Stability of nocturnal wake and sleep stages defines central nervous system disorders of hypersomnolence.

Study Objectives: We determine if young people with narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), and idiopathic hypersomnia (IH) have distinct nocturnal sleep stability phenotypes compared to subjectively sleepy controls.

Methods: Participants were 5- to 21-year old and drug-naïve or drug free: NT1 (n = 46), NT2 (n = 12), IH (n = 18), and subjectively sleepy controls (n = 48). We compared the following sleep stability measures from polysomnogram recording between each hypersomnolence disorder to subjectively sleepy controls: number of wake and sleep stage bouts, Kaplan-Meier survival curves for wake and sleep stages, and median bout durations.

Demystifying Fisher Information: What Observation Data Reveal about Our Models.

Information theory is the basis for understanding how information is transmitted as observations. Observation data can be used to compare uncertainty on parameter estimates and predictions between models. Jacobian Information (JI) is quantified as the determinant of the weighted Jacobian (sensitivity) matrix.

Developmental Changes in Ultradian Sleep Cycles across Early Childhood.

Nocturnal human sleep is composed of cycles between rapid eye movement (REM) sleep and non-REM (NREM) sleep. In adults, the structure of ultradian cycles between NREM and REM sleep is well characterized; however, less is known about the developmental trajectories of ultradian sleep cycles across early childhood. Cross-sectional studies indicate that the rapid ultradian cycling of active-quiet sleep in infancy shifts to a more adult-like pattern of NREM-REM sleep cycling by the school-age years, yet longitudinal studies elucidating the details of this transition are scarce.

Progressive Loss of the Orexin Neurons Reveals Dual Effects on Wakefulness.

Study Objectives: Narcolepsy is caused by loss of the orexin (also known as hypocretin) neurons. In addition to the orexin peptides, these neurons release additional neurotransmitters, which may produce complex effects on sleep/wake behavior. Currently, it remains unknown whether the orexin neurons promote the initiation as well as the maintenance of wakefulness, and whether the orexin neurons influence initiation or maintenance of sleep.

Disturbance and temporal partitioning of the activated sludge metacommunity.

The resilience of microbial communities to press disturbances and whether ecosystem function is governed by microbial composition or by the environment have not been empirically tested. To address these issues, a whole-ecosystem manipulation was performed in a full-scale activated sludge wastewater treatment plant. The parameter solids retention time (SRT) was used to manipulate microbial composition, which started at 30 days, then decreased to 12 and 3 days, before operation was restored to starting conditions (30-day SRT).

Errors in coarse particulate matter mass concentrations and spatiotemporal characteristics when using subtraction estimation methods.

In studies of coarse particulate matter (PM10-2.5), mass concentrations are often estimated through the subtraction of PM2.5 from collocated PM10 tapered element oscillating microbalance (TEOM) measurements.

Assessing the impact of a wood stove replacement program on air quality and children's health.

Many rural mountain valley communities experience elevated ambient levels of fine particulate matter (PM*) in the winter, because of contributions from residential wood-burning appliances and sustained temperature inversion periods during the cold season. A wood stove change-out program was implemented in a community heavily affected by wood-smoke-derived PM2.5 (PM < or = 2.

Residential indoor PM2.5 in wood stove homes: follow-up of the Libby changeout program.

Unlabelled: In 2005 through 2008, a small rural mountain valley community engaged in a woodstove changeout program to address concerns of poor ambient air quality. During this program, we assessed changes to indoor air quality before and after the introduction of a new, lower emission woodstove. We previously reported a >70% reduction in indoor PM(2.

A rural community intervention targeting biomass combustion sources: effects on air quality and reporting of children's respiratory outcomes.

Objective: Improvements in urban air quality are largely driven by controls on industrial and mobile source emissions, but such factors may have limited influence on many rural environments where biomass combustion (eg, wood stoves) serves as the primary source of fine particulate matter (PM(2.5)). The authors tracked changes in children's respiratory health during a wood stove intervention in a rural mountain valley community heavily impacted by wood smoke-derived PM(2.

On the correlation between single-frequency impedance measurements and human skin permeability to water.

The objective of this study was to quantitatively compare measurements of tritiated water permeability with impedance determined at either 100 or 1000 Hz using an LCR databridge on the same pieces of skin. A previously published expression based on a simple circuit of a parallel resistor and constant phase element (CPE) was used to relate (RPARA) measured at different frequencies to the DC resistance (RskinA) and the steady-state skin permeability of tritiated water (kp). Using this analysis, kp and (RPARA) data from three laboratories were shown to be consistent with each other, and kp and (RskinA) estimated from (RPARA) were linearly correlated.

Community woodstove changeout and impact on ambient concentrations of polycyclic aromatic hydrocarbons and phenolics.

A large woodstove changeout program was carried out in Libby, Montana, with the goal of reducing ambient levels of PM2.5. This provided researchers the opportunity to measure ambient concentrations of phenolic and polycyclic aromatic hydrocarbons (PAHs) before, during, and after the changeout of nearly 1200 stoves to evaluate the effectiveness of the intervention.

Improved bioequivalence assessment of topical dermatological drug products using dermatopharmacokinetics.

Purpose: A dermatopharmacokinetic (DPK) approach, in which drug levels in the stratum corneum (SC) are measured as a function of time post-application and post-removal of the product using tape-strip sampling in vivo in humans, has been considered for the comparative assessment of topical bioavailability. Its application to-date has been limited by contradictory results and concerns that variability in the method necessitates large numbers of treatment sites and volunteers. The objective of this study was to test whether a revised protocol could better assess bioequivalence.

Determining bioequivalence of topical dermatological drug products by tape-stripping.

The maximum level of drug in the stratum corneum (C(max)) and the area under the curve of drug level in the stratum corneum versus time (AUC) have been proposed as metrics for assessing bioequivalence of topical drugs. These metrics, which require that concentrations be measured at eight or more times, were developed for drugs that are absorbed into the bloodstream, and are less appropriate for topical drugs. Concentrations of topical drugs are measured by tape-stripping, and it is difficult to make a large number of precise measurements due to the limited amount of available skin.

Optimizing metrics for the assessment of bioequivalence between topical drug products.

Purpose: Stratum corneum tape stripping post-application of a drug product followed by analysis of the active agent in this tissue layer is an approach being seriously considered for the comparative assessment of topical bioavailability. Key issues revolve around how best to perform this experiment and interpret the data.

Methods: Using previously published results from a comparative study of three 0.

Lung cancer and internal lung doses among plutonium workers at the Rocky Flats Plant: a case-control study.

The authors conducted a nested case-control study of the association between lung cancer mortality and cumulative internal lung doses among a cohort of workers employed at the Rocky Flats Plant in Colorado from 1951 to 1989. Cases (n = 180) were individually matched with controls (n = 720) on age, sex, and birth year. Annual doses to the lung from plutonium, americium, and uranium isotopes were calculated for each worker with an internal dosimetry model.

Uncertainty in measurements of dermal absorption of pesticides.

Dermal absorption experiments form an important component in the assessment of risk from exposure to pesticides and other substances. Much dermal absorption data is gathered in rat experiments carried out using a certain standard protocol. Uncertainties in these data arise from many sources and can be quite large.

The observed human sperm mutation frequency cannot explain the achondroplasia paternal age effect.

The lifelong spermatogonial stem cell divisions unique to male germ cell production are thought to contribute to a higher mutation frequency in males. The fact that certain de novo human genetic conditions (e.g.

Risk set sampling for case-crossover designs.

In the case-crossover design, only cases are sampled, and effect estimates are based on within-subject comparisons of exposures at failure times with exposures at control times. Sampling control times appropriately can provide some control for unmeasured confounding, but may introduce bias owing to time trends in the exposure of interest. The theory of risk set sampling (Borgan Ø, Goldstein L, Langholz B.

Unequal exchange at the Charcot-Marie-Tooth disease type 1A recombination hot-spot is not elevated above the genome average rate.

An increasing number of human diseases and syndromes are being found to result from micro-duplications or microdeletions arising from meiotic recombination between homologous repeats on the same chromosome. The first microduplication syndrome delineated, Charcot-Marie-Tooth disease type 1A (CMT1A), results from unequal crossing over between two >98% identical 24 kb repeats (CMT1A-REPs) on chromosome 17. In addition to its medical significance, the CMT1A region has features that make it a unique resource for detailed analysis of human unequal recombination.

Statistical methods for epidemiologic studies of the health effects of air pollution.

We describe two statistical designs that can provide efficient estimates of the health effects of exposure to air pollutants in epidemiologic studies. We also evaluate the effects of measurement error in exposure assessment on the accuracy of estimated health effects. The bidirectional case-crossover design is a variant of a method proposed by Maclure (1991).

A study of twelve Southern California communities with differing levels and types of air pollution. II. Effects on pulmonary function.

To study the possible chronic respiratory effects of air pollutants, we designed and initiated a 10-yr prospective study of Southern California public schoolchildren living in 12 communities with different levels and profiles of air pollution. The design of the study, exposure assessment methods, and survey methods and results related to respiratory symptoms and conditions are described in the accompanying paper. Pulmonary function tests were completed on 3,293 subjects.

A study of twelve Southern California communities with differing levels and types of air pollution. I. Prevalence of respiratory morbidity.

To study possible chronic respiratory effects of air pollutants, we initiated a 10-yr prospective cohort study of Southern California children, with a study design focused on four pollutants: ozone, particulate matter, acids, and nitrogen dioxide (NO2). Twelve demographically similar communities were selected on the basis of historic monitoring information to represent extremes of exposure to one or more pollutants. In each community, about 150 public school students in grade 4, 75 in grade 7, and 75 in grade 10 were enrolled through their classrooms.

Acute effects of ambient ozone on asthmatic, wheezy, and healthy children.

Southern California children (10 to 12 years old) participated in a two-season study to assess the potential acute respiratory effects of ambient ozone (O3). Asthmatic (n = 49), wheezy (n = 53), and healthy (n = 93) children completed a four-day (Friday through Monday) study protocol, once in spring and again in summer, that included the use of daily activity and symptom diaries, heart rate recording devices, personal O3 samplers, and maximal effort spirometry several times per day. Data from regional monitoring stations were used to establish ambient hourly O3 concentrations.

Bidirectional case-crossover designs for exposures with time trends.

In the case-crossover design (Maclure, 1991, American Journal of Epidemiology 133, 144-153), only cases are sampled, and risk estimates are based on within-subject comparisons of exposures at failure times with exposures at times prior to failure, using matched case-control methods. While the design provides considerable advantages, unidirectional retrospective control sampling (selecting control times only prior to failure) can cause risk estimates to be confounded by time trends in exposure. However, when subsequent exposures are not influenced by failures, as in studies of environmental exposures such as air pollutants, it is possible to determine at times postfailure what a subject's level of exposure would have been had the subject not failed.

Genetic polymorphism of CYP2D6 and lung cancer risk in African-Americans and Caucasians in Los Angeles County.

The well described genetic polymorphism of the CYP2D6 gene influences response to a wide variety of therapeutic agents metabolized by the CYP2D6 enzyme product. CYP2D6 also appears to play a role, along with other cytochrome P450 enzymes, in the metabolic activation of the tobacco specific nitrosamine, NNK, as well as metabolism of nicotine to cotinine. While impaired activity of CYP2D6 was strongly protective against lung cancer in some studies, primarily based on phenotyping, the literature is conflicting.