Effect of Passive Heating on Males and Females with Elevated Arterial Stiffness

Context: Cardiovascular disease (CVD) is one of the leading causes of mortality in the United States, accounting for about 1 in every 4 deaths annually. Studies have shown that passive heating does have some degree of effect on arterial stiffness, but not much is known about populations with higher stiffness. Objective: To examine the independent effect of core temperature increase during passive heating on arterial stiffness. Methods: Participants visited the lab three times; one familiarization and two experimental trials. The experimental trials consisted of subjects being passively heated in an environment of 40°C / 40% relative humidity (HEAT) or normal laboratory conditions (CONTROL). Participants were 48.9 ± 12.0 years old of age, 66.7± 12.6 kg, 168.2 ±8.8 cm, and 7.7 ± 2.0 m/s central pulse wave velocity. Main Outcome Measures: Before and after passive heating, pulse wave velocity (PWV measures occurred via ultrasound at the tibial, radial, femoral and carotid artery sites). At the same time, rectal temperature (Trec) was measured. Trec was measured with rectal thermistors; differences between trials confirm the changes that occurred as a result of environmental conditions. Central arterial stiffness was assessed by using measures between the carotid and femoral artery sites, while peripheral stiffness was assessed using the radial and tibial artery sites. The radial site was used for upper peripheral arterial stiffness and the tibial site was used for lower peripheral arterial stiffness. Results: Trec at the end of passive heating showed significant differences between the CONTROL and PASSIVE HEAT trials respectively (36.53 ± .16 vs. 38.14 ± .49°C; p \u3c 0.001). There were no interactions (p\u3e0.05) between time and condition for central pulse wave velocity (∆ 1.83 ± 50.44 vs. 3.25 ± 67.34 cm/s; for control and passive heating respectively), upper peripheral (∆ 51.50 ± 60.87 vs. 92.77 ± 82.81 cm/s), and lower peripheral pulse wave velocities (∆ 46.99 ± 68.55 vs. 23.70 ± 156.67 cm/s). Conclusions: The findings of this study indicate that differences in mean body temperature do not result in significant decreases in arterial stiffness following passive heating in individuals with poor arterial stiffness at baseline

Studying Effects of Primary Care Physicians and Patients on the Trade-Off Between Charges for Primary Care and Specialty Care Using a Hierarchical Multivariate Two-Part Model

Objective. To examine effects of primary care physicians (PCPs) and patients on the association between charges for primary care and specialty care in a point-of-service (POS) health plan. Data Source. Claims from 1996 for 3,308 adult male POS plan members, each of whom was assigned to one of the 50 family practitioner-PCPs with the largest POS plan member-loads. Study Design. A hierarchical multivariate two-part model was fitted using a Gibbs sampler to estimate PCPs\u27 effects on patients\u27 annual charges for two types of services, primary care and specialty care, the associations among PCPs\u27 effects, and within-patient associations between charges for the two services. Adjusted Clinical Groups (ACGs) were used to adjust for case-mix. Principal Findings. PCPs with higher case-mix adjusted rates of specialist use were less likely to see their patients at least once during the year (estimated correlation: –.40; 95% CI: –.71, –.008) and provided fewer services to patients that they saw (estimated correlation: –.53; 95% CI: –.77, –.21). Ten of 11 PCPs whose case-mix adjusted effects on primary care charges were significantly less than or greater than zero (p \u3c .05) had estimated, case-mix adjusted effects on specialty care charges that were of opposite sign (but not significantly different than zero). After adjustment for ACG and PCP effects, the within-patient, estimated odds ratio for any use of primary care given any use of specialty care was .57 (95% CI: .45, .73). Conclusions. PCPs and patients contributed independently to a trade-off between utilization of primary care and specialty care. The trade-off appeared to partially offset significant differences in the amount of care provided by PCPs. These findings were possible because we employed a hierarchical multivariate model rather than separate univariate models

A Hierarchical Multivariate Two-Part Model for Profiling Providers\u27 Effects on Healthcare Charges

Procedures for analyzing and comparing healthcare providers\u27 effects on health services delivery and outcomes have been referred to as provider profiling. In a typical profiling procedure, patient-level responses are measured for clusters of patients treated by providers that in turn, can be regarded as statistically exchangeable. Thus, a hierarchical model naturally represents the structure of the data. When provider effects on multiple responses are profiled, a multivariate model rather than a series of univariate models, can capture associations among responses at both the provider and patient levels. When responses are in the form of charges for healthcare services and sampled patients include non-users of services, charge variables are a mix of zeros and highly-skewed positive values that present a modeling challenge. For analysis of regressor effects on charges for a single service, a frequently used approach is a two-part model (Duan, Manning, Morris, and Newhouse 1983) that combines logistic or probit regression on any use of the service and linear regression on the log of positive charges given use of the service. Here, we extend the two-part model to the case of charges for multiple services, using a log-linear model and a general multivariate log-normal model, and employ the resultant multivariate two-part model as the within-provider component of a hierarchical model. The log-linear likelihood is reparameterized as proposed by Fitzmaurice and Laird (1993), so that regressor effects on any use of each service are marginal with respect to any use of other services. The general multivariate log-normal likelihood is constructed in such a way that variances of log of positive charges for each service are provider-specific but correlations between log of positive charges for different services are uniform across providers. A data augmentation step is included in the Gibbs sampler used to fit the hierarchical model, in order to accommodate the fact that values of log of positive charges are undefined for unused service. We apply this hierarchical, multivariate, two-part model to analyze the effects of primary care physicians on their patients\u27 annual charges for two services, primary care and specialty care. Along the way, we also demonstrate an approach for incorporating prior information about the effects of patient morbidity on response variables, to improve the accuracy of provider profiles that are based on patient samples of limited size

Code Cache Management in Managed Language VMs to Reduce Memory Consumption for Embedded Systems

The compiled native code generated by a just-in-time (JIT) compiler in man- aged language virtual machines (VM) is placed in a region of memory called the code cache. Code cache management (CCM) in a VM is responsible to find and evict methods from the code cache to maintain execution correctness and manage program performance for a given code cache size or memory budget. Effective CCM can also boost program speed by enabling more aggressive JIT compilation, powerful optimizations, and improved hardware instruction cache and I-TLB per- formance. Though important, CCM is an overlooked component in VMs. We find that the default CCM policies in Oracle’s production-grade HotSpot VM perform poorly even at modest memory pressure. We develop a detailed simulation-based frame- work to model and evaluate the potential efficiency of many different CCM poli- cies in a controlled and realistic, but VM-independent environment. We make the encouraging discovery that effective CCM policies can sustain high program performance even for very small cache sizes. Our simulation study provides the rationale and motivation to improve CCM strategies in existing VMs. We implement and study the properties of several CCM policies in HotSpot. We find that in spite of working within the bounds of the HotSpot VM’s current CCM sub-system, our best CCM policy implementation in HotSpot improves program performance over the default CCM algorithm by 39%, 41%, 55%, and 50% with code cache sizes that are 90%, 75%, 50%, and 25% of the desired cache size, on average

Clement Franklin Robinson Correspondence

Entries include brief biographical information, a typed biography, and a typed letter on Robinson & Richardson business stationery

Biodegradable PLGA Based Nanoparticles for Sustained Regional Lymphatic Drug Delivery

The purpose of this work is to evaluate biodegradable drug carriers with defined size, hydrophobicity, and surface charge density for preferential lymphatic uptake and retention for sustained regional drug delivery. PLGA–PMA:PLA-PEG (PP) nanoparticles of defined size and relative hydrophobicity were prepared by nanoprecipitation method. These were compared with PS particles of similar sizes and higher hydrophobicity. PLGA–PMA:PLGA-COOH (PC) particles at 80:20, 50:50, and 20:80 ratios were prepared by nanoprecipitation for the charge study. Particle size and zeta potential were characterized by dynamic light scattering and laser doppler anemometry, respectively. Particles were administered in vivo to rats subcutaneously. Systemic and lymph node uptake was evaluated by marker recovery. Lymphatic uptake and node retention of PP nanoparticles was shown to be inversely related to size. Lymphatic uptake and node retention of PP particles, as compared to PS particles, was shown to be inversely related to hydrophobicity. Lastly, lymphatic uptake and node retention of PC nanoparticles were directly related to the anionic charge on the particles. In vivo lymphatic uptake and retention in a rat model indicates that the 50 nm PP particles are ideal for sustained regional delivery into the lymphatics for prevention/treatment of oligometastases

Differential expression of microRNA-206 and its target genes in pre-eclampsia

Objectives: Pre-eclampsia is a multi-system disease that significantly contributes to maternal and fetal morbidity and mortality. In this study, we used a non-biased microarray approach to identify novel circulating miRNAs in maternal plasma that may be associated with pre-eclampsia. Methods: Plasma samples were obtained at 16 and 28 weeks of gestation from 18 women who later developed pre-eclampsia (cases) and 18 matched women with normotensive pregnancies (controls). We studied miRNA expression profiles in plasma and subsequently confirmed miRNA and target gene expression in placenta samples. Placental samples were obtained from an independent cohort of 19 women with pre-eclampsia matched with 19 women with normotensive pregnancies. Results: From the microarray, we identified 1 miRNA that was significantly differentially expressed between cases and controls at 16 weeks of gestation and 6 miRNAs that were significantly differentially expressed at 28 weeks. Following qPCR validation only one, miR-206, was found to be significantly increased in 28 week samples in women who later developed pre-eclampsia (1.4 fold change ± 0.2). The trend for increase in miR-206 expression was mirrored within placental tissue from women with pre-eclampsia. In parallel, IGF-1, a target gene of miR-206, was also found to be down-regulated (0.41 ± 0.04) in placental tissue from women with pre-eclampsia. miR-206 expression was also detectable in myometrium tissue and trophoblast cell lines. Conclusions: Our pilot study has identified miRNA-206 as a novel factor up-regulated in pre-eclampsia within the maternal circulation and in placental tissue