Risk adjustment in aging societies

Background In Switzerland, age is the predominant driver of solidarity transfers in risk adjustment (RA). Concerns have been voiced regarding growing imbalances in cost sharing between young and old insured due to demographic changes (larger fraction of elderly >65 years and rise in average age). Particularly young adults aged 19–25 with limited incomes have to shoulder increasing solidarity burdens. Between 1996 and 2011, monthly intergenerational solidarity payments for young adults have doubled from CHF 87 to CHF 182, which corresponds to the highest absolute transfer increase of all age groups. Results By constructing models for age-specific RA growth and for calculating the lifetime sum of RA transfers we investigated the causes and consequences of demographic changes on RA payments. The models suggest that the main driver for RA increases in the past was below average health care expenditure (HCE) growth in young adults, which was only half as high (average 2% per year) compared with older adults (average 4% per year). Shifts in age group distributions were only accountable for 2% of the CHF 95 rise in RA payments. Despite rising risk adjustment debts for young insured the balance of lifetime transfers remains positive as long as HCE growth rates are greater than the discount rate used in this model (3%). Moreover, the life-cycle model predicts that the lifetime rate of return on RA payments may even be further increased by demographic changes. Nevertheless, continued growth of RA contributions may overwhelm vulnerable age groups such as young adults. We therefore propose methods to limit the burden of social health insurance for specific age groups (e.g. young adults in Switzerland) by capping solidarity payments. Conclusions Taken together, our mathematical modelling framework helps to gain a better understanding of how demographic changes interact with risk adjustment and how redistribution of funds between age groups can be controlled without inducing further selection incentives. Those methods can help to construct more equitable systems of health financing in light of population aging.

Alpine lacustrine varved record reveals summer temperature as main control of glacier fluctuations over the past 2250 years

Glacier fluctuations are a key indicator of changing climate. Their reconstruction beyond historical times unravels glacier variability and its forcing factors on long time scales, which can considerably improve our understanding of the climate–glacier relationship. Here, we present a 2250-year-long reconstruction of particle-mass accumulation rates recorded in the lacustrine sediments of Lake Trüebsee (Central Swiss Alps) that are directly related to glacier extent, thus reflecting a continuous record of fluctuations of the upstream-located Titlis Glacier. Mass accumulation rate values show strong centennial to multi-centennial fluctuations and reveal 12 well-pronounced periods of enhanced values corresponding to times of maximum extent of the neighboring Lower Grindelwald Glacier. This result supports previous studies of proglacial lake sediments that documented high mass accumulation rate values during glacier advances. The strong variability in the Lake Trüebsee mass accumulation rate record thus represents a highly sensitive paleoclimatic archive, which mirrors rapid and pronounced feedbacks of Titlis Glacier to climatic changes over the past 2250years. The comparison of our data with independent paleo-temperature reconstructions from tree rings suggests that variations in mean summer temperature were the primary driving factor of fluctuations of Titlis Glacier. Also, advances of Titlis Glacier occurred during the grand solar minima (Dalton, Maunder, Spörer, Wolf) of the last millennium. This relation of glacier extent with summer temperature reveals strong evidence that the mass balance of this Alpine glacier is primarily controlled by the intensity of glacier melting during summer.

Simulating Carbon Stocks and Fluxes of an African Tropical Montane Forest with an Individual-Based Forest Model

Tropical forests are carbon-dense and highly productive ecosystems. Consequently, they play an important role in the global carbon cycle. In the present study we used an individual-based forest model (FORMIND) to analyze the carbon balances of a tropical forest. The main processes of this model are tree growth, mortality, regeneration, and competition. Model parameters were calibrated using forest inventory data from a tropical forest at Mt. Kilimanjaro. The simulation results showed that the model successfully reproduces important characteristics of tropical forests (aboveground biomass, stem size distribution and leaf area index). The estimated aboveground biomass (385 t/ha) is comparable to biomass values in the Amazon and other tropical forests in Africa. The simulated forest reveals a gross primary production of 24 tcha-1yr-1. Modeling above- and belowground carbon stocks, we analyzed the carbon balance of the investigated tropical forest. The simulated carbon balance of this old-growth forest is zero on average. This study provides an example of how forest models can be used in combination with forest inventory data to investigate forest structure and local carbon balances.

T Cell Motility as Modulator of Interactions with Dendritic Cells

It is well established that the balance of costimulatory and inhibitory signals during interactions with dendritic cells (DCs) determines T cell transition from a naïve to an activated or tolerant/anergic status. Although many of these molecular interactions are well reproduced in reductionist in vitro assays, the highly dynamic motility of naïve T cells in lymphoid tissue acts as an additional lever to fine-tune their activation threshold. T cell detachment from DCs providing suboptimal stimulation allows them to search for DCs with higher levels of stimulatory signals, while storing a transient memory of short encounters. In turn, adhesion of weakly reactive T cells to DCs presenting peptides presented on major histocompatibility complex with low affinity is prevented by lipid mediators. Finally, controlled recruitment of CD8(+) T cells to cognate DC-CD4(+) T cell clusters shapes memory T cell formation and the quality of the immune response. Dynamic physiological lymphocyte motility therefore constitutes a mechanism to mitigate low avidity T cell activation and to improve the search for "optimal" DCs, while contributing to peripheral tolerance induction in the absence of inflammation.

INVESTIGATIONS ON THE INTRACELLULAR LOCALIZATION OF PHOSPHATIDYLSERINE SYNTHASE FROM ESCHERICHIA COLI

Phosphatidylserine synthase catalyzes the committed step in the synthesis of the major lipid of Escherichia coli, phosphatidylethanolamine, and may be involved in regulating the balance of the zwitterionic and anionic phospholipids in the membrane. Unlike the other enzymes involved in the biosynthesis of phospholipids in E. coli, phosphatidylserine synthase is not membrane associated but seems to have a high affinity for the ribosomal fraction of cells broken by various methods. Investigations on the enzyme in cell free extracts using glycerol gradient centrifugation revealed that the binding of the synthase to ribosomes may be prevented by the presence of highly basic compounds such as spermidine and by the presence of detergent-lipid substrate micelles under assay conditions. Thus phosphatidylserine synthase may not be ribosome associated under physiological conditions but associated with its membrane bound substrate (Louie and Dowhan (1980) J. Biol. Chem. 255, 1124).^ In addition homogeneous enzyme shows many of the properties of a membrane associated protein. It binds nonionic detergent such as Triton X-100, which is also required during purification of the enzyme. Optimal catalytic activity is also dependent on micelle or surface bound substrate. Phosphatidylserine synthase has been synthesized in vitro using a coupled transcription-translation system dependent on the presence of the cloned structural gene. The translation product was found to preferentially associate with the ribosomal fraction even in the presence of added E. coli membranes. Preferential membrane binding could be induced if the membranes were supplemented with the lipid substrate CDP-diacylglycerol. Similar effects were obtained with the acidic lipids phosphatidylglycerol and cardiolipin. On the other hand the zwitterionic lipid phosphatidylethanolamine and the lipid product phosphatidylserine did not cause any detectable membrane association. These results are consistent with the enzyme recognizing membrane bound substrate (Carman and Dowhan (1979) J. Biol. Chem. 254, 8391) and with the lipid charge influencing membrane interaction.^ Phosphatidylserine synthase is at a branch point in lipid metabolism, which may determine the distribution of the zwitterionic and anionic phospholipids in the membrane. The results obtained here indicate phosphatidylserine synthase may play a significant role in membrane lipid biosynthesis by maintaining charge balance of the E. coli membrane. In determining the localization of phosphatidylserine synthase in vitro one may have a better understanding of its function and control in vivo and may also have a better understanding of its role in membrane assembly.^

A systematic review of literature to compare the fertility desires among HIV positive women and cancer survivors

Background. Decision-making on reproductive issues is influenced by an interplay of individual, familial, medical, religious and socio-cultural factors. Women with chronic medical illnesses such an HIV infection and cancers are often fraught with decisional conflicts about child-bearing. With increase in the incidence of these illnesses as well as improvement in survival rates, there is a need to pay due attention to the issue of reproductive decision-making. Examining the prevalence and determinants of fertility desires in the two groups in a comparative manner would help bring to light perception of the medical community and the society in general on the two illnesses and the issue of motherhood. ^ Methods. Systematic literature search was undertaken using databases such as MEDLINE (PubMED), MEDLINE (Ovid), PsycInfo and Web of Science. Articles published in English and English language abstracts for foreign articles were included. Studies that explore ‘fertility desires’ as the outcome variable were included. Quantitative studies which have assessed the prevalence of fertility desires as well as qualitative studies which have provided a descriptive understanding of factors governing reproductive desires were included in the review. ^ Results. A total of 34 articles (29 studies examining HIV and 5 studies examining cancer in relation to fertility desires). Variables such as age, stage of illness, support of spouse and family, perception of the medical community and one’s own view of motherhood were key determinants among both groups. ^ Conclusion. There is a need for uniform, systematic research in this field. It is important that health care workers acknowledge these decisional conflicts, include them as part of the medical care of these patients and provide guidance with the right balance of information, practicality and compassion.^

ECONOMIC ANALYSIS OF THE DEMAND FOR PRESCRIPTION MEDICINE IN THE UNITED STATES

The purpose of this study was to understand the role of principle economic, sociodemographic and health status factors in determining the likelihood and volume of prescription drug use. Econometric demand regression models were developed for this purpose. Ten explanatory variables were examined: family income, coinsurance rate, age, sex, race, household head education level, size of family, health status, number of medical visits, and type of provider seen during medical visits. The economic factors (family income and coinsurance) were given special emphasis in this study.^ The National Medical Care Utilization and Expenditure Survey (NMCUES) was the data source. The sample represented the civilian, noninstitutionalized residents of the United States in 1980. The sample method used in the survey was a stratified four-stage, area probability design. The sample was comprised of 6,600 households (17,123 individuals). The weighted sample provided the population estimates used in the analysis. Five repeated interviews were conducted with each household. The household survey provided detailed information on the United States health status, pattern of health care utilization, charges for services received, and methods of payments for 1980.^ The study provided evidence that economic factors influenced the use of prescription drugs, but the use was not highly responsive to family income and coinsurance for the levels examined. The elasticities for family income ranged from -.0002 to -.013 and coinsurance ranged from -.174 to -.108. Income has a greater influence on the likelihood of prescription drug use, and coinsurance rates had an impact on the amount spent on prescription drugs. The coinsurance effect was not examined for the likelihood of drug use due to limitations in the measurement of coinsurance. Health status appeared to overwhelm any effects which may be attributed to family income or coinsurance. The likelihood of prescription drug use was highly dependent on visits to medical providers. The volume of prescription drug use was highly dependent on the health status, age, and whether or not the individual saw a general practitioner. ^

The Rise and Fall of the Doctor-Patient Relationship

This talk will outline the history of the doctor-patient relationship in the West. It will touch briefly on medicine in Greek and Roman antiquity, using key texts from Hippocrates and Galen. It will also sketch the changing balance of the religious and the secular in medieval medicine. Finally, it will outline the rise of the modern personal doctor-patient relationship in the 18th century and analyze the chronic dissatisfaction that settled over relations between doctors and patients in the last quarter of the 20th century.

The role of municipalities in air toxics regulation: The Houston experience

The federal regulatory regime for addressing airborne toxic pollutants functions fairly well in most of the country. However, it has proved deficient in addressing local risk issues, especially in urban areas with densely concentrated sources. The problem is especially pronounced in Houston, which is home to one of the world's biggest petrochemical complexes and a major port, both located near a large metropolitan center. Despite the fact that local government's role in regulating air toxics is typically quite limited, from 2004-2009, the City of Houston implemented a novel municipality-based air toxics reduction strategy. The initiatives ranged from voluntary agreements to litigation and legislation. This case study considers why the city chose the policy tools it did, how the tools performed relative to the designers' intentions, and how the debate among actors with conflicting values and goals shaped the policy landscape. The city's unconventional approach to controlling hazardous air pollution has not yet been examined rigorously. The case study was developed through reviews of publicly available documents and quasi-public documents obtained through public record requests, as well as interviews with key informants. The informants represented a range of experience and perspectives. They included current and former public officials at the city (including Mayor White), former Texas Commission on Environmental Quality staff, faculty at local universities, industry representatives, and environmental public health advocates. Some of the city's tools were successful in meeting their designers' intent, some were less successful. Ultimately, even those tools that did not achieve their stated purpose were nonetheless successful in bringing attention and resources to the air quality issue. Through a series of pleas and prods, the city managed to draw attention to the problem locally and get reluctant policymakers at higher levels of government to respond. This work demonstrates the potential for local government to overcome limitations in the federal regulatory regime for air toxics control, shifting the balance of local, state, and federal initiative. It also highlights the importance of flexible, cooperative strategies in local environmental protection.^

GENETIC ANALYSIS OF THE HIPPO PATHWAY IN MOUSE LIVER

Cancer therapy and tumor treatment remain unsolved puzzles. Genetic screening for tumor suppressor genes in Drosophila revealed the Hippo-signaling pathway as a kinase cascade consisting of five core components. Disrupting the pathway by deleting the main component genes breaks the balance of cell proliferation and apoptosis and results in epithelial tissue tumorigenesis. The pathway is therefore believed to be a tumor suppressor pathway. However, a corresponding role in mammals is yet to be determined. Our lab began to investigate the tumor suppression function of the potent mammalian Hippo pathway by putting floxed alleles into the mouse genome flanking the functional-domain-expressing exons in each component (Mst1, Mst2, Sav1, Lats1 and Lats2). These mice were then crossed with different cre-mouse lines to generate conditional knockout mice. Results indicate a ubiquitous tumor suppression function of these components, predominantly in the liver. A further liver specific analysis of the deletion mutation of these components, as well as the Yap/Taz double deletion mutation, reveals essential roles of the Hippo pathway in regulating hepatic quiescence and embryonic liver development. One of the key cellular mechanisms for the Hippo pathway’s involvement in these liver biological events is likely its cell cycle regulation function. Our work will help to develop potential therapeutic approaches for liver cancer.

Policy analysis of shifting to the state-run Texas women's health program

During the 82nd Texas legislature, state leaders passed a provision stating that healthcare providers, who perform, promote, or affiliate with providers who perform or promote elective abortion services may not be eligible to participate in the Texas Medicaid Women's Health Program (WHP). The federal government reacted to this new provision by vowing to eliminate its 90% share of program support on the grounds that the provision violated a patient's freedom to choose a provider; a right protected by the Social Security Act. Texas leaders stated that the Women's Health Program would continue without federal support, financed exclusively with state funds.^ The following policy analysis compares the projected impact of the current Medicaid Women's Health Program to the proposed state-run program using the criteria-alternative matrix framework. The criteria used to evaluate the program alternatives include population affected, unintended pregnancy and abortion impact, impact on cervical cancer rate, and state-level government expenditures. Each criterion was defined by selected measures. The population affected was measured by the number of women served in the programs. Government expenditures were measured in terms of payments for program costs, Medicaid delivery costs, and cervical cancer diagnostic costs. Unintended pregnancy impact was measured by the number of projected unplanned pregnancies and abortions under each alternative. The impact on cervical cancer was projected in terms of the number of new cervical cancer cases under each alternative. Differences in the projections with respect to each criterion were compared to assess the impact of shifting to the state-only policy.^ After examining program alternatives, it is highly recommended that Texas retain the Medicaid WHP. If the state does decide to move forward with the state-run WHP, it is recommended that the program run at its previous capacity. Furthermore, for the purpose of addressing the relatively high cervical cancer incidence rate in Texas, incorporating HPV vaccination coverage for women ages 18-26 as part of the Women's Health Program is recommended.^

Accumulation rates of ODP Site 177-1090

Dust has the potential to modify global climate by influencing the radiative balance of the atmosphere and by supplying iron and other essential limiting micronutrients to the ocean (Martin et al., 1990, doi:10.1038/345156a0; Martin, 1990, doi:10.1029/PA005i001p00001). Indeed, dust supply to the Southern Ocean increases during ice ages, and 'iron fertilization' of the subantarctic zone may have contributed up to 40 parts per million by volume (p.p.m.v.) of the decrease (80-100 p.p.m.v.) in atmospheric carbon dioxide observed during late Pleistocene glacial cycles (Watson et al., 2000, doi:10.1038/35037561; Kohfeld et al., 2005, doi:10.1126/science.1105375; Martínez-Garcia et al., 2009, doi:10.1029/2008PA001657; Sigman et al., 2010, doi:10.1038/nature09149; Hain et al., 2010, doi:10.1029/2010gb003790). So far, however, the magnitude of Southern Ocean dust deposition in earlier times and its role in the development and evolution of Pleistocene glacial cycles have remained unclear. Here we report a high-resolution record of dust and iron supply to the Southern Ocean over the past four million years, derived from the analysis of marine sediments from ODP Site 1090, located in the Atlantic sector of the subantarctic zone. The close correspondence of our dust and iron deposition records with Antarctic ice core reconstructions of dust flux covering the past 800,000 years (Lambert et al., 2008, doi:10.1038/nature06763; Wolf et al., 2006, doi:10.1038/nature04614) indicates that both of these archives record large-scale deposition changes that should apply to most of the Southern Ocean, validating previous interpretations of the ice core data. The extension of the record beyond the interval covered by the Antarctic ice cores reveals that, in contrast to the relatively gradual intensification of glacial cycles over the past three million years, Southern Ocean dust and iron flux rose sharply at the Mid-Pleistocene climatic transition around 1.25 million years ago. This finding complements previous observations over late Pleistocene glacial cycles (Martínez-Garcia et al., 2009; Lambert et al., 2008; Wolff et al., 2006), providing new evidence of a tight connection between high dust input to the Southern Ocean and the emergence of the deep glaciations that characterize the past one million years of Earth history.

Table 1: Discharge, mass flux, maximum velocity and ice thickness of glaciers from Dronning Maud Land, Antarctica

Mass transport and mass flux values for the different types of glaciers in the Sør-Rondane are calculated from computer models, based upon gravity data and geodetic stake velocity measurements. The results are interpreted in the light of a general flow line analysis, glacial geological investigations and of the ablation terms of the mass balance for Dronning Maud Land and Antarctica.