Extraction of lateral eigenmode properties in thin film bulk acoustic wave resonator from interferometric measurements

A heterodyne laser interferometer is used to study acoustic wave fields excited in a 1.8 GHz AlN thin film bulk acoustic waveresonator. The electrical response of the resonator exhibits a strong thickness resonance onto which spurious modes, caused by lateral standing plate waves, are superposed. Optical interferometermeasurements are used to extract dispersion curves of the laterally propagating waves responsible for the spurious responses. A discrete eigenmode spectrum due to the finite lateral dimensions of the resonator is observed. An equivalent circuit model for a multimode resonator is fitted to the mechanical resonator response extracted along a single curve in the dispersion diagram, and is used to determine properties, such as Q-values, of the individual lateral eigenmodes.Measuredwave field images, extracted dispersion curves, and the eigenmode spectrum with the model fitting results are presented.Peer reviewe

Labeling the human skeleton with 41Ca to assess changes in bone calcium metabolism

Bone research is limited by the methods available for detecting changes in bone metabolism. While dual X-ray absorptiometry is rather insensitive, biochemical markers are subject to significant intra-individual variation. In the study presented here, we evaluated the isotopic labeling of bone using 41Ca, a long-lived radiotracer, as an alternative approach. After successful labeling of the skeleton, changes in the systematics of urinary 41Ca excretion are expected to directly reflect changes in bone Ca metabolism. A minute amount of 41Ca (100nCi) was administered orally to 22 postmenopausal women. Kinetics of tracer excretion were assessed by monitoring changes in urinary 41Ca/40Ca isotope ratios up to 700days post-dosing using accelerator mass spectrometry and resonance ionization mass spectrometry. Isotopic labeling of the skeleton was evaluated by two different approaches: (i) urinary 41Ca data were fitted to an established function consisting of an exponential term and a power law term for each individual; (ii) 41Ca data were analyzed by population pharmacokinetic (NONMEM) analysis to identify a compartmental model that describes urinary 41Ca tracer kinetics. A linear three-compartment model with a central compartment and two sequential peripheral compartments was found to best fit the 41Ca data. Fits based on the use of the combined exponential/power law function describing urinary tracer excretion showed substantially higher deviations between predicted and measured values than fits based on the compartmental modeling approach. By establishing the urinary 41Ca excretion pattern using data points up to day 500 and extrapolating these curves up to day 700, it was found that the calculated 41Ca/40Ca isotope ratios in urine were significantly lower than the observed 41Ca/40Ca isotope ratios for both techniques. Compartmental analysis can overcome this limitation. By identifying relative changes in transfer rates between compartments in response to an intervention, inaccuracies in the underlying model cancel out. Changes in tracer distribution between compartments were modeled based on identified kinetic parameters. While changes in bone formation and resorption can, in principle, be assessed by monitoring urinary 41Ca excretion over the first few weeks post-dosing, assessment of an intervention effect is more reliable ∼150days post-dosing when excreted tracer originates mainly from bon

Population pharmacokinetics of fluconazole given for secondary prevention of oropharyngeal candidiasis in HIV-positive patients.

To determine fluconazole population pharmacokinetics and explore the relationships between fluconazole average concentration and treatment effectiveness or microbiological resistance induction during a study aimed at evaluating the efficacy, tolerability and resistance induction after secondary prevention with fluconazole (150 mg weekly) versus placebo in human immunodeficiency virus-positive (HIV+) patients with oropharyngeal candidiasis. Population pharmacokinetic parameters of fluconazole determined from 458 serum drug concentration measurements obtained over 37 months in 132 HIV + patients not receiving highly active antiretroviral therapy. Mean estimates and variabilities were generated using non-linear regression analysis. Logistic and linear regression analyses were used to explore the relationships between the estimated average concentration of fluconazole and candidiasis relapse or fungal resistance towards fluconazole. Fluconazole kinetics were best described by a one-compartment model with first-order oral absorp tion from the gastrointestinal tract. The pharmacokinetics were influenced only by body weight. No effect was observed for gender, age, height or lymphocyte CD4 counts. The mean apparent population clearance was 0.79 l/h, the volume of distribution 571 and the absorption constant (ka) 0.93 h(-1). Inter-occasion variability in clearance (45%) was large relative to intersubject variability (21%). Taking into account the average fluconazole concentration or the time above the minimal inhibitory concentrations did not clinically improve the prediction of the occurrence of oropharyngeal relapse or microbiological resistance. The relationship between fluconazole concentrations and preventive effectiveness was poor. Together with the rather large inter-occasion variability in fluconazole clearance, this suggests no role of therapeutic drug monitoring in optimising fluconazole treatment for secondary prevention

Healthcare costs and utilization for Medicare beneficiaries with Alzheimer's

<p>Abstract</p> <p>Background</p> <p>Alzheimer's disease (AD) is a neurodegenerative disorder incurring significant social and economic costs. This study uses a US administrative claims database to evaluate the effect of AD on direct healthcare costs and utilization, and to identify the most common reasons for AD patients' emergency room (ER) visits and inpatient admissions.</p> <p>Methods</p> <p>Demographically matched cohorts age 65 and over with comprehensive medical and pharmacy claims from the 2003–2004 MEDSTAT MarketScan^®Medicare Supplemental and Coordination of Benefits (COB) Database were examined: 1) 25,109 individuals with an AD diagnosis or a filled prescription for an exclusively AD treatment; and 2) 75,327 matched controls. Illness burden for each person was measured using Diagnostic Cost Groups (DCGs), a comprehensive morbidity assessment system. Cost distributions and reasons for ER visits and inpatient admissions in 2004 were compared for both cohorts. Regression was used to quantify the marginal contribution of AD to health care costs and utilization, and the most common reasons for ER and inpatient admissions, using DCGs to control for overall illness burden.</p> <p>Results</p> <p>Compared with controls, the AD cohort had more co-morbid medical conditions, higher overall illness burden, and higher but less variable costs ($13,936 s.$10,369; Coefficient of variation = 181 vs. 324). Significant excess utilization was attributed to AD for inpatient services, pharmacy, ER visits, and home health care (all p < 0.05). In particular, AD patients were far more likely to be hospitalized for infections, pneumonia and falls (hip fracture, syncope, collapse).</p> <p>Conclusion</p> <p>Patients with AD have significantly more co-morbid medical conditions and higher healthcare costs and utilization than demographically-matched Medicare beneficiaries. Even after adjusting for differences in co-morbidity, AD patients incur excess ER visits and inpatient admissions.</p

Overshoot mechanism in transient excitation of THz and Gunn oscillations in wide-bandgap semiconductors

A detailed study of high-field transient and direct-current (DC) transport in GaN-based Gunn diode oscillators is carried out using the commercial simulator Sentaurus Device. Applicability of drift-diffusion (DD) and hydrodynamic (HD) models to high-speed, highfrequency devices is discussed in depth, and the results of the simulations from these models are compared. It is shown, for a highly homogeneous device based on a short (2 μm) supercritically doped (1017 cm-3) GaN specimen, that the DD model is unable to correctly take into account some essential physical effects which determine the operation mode of the device. At the same time, the HD model is ideally suited to solve such problems due to its ability to incorporate non-local effects. We show that the velocity overshoot near the device contacts and space charge injection and extraction play a crucial role in defining the operation mode of highly homogeneous short diodes in both the transient regime and the voltagecontrolled oscillation regime. The transient conduction current responses are fundamentally different in the DD and HD models. The DD current simply repeats the velocity-field (v-F) characteristics, and the sample remains in a completely homogeneous state. In the HD model, the transient current pulse with a full width at half maximum of approximately 0.2 ps is increased about twofold due to the carrier injection (extraction) into (from) the active region and the velocity overshoot. The electron gas is characterized by highly inhomogeneous distributions of the carrier density, the electric field and the electron temperature. The simulation of the DC steady states of the diodes also shows very different results for the two models. The HD model shows the trapped stable anodic domain in the device, while the DD model completely retains all features of the v-F characteristics in a homogeneous gas. Simulation of the voltage-controlled oscillator shows that it operates in the accumulation layer mode generating microwave signals at 0.3 to 0.7 THz. In spite of the fact that the known criterion of a Gunn domain mode n0L > (n0L)0 was satisfied, no Gunn domains were observed. The explanation of this phenomenon is given. © 2012 Momox et al

Development and validation of a risk model for predicting adverse drug reactions in older people during hospital stay: Brighton Adverse Drug Reactions Risk (BADRI) model

BACKGROUND: Older patients are at an increased risk of developing adverse drug reactions (ADR). Of particular concern are the oldest old, which constitute an increasingly growing population. Having a validated clinical tool to identify those older patients at risk of developing an ADR during hospital stay would enable healthcare staff to put measures in place to reduce the risk of such an event developing. The current study aimed to (1) develop and (2) validate an ADR risk prediction model. METHODS: We used a combination of univariate analysis and multivariate binary logistic regression to identify clinical risk factors for developing an ADR in a population of older people from a UK teaching hospital. The final ADR risk model was then validated in a European population (European dataset). RESULTS: Six-hundred-ninety patients (median age 85 years) were enrolled in the development stage of the study. Ninety-five reports of ADR were confirmed by independent review in these patients. Five clinical variables were identified through multivariate analysis and included in our final model; each variable was attributed a score of 1. Internal validation produced an AUROC of 0.74, a sensitivity of 80%, and specificity of 55%. During the external validation stage the AUROC was 0.73, with sensitivity and specificity values of 84% and 43% respectively. CONCLUSIONS: We have developed and successfully validated a simple model to use ADR risk score in a population of patients with a median age of 85, i.e. the oldest old. The model is based on 5 clinical variables (≥8 drugs, hyperlipidaemia, raised white cell count, use of anti-diabetic agents, length of stay ≥12 days), some of which have not been previously reported