Global sensitivity analysis of a single-cell HBV model for viral dynamics in the liver.

The predictive accuracy of mathematical models representing anything ranging from the meteorological to the biological system profoundly depends on the quality of model parameters derived from experimental data. Hence, robust sensitivity analysis (SA) of these critical model parameters aids in sifting the influential from the negligible out of typically vast parameter regimes, thus illuminating key components of the system under study. We here move beyond traditional local sensitivity analysis to the adoption of global SA techniques. Partial rank correlation coefficient (PRCC) based on Latin hypercube sampling is compared with the variance-based Sobol method. We selected for this SA investigation an infection model for the hepatitis-B virus (HBV) that describes infection dynamics and clearance of HBV in the liver [Murray & Goyal, 2015]. The model tracks viral particles such as the tenacious and nearly ineradicable covalently closed circular DNA (cccDNA) embedded in infected nuclei and an HBV protein known as p36. Our application of these SA methods to the HBV model illuminates, especially over time, the quantitative relationships between cccDNA synthesis rate and p36 synthesis and export. Our results reinforce previous observations that the viral protein, p36, is by far the most influential factor for cccDNA replication. Moreover, both methods are capable of finding crucial parameters of the model. Though the Sobol method is independent of model structure (e.g., linearity and monotonicity) and well suited for SA, our results ensure that LHS-PRCC suffices for SA of a non-linear model if it is monotonic.

Characterization of the leukemogenic potential of distal cytoplasmic CSF3R truncation and missense mutations.

An increasing number of variants of unknown significance are being identified in leukemia patients with the application of deep sequencing and these include CSF3R cytoplasmic mutations. Previous studies have demonstrated oncogenic potential of certain CSF3R truncation mutations prior to internalization motifs. However, the oncogenic potential of truncating the more distal region of CSF3R cytoplasmic domain as well as cytoplasmic missense mutations remains uncharacterized. Here we identified that CSF3R distal cytoplasmic truncation mutations (Q793-Q823) also harbored leukemogenic potential. Mechanistically, these distal cytoplasmic truncation mutations demonstrated markedly decreased receptor degradation, probably owing to loss of the de-phosphorylation domain (residues N818-F836). Furthermore, all truncations prior to Q823 demonstrated increased expression of the higher molecular weight CSF3R band, which is shown to be essential for the receptor surface expression and the oncogenic potential. We further demonstrated that sufficient STAT5 activation is essential for oncogenic potential. In addition, CSF3R K704A demonstrated transforming capacity due to interruption of receptor ubiquitination and degradation. In summary, we have expanded the region of the CSF3R cytoplasmic domain in which truncation or missense mutations exhibit leukemogenic capacity, which will be useful for evaluating the relevance of CSF3R mutations in patients and helpful in defining targeted therapy strategies.

Accessibility of Antiretroviral Therapy in Ghana: Convenience of Access

The convenience of accessing antiretroviral therapy (ART) is important for initial access to care and subsequent adherence to ART. We conducted a qualitative study of people living with HIV/AIDS (PLWHA) and ART healthcare providers in Ghana in 2005. The objective of this study was to explore the participants' perceived convenience of accessing ART by PLWHA in Ghana. The convenience of accessing ART was evaluated from the reported travel and waiting times to receive care; the availability; or otherwise; of special considerations; with respect to the waiting time to receive care; for those PLWHA who were in active employment in the formal sector; the frequency of clinic visits before and after initiating ART; and whether the PLWHA saw the same or different providers at each clinic visit (continuity of care). This qualitative study used in-depth interviews based on Yin's case-study research design to collect data from 20 PLWHA and 24 ART healthcare providers as study participants. . Reported travel time to receive ART services ranged from 2 to 12 h for 30 of the PLWHA.. Waiting time to receive care was from 4 to 9 h. . While known government workers; such as teachers; were attended to earlier in some of the centres; this was not a consistent practice in all the four ART centres studied. . The PLWHA corroborated the providers' description of the procedure for initiating and monitoring ART in Ghana. . PLWHA did not see the same provider every time; but they were assured that this did not compromise the continuity of their care. Our study suggests that convenience of accessing ART is important to both PLWHA and ART healthcare providers; but the participants alluded to other factors; including open provider-patient communication; which might explain the PLWHA's understanding of the constraints under which they were receiving care. The current nation-wide coverage of the ART programme in Ghana; however; calls for the replication of this study to identify possible perception changes over time that may need attention. Our study findings can inform interventions to promote access to ART; especially in Africa

Enhanced central response to dehydration in mice lacking angiotensin AT(1a) receptors.

The objective was to determine the central nervous system (CNS) responses to dehydration (c-Fos and vasopressin mRNA) in mice lacking the ANG AT(1a) receptor [ANG AT(1a) knockout (KO)]. Control and AT(1a) KO mice were dehydrated for 24 or 48 h. Baseline plasma vasopressin (VP) was not different between the groups; however, the response to dehydration was attenuated in AT(1a) KO (24 +/- 11 vs. 10.6 +/- 2.7 pg/ml). Dehydration produced similar increases in plasma osmolality and depletion of posterior pituitary VP content. Neuronal activation was observed as increases in c-Fos protein and VP mRNA. The supraoptic responses were not different between groups. In the paraventricular nucleus (PVN), c-Fos-positive neurons (57.4 +/- 10.7 vs. 98.4 +/- 7.4 c-Fos cells/PVN, control vs. AT(1a) KO) and VP mRNA levels (1.0 +/- 0.1 vs. 1.4 +/- 0.1 microCi, control vs. AT(1a) KO) were increased with greater responses in AT(1a) KO. A comparison of 1- to 2-day water deprivation showed that plasma VP, brain c-Fos, and VP mRNA returned toward control on day 2, although plasma osmolality remained high. Data demonstrate that AT(1a) KO mice show a dichotomous response to dehydration, reduced for plasma VP and enhanced for PVN c-Fos protein and VP mRNA. The results illustrate the importance of ANG AT(1a) receptors in the regulation of osmotic and endocrine balance.

Medical care utilization by AFDC recipients under reformed Medicaid.

As Medicaid moves toward a system of managed care, Aid for Families with Dependent Children (AFDC) recipients often are assigned to an organization that assumes responsibility for managing their annual receipt of health care. This study reports the results of an investigation into the patterns of medical care utilization by AFDC recipients and their children under reformed Medicaid. The issues explored include whether or not medical care utilization patterns vary by race, and if there are identifiable factors that determine the utilization patterns of AFDC recipients and their children. We conclude that racial differences in medical care utilization do exist for AFDC recipients, but not for their children. Policy makers involved in reforming Medicaid should recognize that certain cohorts continue to exhibit undesirable medical care utilization patterns, and implement measures to rectify this situation.

Racial patterns in disabled elderly persons' use of medical services.

OBJECTIVE: This study examines the extent that older persons experience patterns of health service use that vary by race. METHODS: Using the 1989 NLTCS database, researchers estimate ten binomial logistic regressions of community medical service use by disabled White and Black older persons. Chow tests and Oaxaca decomposition analysis inform why racial differences continue to exist, although most elderly persons have Medicare. RESULTS: With similar medical conditions, Blacks are less likely to use services, particularly prescription medications and physician services. Use of some medical services is more likely for elderly Black persons who live in rural areas, small cities, and Western states, or who have more IADLs, joint and breathing problems, and broken parts. An Oaxaca decomposition indicates that differences in personal characteristics (e.g., income and health) do not fully explain racial differences in use of prescriptions and physician services. DISCUSSION: For reasons that are unrelated to financial assets, blacks remain vulnerable in their ability to access services commonly used by older persons. To remedy racial disparities in medical utilization, public policy must expand its focuses beyond health finance issues and consider differences in availability, accessibility, and acceptability.

Opportunity wages and workforce adjustments: understanding the cost of in-home elder care.

Time spent providing informal care represents a real cost to caregivers and potentially affects their decisions about alternative activities, including paid work. This study offers estimates of opportunity wages incurred by informal caregivers and explores the impact of these costs on their decisions to reduce or abandon workforce participation. We consider caregivers at two points in time: 1982 and 1989. Our estimates of caregivers' imputed wages vary more widely and range higher than those reported elsewhere, varying from $0.78 to $27.18 per hour, compared to values in the literature ranging from $4.64 to $10.30. In both years, caregivers with higher imputed wages were significantly more likely to work, with this effect stronger in 1989 as all noneconomic factors became less important. However, accommodation (working fewer hours or foregoing job opportunities) decreased with higher imputed wages in 1982 only. In 1989, elders' frailty became a significant determinant of accommodation.

Conceptualizing race in economic models of medical utilization: a case study of community-based elders and the emergency room.

There is no consensus on the appropriate conceptualization of race in economic models of health care. This is because race is rarely the primary focus for analysis of the market. This article presents an alternative framework for conceptualizing race in health economic models. A case study is analyzed to illustrate the value of the alternative conceptualization. The case study findings clearly document the importance of model stratification according to race. Moreover, the findings indicate that empirical results are improved when medical utilization models are refined in a way that reflects the unique experiences of the population that is studied.

Health characteristics and utilization of public sector health facilities among migrant agricultural workers in Orange County, New York.

Publicly subsidized medical clinics were established to provide migrant farmworkers with minimal access to mainstream medical care. Nevertheless, migrant farmworkers delay treatment of health problems and refrain totally from use of medical facilities. The present study explores the health status and utilization of subsidized migrant clinics by farmworkers in a vegetable production county (Orange County) in upstate New York. Multivariate analysis indicated that economic resources, mental health status, health insurance coverage, language, education and utilization of acute care facilities are important predictors of these decisions.

The economic returns from investments in physical and mental health: a case study of migrant farmworkers in rural New York.

Spiraling costs of medical care services and limited federal and state resources necessitate discriminating and cost-effective strategies for financing health care to indigent populations. Thus, while the selection among intervention strategies is aided by information on both the cost and benefits of program alternatives, data on the latter aspect is more difficult to obtain. Human capital research provides a mechanism for assessing one of the multifarious aspects of the benefits of medical services. Research suggests that labor market earnings opportunities are affected by health status. The present study explores this relationship for migrant farmworkers in a vegetable production county (Orange County) in upstate New York. Multivariate analysis indicated that mental well-being was an important predictor of earnings for migrant farmworkers. Directions for public health policy intervention strategies are also discussed.

Labor market choices and home health care provision among employed ethnic caregivers.

This paper systematically links and examines two decisions of employed informal caregivers, the allocation of time to care production and to the labor market. Its main contribution is its evaluation of the influence of ethnicity on the family's decisions about providing health care to meet the impending needs of an elderly family member or friend. Caregiving production factors, financial resources, and personal characteristics of the informal care providers influence both caregiving hours and the labor market decisions. German-, Irish-, English-, and Afro-Americans differ significantly in their decision to provide informal care. Policy and research implications of this analysis are discussed.

Ethnic differences in the production of informal home health care.

Informal health care providers (usually family members, friends, and other unpaid helpers) determine the quantity and quality of home health services received by the elderly. Yet our knowledge of informal health care production is limited, in sharp contrast to our detailed knowledge of market-produced home health services. This paper assesses family choices in the production of informal home care, with special attention given to the influence of ethnicity on family caregiving style.

Nonemergency visits to hospital emergency rooms: a comparison of blacks and whites.

Both blacks and whites go to hospital emergency rooms for nonemergency health problems. Age, marital status, and health conditions are significant sociodemographic determinants for blacks' visits on these occasions, while those for whites include sex, age, education, insurance, employment status, region of residence, and health conditions. Despite the significant differences in determinants, similar influences bear on the two groups' decision to utilize medical services generally. Discrete analyses are still needed of cultural and interracial variation affecting the use of health facilities, together with intensive assessment of community characteristics in which the facilities are located, especially among black populations.

Sociodemographic and health factors influencing black and Hispanic use of the hospital emergency room.

The factors influencing the increased use of emergency rooms by minorities were examined among a national sample of black and Hispanic Americans. Multivariate analysis indicated that ethnicity and age were important predictors of emergency room use. Specific health conditions also determined whether the emergency room was chosen as a health care option. Directions for future research on emergency room use are presented.