Decomposition of disparities in life expectancy with applications to administrative health claims and registry data.

Research shows that geographic disparities in life expectancy between leading and lagging states are increasing over time while racial disparities between Black and White Americans have been going down. In the 65+ age strata morbidity is the most common cause of death, making differences in morbidity and associated adverse health-related outcomes between advantaged and disadvantaged groups an important aspect of disparities in life expectancy at age 65 (LE65). In this study, we used Pollard's decomposition to evaluate the disease-related contributions to disparities in LE65 for two types of data with distinctly differing structures: population/registry and administrative claims. To do so, we analyzed Pollard's integral, which is exact by construction, and developed exact analytic solutions for both types of data without the need for numerical integration. The solutions are broadly applicable and easily implemented. Applying these solutions, we found that the largest relative contributions to geographic disparities in LE65 were chronic lower respiratory diseases, circulatory diseases, and lung cancer; and, to racial disparities: arterial hypertension, diabetes mellitus, and cerebrovascular diseases. Overall, the increase in LE65 observed over 1998-2005 and 2010-2017 was primarily due to a reduction in the contributions of acute and chronic ischemic diseases; this was partially offset by increased contributions of diseases of the nervous system including dementia and Alzheimer's disease.

Forecasting prevalence and mortality of Alzheimer's disease using the partitioning models.

OBJECTIVES: Health forecasting is an important aspect of ensuring that the health system can effectively respond to the changing epidemiological environment. Common models for forecasting Alzheimer's disease and related dementias (AD/ADRD) are based on simplifying methodological assumptions, applied to limited population subgroups, or do not allow analysis of medical interventions. This study uses 5 %-Medicare data (1991-2017) to identify, partition, and forecast age-adjusted prevalence and incidence-based mortality of AD as well as their causal components. METHODS: The core underlying methodology is the partitioning analysis that calculates the relative impact each component has on the overall trend as well as intertemporal changes in the strength and direction of these impacts. B-spline functions estimated for all parameters of partitioning models represent the basis for projections of these parameters in future. RESULTS: Prevalence of AD is predicted to be stable between 2017 and 2028 primarily due to a decline in the prevalence of pre-AD-diagnosis stroke. Mortality, on the other hand, is predicted to increase. In all cases the resulting patterns come from a trade-off of two disadvantageous processes: increased incidence and disimproved survival. Analysis of health interventions demonstrates that the projected burden of AD differs significantly and leads to alternative policy implications. DISCUSSION: We developed a forecasting model of AD/ADRD risks that involves rigorous mathematical models and incorporation of the dynamics of important determinative risk factors for AD/ADRD risk. The applications of such models for analyses of interventions would allow for predicting future burden of AD/ADRD conditional on a specific treatment regime.

Underlying mechanisms of change in cancer prevalence in older U.S. adults: contributions of incidence, survival, and ascertainment at early stages.

PURPOSE: To quantitatively evaluate contributions of trends in incidence, relative survival, and stage at diagnosis to the dynamics in the prevalence of major cancers (lung, prostate, colon, breast, urinary bladder, ovaries, stomach, pancreas, esophagus, kidney, liver, and skin melanoma) among older U.S. adults age 65 +. METHODS: Trend partitioning was applied to the Surveillance, Epidemiology, and End Results Program data for 1973-2016. RESULTS: Growth of cancer prevalence in older adults decelerated or even decreased over time for all studied cancers due to decreasing incidence and improving survival for most of cancers, with a smaller contribution of the stage at cancer diagnosis. Changes in the prevalence of cancers of the lung, colon, stomach, and breast were predominantly due to decreasing incidence, increasing survival and more frequent diagnoses at earlier stages. Changes in prevalence of some other cancers demonstrated adverse trends such as decreasing survival in localized and regional stages (urinary bladder and ovarian) and growing impact of late-stage diagnoses (esophageal cancer). CONCLUSION: While decelerating or decreasing prevalence of many cancers were due to a beneficial combination of decreasing incidence and increasing survival, there are cancers for which decelerating prevalence is due to lack of improvement in their stage-specific survival and/or increasing frequency of diagnosis at advanced stages. Overall, if the observed trends persist, it is likely that the burden associated with cancer prevalence in older U.S. adults will be lower  comparing to projections based on constant increasing prevalence have previously estimated.

Doppler backscattering diagnostic with dual homodyne detection on the Globus-M compact spherical tokamak.

This article considers a four-frequency microwave Doppler backscattering (DBS) system in the compact spherical tokamak Globus-M. The hardware was adequate for the purposes of studying the peripheral plasma in the tokamak. The multichannel DBS system is based on duplication of a dual homodyne detection circuit for four incident Ka-band frequencies. The ray tracing results for a spherical torus are described, and specific requirements for the antenna tilt adjustment are defined. Some new experimental results are given for using DBS diagnostics on the Globus-M tokamak in order to illustrate its efficiency.

A forecasting model of disease prevalence based on the McKendrick-von Foerster equation.

A new model for disease prevalence based on the analytical solutions of McKendric-von Foerster's partial differential equations is developed. Derivation of the model and methods to cross check obtained results are explicitly demonstrated. Obtained equations describe the time evolution of the healthy and unhealthy age-structured sub-populations and age patterns of disease prevalence. The projection of disease prevalence into the future requires estimates of time trends of age-specific disease incidence, relative survival functions, and prevalence at the initial age and year available in the data. The computational scheme for parameter estimations using Medicare data, analytical properties of the model, application for diabetes prevalence, and relationship with partitioning models are described and discussed. The model allows natural generalization for the case of several diseases as well as for modeling time trends in cause-specific mortality rates.

Peculiar Effects of Electromagnetic Millimeter Waves on Tumor Development in BALB/c Mice.

The study examined the effects of millimeter electromagnetic waves at a frequency of 130 GHz corresponding to the molecular absorption and radiation spectra of NO and O2 with the total exposition time of 6 h on tumor morphogenesis in 3- and 6-month-old tumor-prone BALB/c mice of both sexes. In experimental mice exposed to electromagnetic radiation, the development of cancer process was slowed down throughout the observation period; moreover, no macroscopic signs of the tumors were revealed. However, in contrast to control mice, experimental animals demonstrated the formation of pathological reactions reflected by hepatic biochemical indices accompanied by the development of dystrophic and microcirculatory alterations in the liver tissue.

Effects of Electromagnetic Fields Modulated by Infralow Frequencies on the Production of Stem Cells.

Experimental validation of the method for regulation of stem cell proliferation and differentiation is carried out. The method consists in exposure to ultrahigh frequency electromagnetic radiation, modulated by infralow frequencies with variable parameters. A specially designed programmer, setting up the parameters of exposure, is connected to the source of radiation. The zones of anatomical location of the red bone marrow of rats were exposed for 15 min to the amplitude-modulated electromagnetic radiation of ultrahigh frequency range. The parameters of exposure were determined in previous studies. The red bone marrow was collected from the sternum and head of the femur. The cellular composition of the red bone marrow was evaluated 1, 2, 3, and 6 days after the exposure. The optimal therapeutic mode of irradiation was then chosen, leading to stem cell activation with subsequent proliferation and differentiation into mature red bone marrow cells.

Theory of partitioning of disease prevalence and mortality in observational data.

In this study, we present a new theory of partitioning of disease prevalence and incidence-based mortality and demonstrate how this theory practically works for analyses of Medicare data. In the theory, the prevalence of a disease and incidence-based mortality are modeled in terms of disease incidence and survival after diagnosis supplemented by information on disease prevalence at the initial age and year available in a dataset. Partitioning of the trends of prevalence and mortality is calculated with minimal assumptions. The resulting expressions for the components of the trends are given by continuous functions of data. The estimator is consistent and stable. The developed methodology is applied for data on type 2 diabetes using individual records from a nationally representative 5% sample of Medicare beneficiaries age 65+. Numerical estimates show excellent concordance between empirical estimates and theoretical predictions. Evaluated partitioning model showed that both prevalence and mortality increase with time. The primary driving factors of the observed prevalence increase are improved survival and increased prevalence at age 65. The increase in diabetes-related mortality is driven by increased prevalence and unobserved trends in time-periods and age-groups outside of the range of the data used in the study. Finally, the properties of the new estimator, possible statistical and systematical uncertainties, and future practical applications of this methodology in epidemiology, demography, public health and health forecasting are discussed.

Triple-negative breast cancer: new perspectives for novel therapies.

Triple-negative breast cancer (TNBC) represents 10-20 % of all mammary tumors. It is often found in younger women and has been associated with poor prognosis, due to aggressive tumor phenotype(s), early metastasis to visceral organ or brain after chemotherapy and present lack of clinically established targeted therapies. In recent years, a greater understanding of the biology of this disease has led to the development of numerous and varied therapeutic approaches, especially the trials on poly (ADP-ribose) polymerase inhibitors BSI-201 and olaparib, and antiangiogenic agents such as bevacizumab and sunitinib, which have raised hopes in the treatment for TNBC and BRCA1/2-positive disease. But should these trials fail, what are the new possible perspectives we have in our hand to fight this disease? In the current review, we will assess mainly the possible future targeted therapeutic strategies, which could be the answer to our question in TNBC. Recent studies have shown several markers, which have roles in TNBC that could be possible targets for therapy. Some of these markers are p53-induced miR-205, leptin receptor antagonist peptide, enhancer of zeste homolog 2 and Notch 1 pathway components, each of them could offer different mechanism for target therapy in TNBC. Last but not least, vaccinia virus GLV-1h153 has shown exciting result in treating and preventing metastatic triple-negative breast cancer.

The quadratic hazard model for analyzing longitudinal data on aging, health, and the life span.

A better understanding of processes and mechanisms linking human aging with changes in health status and survival requires methods capable of analyzing new data that take into account knowledge about these processes accumulated in the field. In this paper, we describe an approach to analyses of longitudinal data based on the use of stochastic process models of human aging, health, and longevity which allows for incorporating state of the art advances in aging research into the model structure. In particular, the model incorporates the notions of resistance to stresses, adaptive capacity, and "optimal" (normal) physiological states. To capture the effects of exposure to persistent external disturbances, the notions of allostatic adaptation and allostatic load are introduced. These notions facilitate the description and explanation of deviations of individuals' physiological indices from their normal states, which increase the chances of disease development and death. The model provides a convenient conceptual framework for comprehensive systemic analyses of aging-related changes in humans using longitudinal data and linking these changes with genotyping profiles, morbidity, and mortality risks. The model is used for developing new statistical methods for analyzing longitudinal data on aging, health, and longevity.

A bivariate survival model with compound Poisson frailty.

A correlated frailty model is suggested for analysis of bivariate time-to-event data. The model is an extension of the correlated power variance function (PVF) frailty model (correlated three-parameter frailty model) (J. Epidemiol. Biostat. 1999; 4:53-60). It is based on a bivariate extension of the compound Poisson frailty model in univariate survival analysis (Ann. Appl. Probab. 1992; 4:951-972). It allows for a non-susceptible fraction (of zero frailty) in the population, overcoming the common assumption in survival analysis that all individuals are susceptible to the event under study. The model contains the correlated gamma frailty model and the correlated inverse Gaussian frailty model as special cases. A maximum likelihood estimation procedure for the parameters is presented and its properties are studied in a small simulation study. This model is applied to breast cancer incidence data of Swedish twins. The proportion of women susceptible to breast cancer is estimated to be 15 per cent.

Hormesis against aging and diseases: using properties of biological adaptation for health and survival improvement.

The idea of using hormesis for postponing aging and improving human health has been recently discussed in scientific literature. This paper shows that redundancy in renewal capacity, some portion of which become activated and manifested in hormesis effects, may originate as a result of interaction between living organisms and their environment. It is shown that such redundancy may normally exist for organisms in the wild, and not only in domesticated and laboratory animals. Further development of the hormesis idea requires: (i) investigating regularities of response to multiple stimuli; (ii) studying slow-time responses (e.g., physiological adaptation) to repeated stimuli; (iii) studying connection between slow and fast (e.g., developing at the cellular and sub-cellular levels) stress responses; (iv) translating knowledge accumulated in studies of animal model systems to humans; (v) evaluating unrealized potential for improving health and longevity using hormetic mechanisms. The use of mathematical and computer modeling for translating experimental knowledge about hormesis effects to humans, as well as connection between studying hormetic mechanisms and analyses of the age trajectories of physiological and biological indices affecting U-shapes curves of morbidity-mortality risks using longitudinal data on aging, health, and longevity are discussed.

Cumulative index of health disorders as an indicator of aging-associated processes in the elderly: results from analyses of the National Long Term Care Survey.

BACKGROUND: We employ an approach based on the elaborated frailty index (FI), which is capable of taking into account variables with mild effect on the aging, health and survival outcomes, and investigate the connections between the FI, chronological age and the aging-associated outcomes in the elderly. METHODS: Cross-sectional analysis of pooled data from the National Long Term Care Survey (NLTCS) assessing health and functioning of the U.S. elderly in 1982, 1984, 1989, 1994, and 1999. RESULTS: Distributions of frequency, residual life span, mortality rate, and relative risk of death are remarkably similar over age and FI. Coefficients of correlation between FI and age are low both for males (0.127, p<.01) and females (0.221, p<.01). The FI-specific age patterns show deceleration at advanced ages. The FI can provide order of magnitude better resolution in estimating mean remaining life span compared to age. Males have smaller FI than females while males' mortality risks are higher. For short-time horizons, the FI and age are largely independently associated with mortality risks. CONCLUSIONS: The FI: (i) can be considered as an adequate sex-specific indicator of the aging-associated processes in the elderly, (ii) can characterize these processes independently of age, and (iii) is a better characteristic of the aging phenotype than chronological age.

Experimental study of reproduction in C57Bl/6 and random-bred mice exposed to nonionizing high-frequency radiation.

Experimental study of changes in the reproductive function in 10 generations descending from C57Bl/6 and random-bred mice exposed to nonionizing radiation showed a trend to deviation of this function from the normal: the number of newborns in the litter of generations 3-5 was below the normal, which starting from generations 5-6 it gradually increased, approaching the normal.

Effect of low-intensity extremely high frequency radiation on reproductive function in wistar rats.

The exposure to low-intensity extremely high frequency electromagnetic radiation during spermatogenesis was accompanied by pathological changes, which resulted in degeneration and polymorphism of spermatozoa. The number of newborn rats increased in the progeny of irradiated animals.

Population models for the health effects of ionizing radiation.

In this paper we review recently-developed extension frailty, quadratic hazard, stochastic process, microsimulation, and linear latent structure models, which have the potential to describe the health effects of human populations exposed to ionizing radiation. We discuss the most common situations for which such models are appropriate. We also provide examples of how to estimate the parameters of these models from datasets of various designs. Carcinogenesis models are reviewed in context of application to epidemiologic data of population exposed to ionizing radiation. We also discuss the ways of how to generalize stochastic process and correlated frailty models for longitudinal and family analyses in radiation epidemiology.

Exposure to low-intensive superhigh frequency electromagnetic field as a factor of carcinogenesis in experimental animals.

Inbred albino mice and C57Bl/6 mice were exposed to nonthermal radiation of 37 GHz frequency in order to detect delayed effects caused by repeated irradiation. The detected pathomorphological changes and the dynamics of their formation suggest that these factors are responsible for delayed formation of immunodeficiency provoking mutagenic and carcinogenic effects.

Regulation of proteolytic activity of pepsin in rats [correction of mice] by rotating electromagnetic field.

In experiments on Wistar rats we studied the effect of low-frequency electromagnetic field rotating in either right-handed or a left-handed sense on proteolytic activity of pepsin. The right-handed rotating field increased, while left-handed rotating field decreased pepsin activity. Possible mechanisms of these changes in pepsin activity are discussed.

[A model of resource reallocation during physiological adaptation in Mediterranean fruit fly females]. / Model' pereraspredeleniia resursa v khode fiziologicheskoi adaptatsii samok sredizemnomorskoi fruktovoi mukhi Ceratitis capitata.

Analysis of experimental data on longevity and fertility of females of Mediterranean fruit fly Ceratitis capitata demonstrates that flies lay fewer eggs on the average as the average life-span increases. At the same time, the values of individual life-span and the number of eggs laid are positively correlated. To explain these results, a resource model describing the allocation and reallocation of resources between two basic functions, reproduction and maintenance, was proposed. The reallocation of resources, is triggered by changes in environmental conditions such as diet changes, and the parameters of reallocation depend on the current environmental conditions. Modeling demonstrated that the results of experiments are greatly influenced by population selection and heterogeneity.

Effect of rotating electromagnetic fields on proteolytic activity of pepsin in rats.

We studied the effect of 37-GHz electromagnetic field on proteolytic activity of pepsin in Wistar rats. The plane of polarization of the electromagnetic fields rotated in either right-handed or left-handed sense (D- and L-chirality). D-Polarization stimulated, while L-polarization suppressed pepsin production.