspective.Peer Reviewe

Wie hat sich die Lebenserwartung ohne funktionelle Einschränkungen in Deutschland entwickelt? Eine Analyse mit Daten des Deutschen Alterssurveys (DEAS)

Der langfristige Anstieg der Lebenserwartung wirft die Frage auf, ob die gewonnene Lebenszeit mit einer Verlängerung der Jahre ohne gesundheitliche Einschränkungen einhergeht. Die Studie untersucht, wie sich die Lebenserwartung ohne funktionelle und Mobilitätseinschränkungen ab dem Alter 46 und 65 Jahre sowie ihre Anteile an der Restlebenserwartung seit 2008 verändert haben. Methode: Wir analysieren Daten des Deutschen Alterssurveys der Wellen 2008, 2014 und 2020/2021. Die Lebenserwartung ohne funktionelle Einschränkungen (Disability Free Life Expectancy - DFLE) wurde mit der Sullivan-Methode berechnet. Untersucht wurden starke funktionelle Einschränkungen mit dem "Global Activity Limitation Indicator" (GALI) und Einschränkungen der Mobilität (Treppensteigen, mehr als 1 km Gehen). Ergebnisse: Kompression der Morbidität beim GALI ist bei 46- und 65-jährigen Männern seit 2014 zu beobachten, bei gleichaltrigen Frauen dagegen nicht. Bei der Mobilität zeigen 46- und 65-jährige Männer Tendenzen zur Kompression beim Treppensteigen und 46-jährige Männer beim Gehen von mehr als 1 km seit 2014. Die Werte für Frauen stagnieren für die beiden erstgenannten Indikatoren, aber nicht für 46-jährige Frauen beim Gehen von mehr als 1 km seit 2014. Diskussion: Unsere Analysen zeigen je nach Indikator, Alter und Geschlecht unterschiedliche Trends der DFLE und lassen keine eindeutige Antwort auf die Frage nach Morbiditätskompression oder -expansion zu. Kompression der Morbidität sehen wir eher bei Männern, Tendenzen der Stagnation oder Expansion dagegen eher bei Frauen. Diese Resultate signalisieren Herausforderungen in der Erhaltung der funktionellen Gesundheit vor allem bei Frauen und weisen auf die Notwendigkeit gezielter Interventionen hin, um die Lebensqualität und die gesunde Lebenserwartung zu verbessern.Introduction: The long-term increase in life expectancy raises the question of whether the increased life expectancy is accompanied by an extension of years without health limitations. The study analyzes how life expectancy without functional and mobility limitations from the ages of 46 and 65 and their proportions of remaining life expectancy have changed since 2008. Methods: We analyze data from the German Ageing Survey of the 2008, 2014, and 2020/21 waves. Life expectancy without functional limitations (Disability-free life expectancy - DFLE) was calculated using the Sullivan method. Severe functional limitations (using the Global Activity Limitation Indicator - GALI) and mobility limitations (climbing stairs, walking more than 1 km) were examined. Results: Compression of morbidity in the GALI has been observed in 46- and 65-year-old men since 2014, but not in women of the same age. In terms of mobility, 46- and 65-year-old men show trends towards compression when climbing stairs and 46-year-old men when walking more than 1 km since 2014. The values for women have stagnated for the first two indicators mentioned, but not for 46-year-old women since 2014 when walking more than 1 km. Discussion: Our analyses show different trends in DFLE depending on the indicator, age, and gender and do not allow a clear answer to the question of morbidity¬compression or expansion. We tend to see morbidity compression in men, whereas trends of stagnation or expansion tend to be seen in women. These results signal challenges in maintaining functional health, especially in women, and point to the need for targeted interventions to improve quality of life and healthy life expectancy

26th Annual Computational Neuroscience Meeting (CNS*2017): Part 3 - Meeting Abstracts - Antwerp, Belgium. 15–20 July 2017

This work was produced as part of the activities of FAPESP Research,\ud Disseminations and Innovation Center for Neuromathematics (grant\ud 2013/07699-0, S. Paulo Research Foundation). NLK is supported by a\ud FAPESP postdoctoral fellowship (grant 2016/03855-5). ACR is partially\ud supported by a CNPq fellowship (grant 306251/2014-0)

Healthy enough to work up to age 67 and beyond? A longitudinal population-based study on time trends in working life expectancy free of cardiovascular diseases based on German health insurance data

Background Due to the rising life expectancy in Western countries, the discussion about the increase in the retirement age is becoming more important. However, the prolongation of working lives cannot be implemented successfully without considering the health status of the (potential) employees. In this study, time trends in working life expectancy (WLE) free of widespread cardiovascular diseases (CVD) as well as the proportion of CVD-free working life years are reported.Methods Claims data from a German statutory health insurance provider is used to analyse CVD-free WLE. Three periods were defined to assess time trends: 2006–2008 (n=2 075 248), 2011–2013 (n=2 302 127) and 2016–2018 (n=2 579 985). Based on transition rates between the states labour force, non-labour force, CVD and death, CVD-free years spent in the labour force were estimated for each age using multistate life table analyses.Results The length of CVD-free WLE increased over time. This increase was stronger in women than in men (+6.4 years vs +2.4 years at age 18). Given the increase in total WLE of the study population, the proportion of CVD-free WLE in total WLE remained stable over time.Conclusions The results show that working life years free of CVD increased strongly over the last 13 years and can keep pace with the increase in the length of working lives. Healthier working conditions as well as more efforts in promoting healthy nutrition and less sedentary behaviour could help to further reduce the incidence of CVD and thus contribute to longer healthy working lives

Income inequalities in stroke incidence and mortality: Trends in stroke-free and stroke-affected life years based on German health insurance data.

BACKGROUND:Due to substantial improvements in prevention and therapy, stroke incidence and mortality rates have decreased during the last decades, but evidence is still lacking on whether all socioeconomic groups benefited equally and how the length of life affected by stroke developed over time. Our study investigates time trends in stroke-free life years and life years affected by stroke. Special emphasis is given to the question whether trends differ between income groups, leading to decreasing or increasing social inequalities. METHODS:The analyses are based on claims data of a German statutory health insurance company of the two time periods 2006-2008 and 2014-2016. Income inequalities and time trends in incidence and mortality risks were estimated using multistate survival models. Trends in stroke-free life years and life years affected by stroke are analysed separately for income groups by applying multistate life table analyses. RESULTS:Stroke incidence and mortality risks decreased in men and women in all income groups. While stroke-free lifetime could be gained in men having higher incomes, improvements in mortality counterbalanced decreasing incidences, leading to increases in life years affected by stroke among men of the lower and higher income group. Among women, no significant changes in life years could be observed. CONCLUSIONS:Changes in stroke-affected life years occur among men in all income groups, but are more pronounced in the higher income group. However, irrespective of the income group the proportion of stroke-affected life years remains quite stable over time, pointing towards constant inequalities. Further research is needed on whether impairments due to stroke reduced over time and whether all socioeconomic groups are affected equally

Compression, expansion, or maybe both? Growing inequalities in lung cancer in Germany.

BackgroundLung Cancer (LC) is one of the most common malign diseases worldwide. So far, it is unclear if the development of LC incidence and mortality leads to morbidity compression or expansion and whether these developments differ by socioeconomic characteristics. This study analyses time trends in social and gender inequalities in life years with and without LC in Germany.MethodsThe study is based on data of a large German statutory health insurance provider (N = 2,511,790). Incidence and mortality risks were estimated from multistate survival models. Trends in life years with and without LC were analysed using multistate life table analyses. All analyses were performed separately for gender, time period (2006-2009 and 2014-2017), and income group (ResultsAmong men, declining LC incidence rates resulted in gains of life years free of LC and declining LC- affected life years and led to a relative compression, which was strongest in men with higher incomes. Among women, a clear increase in life years with LC led to an expansion of the lifespan affected by LC. This expansion was mainly driven by increasing incidence rates in women with low incomes. Overall, income inequalities in LC increased in both genders.ConclusionsOur analyses reveal that developments in the length of life affected by LC differed substantially by gender and income and led to widening health inequalities over time. Public health efforts should mainly focus on vulnerable groups to reduce the persisting social inequalities in LC