Cohort Profile: The Precipitating Events Project (PEP Study).

The Precipitating Events Project (PEP Study) is an ongoing longitudinal study of 754 nondisabled community-living persons age 70 years or older who were members of a large health plan in greater New Haven, Connecticut, USA. The study was established to rigorously evaluate the epidemiology of disability in older persons and to elucidate the role of intervening illnesses and injuries on the disabling process. Of the eligible members, 75.2% agreed to participate and were enrolled between March 1998 and October 1999. Participants have completed comprehensive home-based assessments at 18-month intervals and have been interviewed monthly over the phone with a completion rate of 99%. Detailed participant-level data on health care utilization are obtained annually through linkages with Medicare claims. Through June 2019, 702 (93.1%) participants have died after a median of 109 months, while 43 (5.7%) have dropped out of the study after a median of 27 months. Death certificates are available for all decedents. To date, 117 original reports have been published using data from the PEP Study, including many focusing on other high priority areas such as end of life, frailty, depressive symptoms, aging stereotypes, pain, sleep, and methodologic research. The PEP Study welcomes proposals to access data for meritorious analyses from qualified investigators.

An Empirical Method of Detecting Time-Dependent Confounding: An Observational Study of Next Day Delirium in a Medical ICU.

Longitudinal research on older persons in the medical intensive care unit (MICU) is often complicated by the time-dependent confounding of concurrently administered interventions such as medications and intubation. Such temporal confounding can bias the respective longitudinal associations between concurrently administered treatments and a longitudinal outcome such as delirium. Although marginal structural models address time-dependent confounding, their application is non-trivial and preferably justified by empirical evidence. Using data from a longitudinal study of older persons in the MICU, we constructed a plausibility score from 0 - 10 where higher values indicate higher plausibility of time-dependent confounding of the association between a time-varying explanatory variable and an outcome. Based on longitudinal plots, measures of correlation, and longitudinal regression, the plausibility scores were compared to the differences in estimates obtained with non-weighted and marginal structural models of next day delirium. The plausibility scores of the three possible pairings of daily doses of fentanyl, haloperidol, and intubation indicated the following: low plausibility for haloperidol and intubation, moderate plausibility for fentanyl and haloperidol, and high plausibility for fentanyl and intubation. Comparing multivariable models of next day delirium with and without adjustment for time-dependent confounding, only intubation's association changed substantively. In our observational study of older persons in the MICU, the plausibility scores were generally reflective of the observed differences between coefficients estimated from non-weighted and marginal structural models.

Free space millimeter wave-coupled electro-optic high speed nonlinear polymer phase modulator with in-plane slotted patch antennas.

We report in-plane slotted patch antenna-coupled electro-optic phase modulators with a carrier-to-sideband ratio (CSR) of 22 dB under an RF power density of 120 W/m(2) and a figure of merit of 2.0 W(-1/2) at the millimeter wave frequencies of 36-37 GHz based on guest-host type of second-order nonlinear polymer SEO125. CSR was improved more than 20 dB by using a SiO(2) protection layer. We demonstrate detection of 3 GHz modulation of the RF carrier. We also derive closed-form expressions for the modulated phase of optical wave and carrier-to-sideband ratio. Design, simulation, fabrication, and experimental results are discussed.

Photothermal response in dual-gated bilayer graphene.

The photovoltaic and bolometric photoresponse in gapped bilayer graphene was investigated by optical and transport measurements. A pulse coincidence technique at 1.5 µm was used to measure the response times as a function of temperature. The bolometric and photovoltaic response times were found to be identical implying that the photovoltaic response is also governed by hot electron thermal relaxation. Response times of τ ∼ 100-20 ps were found for temperatures from 3-100 K. Above 10 K, the relaxation time was observed to be τ = 25 ± 5 ps, independent of temperature within noise.

Deaths observed in Medicare beneficiaries: average attributable fraction and its longitudinal extension for many diseases.

Calculating the longitudinal extension of the average attributable fraction (LE-AAF) for many risk factors (RFs) requires a two-stage computational process using only those combinations of RFs observed in the dataset. We first screen candidates RFs in a Cox Model, and assuming piecewise constant hazards, use pooled logistic regression to model the probability of death as a function of combinations of selected RFs. We average the iterative differencing of the attributable fractions calculated for all overlapping subsets of co-occurring RFs to obtain a LE-AAF for each RF that is additive and symmetrical. We illustrate by partitioning the additive proportions of death from 10 different groupings of acute and chronic diseases, on a national sample of older persons from the US (Medicare Beneficiary Survey) over a 4-year period and compare with results reported by the National Center for Healthcare Statistics. We conclude that careful screening of RFs with analysis restricted to extant combinations greatly reduces computational burden. LE-AAF accounted for a cumulative total of 66% of the deaths in our sample, compared with the 83% accounted for by the National Center for Healthcare Statistics.

Bayesian hierarchical modeling for a non-randomized, longitudinal fall prevention trial with spatially correlated observations.

Because randomization of participants is often not feasible in community-based health interventions, non-randomized designs are commonly employed. Non-randomized designs may have experimental units that are spatial in nature, such as zip codes that are characterized by aggregate statistics from sources like the U.S. census and the Centers for Medicare and Medicaid Services. A perennial concern with non-randomized designs is that even after careful balancing of influential covariates, bias may arise from unmeasured factors. In addition to facilitating the analysis of interventional designs based on spatial units, Bayesian hierarchical modeling can quantify unmeasured variability with spatially correlated residual terms. Graphical analysis of these spatial residuals demonstrates whether variability from unmeasured covariates is likely to bias the estimates of interventional effect. The Connecticut Collaboration for Fall Prevention is the first large-scale longitudinal trial of a community-wide healthcare intervention designed to prevent injurious falls in older adults. Over a two-year evaluation phase, this trial demonstrated a rate of fall-related utilization at hospitals and emergency departments by persons 70 years and older in the intervention area that was 11 per cent less than that of the usual care area, and a 9 per cent lower rate of utilization from serious injuries. We describe the Bayesian hierarchical analysis of this non-randomized intervention with emphasis on its spatial and longitudinal characteristics. We also compare several models, using posterior predictive simulations and maps of spatial residuals.

Linearized electrooptic microwave downconversion using phase modulation and optical filtering.

We propose and demonstrate an electrooptic technique for relaying microwave signals over an optical fiber and downconverting the microwave signal to an intermediate frequency at the receiver. The system uses electrooptic phase modulation in the transmitter to impose the microwave signal on an optical carrier followed by re-modulation with a microwave local oscillator at the receiver. We demonstrate that by subsequently suppressing the optical carrier using a notch filter, the resulting optical signal can be directly detected to obtain a downconverted microwave signal.We further show that by simply controlling the amplitude of the microwave local oscillator, the system can be linearized to third-order, yielding an improvement in the dynamic range.

Treatment of death in the analysis of longitudinal studies of gerontological outcomes.

BACKGROUND: Longitudinal studies in gerontology are characterized by termination of measurement from death. Death is related to many important gerontological outcomes, such as functional disability, and may, over time, change the composition of an older study population. For these reasons, treating death as noninformative censoring of a longitudinal outcome may result in biased estimates of regression coefficients related to that outcome. METHODS: In a longitudinal study of community-living older persons, we analytically and graphically illustrate the dependence between death and functional disability. Relative to survivors, decedents display a rapid decline of functional ability in the months preceding death. Death's strong relationship with functional disability demonstrates that death is not independent of this outcome and, hence, leads to informative censoring. We also demonstrate the "healthy survivor effect" that results from death's selection effect, with respect to functional disability, on the longitudinal makeup of an older study population. RESULTS: We briefly survey commonly used approaches for longitudinal modeling of gerontological outcomes, with special emphasis on their treatment of death. Most common methods treat death as noninformative censoring. However, joint modeling methods are described that take into account any dependency between death and a longitudinal outcome. CONCLUSIONS: In longitudinal studies of older persons, death is often related to gerontological outcomes and, therefore, cannot be safely assumed to represent noninformative censoring. Such analyzes must account for the dependence between outcomes and death as well as the changing nature of the cohort.

Identifying Feasible Design Concepts for Products with Competing Performance Requirements by Metamodeling of Loss-Scaled Principal Components.

Engineering design often involves the determination of design variable settings to optimize competing performance requirements. In the early design stages we propose narrowing down the domain of design solutions using metamodels of principal components of the multiple performance levels that have been scaled by a multivariate quadratic loss function. The multivariate quadratic loss function is often used as the objective function in reaching optimal solutions because it utilizes the correlation structure of the design's performance metrics and penalizes off-target performance in a symmetrical manner. We also compare the computational performance of these loss-scaled principal components when used to solve for the design with minimal expected multivariate quadratic loss under three modeling approaches: response surface methodology, multivariate adaptive regression splines, and spatial point modeling. We demonstrate the technique on the design of the mechanical frame of an electric vehicle with six desired performance levels determined simultaneously by the dimensions of eight mechanical design elements. The method is the focus in this work.

Hierarchical models to evaluate translational research: Connecticut collaboration for fall prevention.

BACKGROUND AND OBJECTIVE: Evidence-based second stage translational studies are necessary and difficult to evaluate. A quasi-experimental design is used to compare the rate of fall-related health care utilization of two geographically disparate areas in Connecticut, a small state in the northeastern United States, to evaluate an intervention designed to reduce fall-related injuries among older persons. This evaluation examines the two years immediately prior to intervention. METHODS: The experimental units are postal (i.e., zip) code tabulation areas (ZCTAs) in which counts of fall-related health care utilization and demographic characteristics can be gathered from local and federal public health sources. We employ hierarchical modeling to determine whether there was a difference in fall-related health care utilization between the study arms prior to initiating the intervention. Geographic information systems are used to characterize neighboring ZCTAs and to graph model-adjusted rates of fall-related utilization. RESULTS: After adjustment for covariates and spatial variation, we observed no significant difference between rates or temporal trends of fall-related health care utilization in the study arms over the two year pre-intervention period. CONCLUSION: The study arms of the Connecticut Collaboration for Falls Prevention have equivalent rates and temporal trends of fall-related utilization over the two year pre-intervention period.

Ultrasensitive and high-dynamic-range two-photon absorption in a GaAs photomultiplier tube.

We demonstrate improved efficiency and dynamic range for two-photon absorption at 1.5 microm in a photoelectron-counting GaAs photomultiplier tube. cw laser measurements show pure two-photon absorption occurring in the device from average powers of 1.3 microW to nearly 1 mW. We use the detector to implement an autocorrelator with peak-power x average-power sensitivity of 1.7 x 10(-4) (mW)(2) and discuss practical ways to reduce this figure of merit to as low as 1 x 10(-5) (mW)(2).

Underwriting chronic renal failure.

The progression of chronic renal failure is quite variable. Equations to estimate the level of function are provided.

Goodpasture syndrome.

A case report of Goodpasture syndrome is described and discussed in terms of insurability.

Bilateral renal artery thrombotic occlusion: a unique complication following removal of a transthoracic intraaortic balloon.

An intraaortic balloon pump (IABP) was inserted through the ascending aorta during a coronary artery bypass operation. Five days later, after removal of the IABP and ligation of the end-to-side Dacron graft, the patient became acutely anuric. Abdominal aortography demonstrated a large "trapeze-shaped" thrombus which occluded both renal arteries. Following thrombectomy the patient recovered, with eventual return of renal function to the preoperative state.

Experimental renal infection: acute and chronic studies of histology and function.

Experimental renal infections have resulted in histologic lesions of acute and chronic pyelonephritis, but in most studies the urinary tract has been "traumatized" to induce persistent infection. Sequential functional alterations have been measured infrequently. The present studies were designed to separate the functional and histological changes caused by high pressure sterile reflux from reflux with pathogenic organisms. Reproducible disruption of the pelvic epithelium with extravasation of solution into the parenchyma and vasculature occurred with reflux of 2.0 ml of solution but not with 1.0 ml. Reflux with 2.0 ml of sterile broth failed to cause permanent histologic changes, but reflux with broth containing organisms resulted in minor inflammatory changes. There was no decrease in renal function in either group. In long-term studies, no histologic changes in the cortex or medulla were noted 21 weeks after reflux of 1.0 ml of broth containing organisms; however, there was failure of functional maturation in the infected animals commensurate with their growth, as compared to the shams and controls (P = 0.03). Sterile reflux did not cause cortical scars or changes in renal function, but persistent parenchymal infection was associated with arrest of functional growth.

Mitral valve replacement: a comparison of two prostheses.

Between November, 1965 and June, 1970, 175 patients underwent mitral valve replacement with the Smeloff-Cutter prosthesis (109 patients) or the toroidal valve (66 patients). The early mortality for patients with a toroidal mitral prosthesis was 18.2 percent (12 patients) and the late mortality 34.8 percent (23 patients). Among patients in whom Smeloff-Cutter mitral valves were inserted, the early mortality was 15.6 percent (17 patients) and the late mortality 23.9 percent (26 patients). During a follow-up period extending at least five years, thromboembolic complications occurred in 25.9 percent (14) of patients with toroidal valves and 7.6 percent (7) of patients with Smeloff-Cutter valves. Reoperation was necessary because of thrombosis of the prosthesis in seven patients with toroidal valves and two patients with Smeloff-Cutter valves. The incidence of endocarditis was the same in both groups. In this study, the Smeloff-Cutter mitral prosthesis proved to be superior to the toroidal valve because of a lower incidence of thromboembolism.