Effects of prolonged caloric stimulation upon oculomotor, vestibulospinal, and segmental spinal activity

Prolonged hot or cold stimulation effects on eye movements, vestibulospinal, and segmental spinal activities in monkey

Screening for Down's syndrome: effects, safety, and cost effectiveness of first and second trimester strategies commentary: rasults may not be widely applicable authors' response

Objective: To compare the effects, safety, and cost effectiveness of antenatal screening strategies for Down's syndrome. Design: Analysis of incremental cost effectiveness. Setting: United Kingdom. Main outcome measures: Number of liveborn babies with Down's syndrome, miscarriages due to chorionic villus sampling or amniocentesis, healthcare costs of screening programme, and additional costs and additional miscarriages per additional affected live birth prevented by adopting a more effective strategy. Results: Compared with no screening, the additional cost per additional liveborn baby with Down's syndrome prevented was £22 000 for measurement of nuchal translucency. The cost of the integrated test was £51 000 compared with measurement of nuchal translucency. All other strategies were more costly and less effective, or cost more per additional affected baby prevented. Depending on the cost of the screening test, the first trimester combined test and the quadruple test would also be cost effective options. Conclusions: The choice of screening strategy should be between the integrated test, first trimester combined test, quadruple test, or nuchal translucency measurement depending on how much service providers are willing to pay, the total budget available, and values on safety. Screening based on maternal age, the second trimester double test, and the first trimester serum test was less effective, less safe, and more costly than these four options

Multilevel network meta-regression for general likelihoods: synthesis of individual and aggregate data with applications to survival analysis

Network meta-analysis combines aggregate data (AgD) from multiple randomised controlled trials, assuming that any effect modifiers are balanced across populations. Individual patient data (IPD) meta-regression is the "gold standard" method to relax this assumption, however IPD are frequently only available in a subset of studies. Multilevel network meta-regression (ML-NMR) extends IPD meta-regression to incorporate AgD studies whilst avoiding aggregation bias, but currently requires the aggregate-level likelihood to have a known closed form. Notably, this prevents application to time-to-event outcomes. We extend ML-NMR to individual-level likelihoods of any form, by integrating the individual-level likelihood function over the AgD covariate distributions to obtain the respective marginal likelihood contributions. We illustrate with two examples of time-to-event outcomes, showing the performance of ML-NMR in a simulated comparison with little loss of precision from a full IPD analysis, and demonstrating flexible modelling of baseline hazards using cubic M-splines with synthetic data on newly diagnosed multiple myeloma. ML-NMR is a general method for synthesising individual and aggregate level data in networks of all sizes. Extension to general likelihoods, including for survival outcomes, greatly increases the applicability of the method. R and Stan code is provided, and the methods are implemented in the multinma R package.Comment: 43 pages, 8 figures (corrected metadata

Sensitivity Analysis for I-129 Wastes: Effect of Hydraulic Conductivity

Solid low-level radioactive wastes at the Savannah River Site (SRS) are disposed in trenches. In order to determine the permissible radioactive inventory limits for such disposal facilities, it is required to assess the behavior of radioactive waste material over long periods of time. The sensitivity of flow and I-129 (and similar radionuclides) transport in groundwater in the vadose zone to the hydraulic conductivities of the vadose zone subregions and the low-level waste is identified and quantified. A trench configuration and simulation model have been developed to analyze the flow and transport of the radionuclide in the vadose zone as it migrates to the groundwater table. The analysis identifies and quantifies the major dependencies of the flow and radionuclide fractional flux on the subregion hydraulic conductivities. Analysis results indicate the importance of the hydraulic conductivity assigned to the materials modeled, thereby providing the modeler and decision makers with valuable insights on the potential impact of the hydraulic conductivity on flow and radionuclide transport

Corridor-based functional performance measures correlate better with physical activity during daily life than treadmill measures in persons with peripheral arterial disease

ObjectiveTo compare associations of physical activity during daily life with treadmill walking performance and corridor-based functional performance measures in persons with lower extremity peripheral arterial disease (PAD).Study DesignCross-sectional.SubjectsOne hundred fifty-six men and women with PAD who completed baseline measurements and were randomized into the study to improve leg circulation (SILC) exercise clinical trial.Main Outcome MeasuresParticipants completed a Gardner-Skinner treadmill protocol. Corridor-based functional performance measures were the 6-minute walk, walking velocity over four meters at usual and fastest pace, and the short physical performance battery (SPPB) (0-12 scale, 12 = best). Physical activity during daily life was measured continuously over 7 days with a Caltrac (Muscle Dynamics Fitness Network, Inc, Torrence, Calif) accelerometer.ResultsAdjusting for age, gender, and race, higher levels of physical activity during daily life were associated with greater distance achieved in the 6-minute walk (P trend = .001), faster fast-paced four-meter walking velocity (P trend < .001), faster usual-paced four-meter walking speed (P trend = .027) and a higher SPPB (P trend = .005). The association of physical activity level with maximum treadmill walking distance did not reach statistical significance (P trend = .083). There were no associations of physical activity with treadmill distance to onset of leg symptoms (P trend = .795).ConclusionFunctional performance measures are more strongly associated with physical activity levels during daily life than treadmill walking measures

Randomized controlled trial of a primary care–based screening program to identify older women with prevalent osteoporotic vertebral fractures: Cohort for skeletal health in Bristol and Avon (COSHIBA)

Approximately 12% of postmenopausal women have osteoporotic vertebral fractures (VFs); these are associated with excess morbidity and mortality and a high risk of future osteoporotic fractures. Despite this, less than one-third come to clinical attention, partly due to lack of clear clinical triggers for referral for spinal radiographs. The aim of this study was to investigate whether a novel primary care–based screening tool could be used to identify postmenopausal women with osteoporotic VFs and increase appropriate management of osteoporosis. A randomized controlled trial was undertaken in 15 general practices within the Bristol area of the UK. A total of 3200 women aged 65 to 80 years were enrolled, with no exclusion criteria. A simple screening tool was carried out by a nurse in primary care to identify women at high risk of osteoporotic VFs. All identified high-risk women were offered a diagnostic thoracolumbar radiograph. Radiographs were reported using standard National Health Service (NHS) reporting, with results sent back to each participant's general practitioner (GP). Participants in the control arm did not receive the screening tool or radiographs. The main outcome measure was self-reported prescription of medication for osteoporosis at 6 months with a random 5% subsample verified against electronic GP records. Secondary outcome was self-reported incidence of new fractures. Results showed that allocation to screening increased prescription of osteoporosis medications by 124% (odds ratio [OR] for prescription 2.24 at 6 months; 95% confidence interval [CI], 1.16 to 4.33). Allocation to screening also reduced fracture incidence at 12-month follow-up (OR for new fracture 0.60; 95% CI, 0.35–1.03; p = 0.063), although this did not reach statistical significance. This study supports the use of a simple screening tool administered in primary care to increase appropriate prescription of medications for osteoporosis in postmenopausal women in the UK. © 2012 American Society for Bone and Mineral Researc

Recruiting participants with peripheral arterial disease for clinical trials: Experience from the Study to Improve Leg Circulation (SILC)

ObjectiveTo describe the success of diverse recruitment methods in a randomized controlled clinical trial of exercise in persons with peripheral arterial disease (PAD).MethodsAn analysis of recruitment sources conducted for the 746 men and women completing a baseline visit for the study to improve leg circulation (SILC), a randomized controlled trial of exercise for patients with PAD. For each recruitment source, we determined the number of randomized participants, the rate of randomization among those completing a baseline visit, and cost per randomized participant.ResultsOf the 746 individuals who completed a baseline visit, 156 were eligible and randomized. The most frequent sources of randomized participants were newspaper advertising (n = 67), mailed recruitment letters to patients with PAD identified at the study medical center (n = 25), and radio advertising (n = 18). Costs per randomized participant were $2750 for television advertising,$2167 for Life Line Screening, $2369 for newspaper advertising,$3931 for mailed postcards to older community dwelling men and women, and $5691 for radio advertising. Among those completing a baseline visit, randomization rates ranged from 10% for those identified from radio advertising to 32% for those identified from the Chicago Veterans Administration and 33% for those identified from posted flyers.ConclusionMost participants in a randomized controlled trial of exercise were recruited from newspaper advertising and mailed recruitment letters to patients with known PAD. The highest randomization rates after a baseline visit occurred among participants identified from posted flyers and mailed recruitment letters to PAD patients

Radiological consequences of a propagated fire accident in a radiochemical separations facility

A radiological consequence analysis of a propagated fire accident in a Savannah River Site (SRS) radiochemical separations facility has been performed. This analysis supports the safety documentation for the SRS plutonium reprocessing facility. Included are the evaluation of the doses resulting from the exposure to the radioactive airborne release for co-located facility worker and the off-site individual receptors. Atmospheric dispersion calculations using qualified five-year (1987-1991) meteorological data were performed with the computer code AXAIR89Q, a validated computer code for radiological dose calculations. Radioactive source term estimates and assumptions of material composition and isotope distribution were based on existing permissible storage levels as defined in approved safety documentation. The fire accident scenario assumes that the fire propagates in the entire facility on four structural levels. Approximately 97% of the radioactive materials released occurs from levels three and four of the facility, which are not included in the ventilation pathway to the sand trap filter. Radiological analysis results indicate that the doses to co-located worker and off-site individual receptors are equal to 4.4 rem and 3.3 rem, respectively. Accident mitigators that were identified include provision for filtration capacity from levels three and four of the facility, and relocation of stored radioactive materials. Provision for filtration capacity would reduce the source term from an unfiltered activity of 53.6 Ci to a filtered activity of 2.0 Ci. Relocation of stored radioactive materials would result in a source term reduction from 53.6 Ci to 20 Ci. Limitations exist, however, that may make implementation of the identified mitigators difficult or prohibitive

Bayesian evidence synthesis for a transmission dynamic model for HIV among men who have sex with men

Understanding infectious disease dynamics and the effect on prevalence and incidence is crucial for public health policies. Disease incidence and prevalence are typically not observed directly and increasingly are estimated through the synthesis of indirect information from multiple data sources. We demonstrate how an evidence synthesis approach to the estimation of human immunodeficiency virus (HIV) prevalence in England and Wales can be extended to infer the underlying HIV incidence. Diverse time series of data can be used to obtain yearly “snapshots” (with associated uncertainty) of the proportion of the population in 4 compartments: not at risk, susceptible, HIV positive but undiagnosed, and diagnosed HIV positive. A multistate model for the infection and diagnosis processes is then formulated by expressing the changes in these proportions by a system of differential equations. By parameterizing incidence in terms of prevalence and contact rates, HIV transmission is further modeled. Use of additional data or prior information on demographics, risk behavior change and contact parameters allows simultaneous estimation of the transition rates, compartment prevalences, contact rates, and transmission probabilities