Power, Validity, Bias and Robustness of Family-based Association Analysis Methods in the Presence of Linkage for Late Onset Diseases

This simulation-based report compares the performance of five methods of association analysis in the presence of linkage using extended sibships: the Family-Based Association Test (FBAT), Empirical Variance FBAT (EV-FBAT), Conditional Logistic Regression (CLR), Robust CLR (R-CLR) and Sibship Disequilibrium Test (SDT). The two tests accounting for residual familial correlation (EV-FBAT and R-CLR) and the model-free SDT showed correct test size in all simulated designs, while FBAT and CLR were only valid for small effect sizes. SDT had the lowest power, while CLR had the highest power, generally similar to FBAT and the robust variance analogues. The power of all model-dependent tests dropped when the model was misspecified, although often not substantially. Estimates of genetic effect with CLR and R-CLR were unbiased when the disease locus was analysed but biased when a nearby marker was analysed. This study demonstrates that the genetic effect does not need to be extreme to invalidate tests that ignore familial correlation and confirms that analogous methods using robust variance estimation provide a valid alternative at little cost to power. Overall R-CLR is the best-performing method among these alternatives for the analysis of extended sibship data

A compilation of observations from moored current meters and thermographs. Vol. 1. Oregon continental shelf, July 1965-February 1966

This is the first data report of a program designed to study physical processes in Oregon shelf waters by means of moored instrument arrays. Various statistics and plots of smoothed data are presented for time series of current velocity and of temperature. Data were collected in July, August, September, and October of 1965 and in January and February of 1966

Combined effects of heat waves and droughts on avian communities across the conterminous United States

Increasing surface temperatures and climatic variability associated with global climate change are expected to produce more frequent and intense heat waves and droughts in many parts of the world. Our goal was to elucidate the fundamental, but poorly understood, effects of these extreme weather events on avian communities across the conterminous United States. Specifically, we explored: (1) the effects of timing and duration of heat and drought events, (2) the effects of jointly occurring drought and heat waves relative to these events occurring in isolation, and (3) how effects vary among functional groups related to nest location and migratory habit, and among ecoregions with differing precipitation and temperature regimes. Using data from remote sensing, meteorological stations, and the North American Breeding Bird Survey, we used mixed effects models to quantify responses of overall and functional group abundance to heat waves and droughts (occurring alone or in concert) at two key periods in the annual cycle of birds: breeding and post-fledging. We also compared responses among species with different migratory and nesting characteristics, and among 17 ecoregions of the conterminous United States. We found large changes in avian abundances related to 100-year extreme weather events occurring in both breeding and post-fledging periods, but little support for an interaction among time periods. We also found that jointly-, rather than individually-occurring heat waves and droughts were both more common and more predictive of abundance changes. Declining abundance was the only significant response to post-fledging events, while responses to breeding period events were larger but could be positive or negative. Negative responses were especially frequent in the western U.S., and among ground-nesting birds and Neotropical migrants, with the largest single-season declines (36%) occurring among ground-nesting birds in the desert Southwest. These results indicate the importance of functional traits, timing, and geography in determining avian responses to weather extremes. Because dispersal to other regions appears to be an important avian response, it may be essential to maintain habitat refugia in a more climatically variable future

Effects of drought on avian community structure

Droughts are expected to become more frequent under global climate change. Avifauna depend on precipitation for hydration, cover, and food. While there are indications that avian communities respond negatively to drought, little is known about the response of birds with differing functional and behavioral traits, what time periods and indicators of drought are most relevant, or how response varies geographically at broad spatial scales. Our goals were thus to determine (1) how avian abundance and species richness are related to drought, (2) whether community variations are more related to vegetation vigor or precipitation deviations and at what time periods relationships were strongest, (3) how response varies among avian guilds, and (4) how response varies among ecoregions with different precipitation regimes. Using mixed effect models and 1989–2005 North American Breeding Bird Survey data over the central United States, we examined the response to 10 precipitation- and greenness based metrics by abundance and species richness of the avian community overall, and of four behavioral guilds. Drought was associated with the most negative impacts on avifauna in the semiarid Great Plains, while positive responses were observed in montane areas. Our models predict that in the plains, Neotropical migrants respond the most negatively to extreme drought, decreasing by 13.2% and 6.0% in abundance and richness, while permanent resident abundance and richness increase by 11.5% and 3.6%, respectively in montane areas. In most cases, response of abundance was greater than richness and models based on precipitation metrics spanning 32-week time periods were more supported than those covering shorter time periods and those based on greenness. While drought is but one of myriad environmental variations birds encounter, our results indicate that drought is capable of imposing sizable shifts in abundance, richness, and composition on avian communities, an important implication of a more climatically variable future

Assessment of urinary 6-oxo-pipecolic acid as a biomarker for ALDH7A1 deficiency

ALDH7A1 deficiency is an epileptic encephalopathy whose seizures respond to treatment with supraphysiological doses of pyridoxine. It arises as a result of damaging variants in ALDH7A1, a gene in the lysine catabolism pathway. α-Aminoadipic semialdehyde (α-AASA) and Δ1-piperideine-6-carboxylate (P6C), which accumulate because of the block in the lysine pathway, are diagnostic biomarkers for this disorder. Recently, it has been reported that 6-oxo-pipecolic acid (6-oxo-PIP) also accumulates in the urine, CSF and plasma of ALDH7A1-deficient individuals and that, given its improved stability, it may be a more suitable biomarker for this disorder. This study measured 6-oxo-PIP in urine from a cohort of 30 patients where α-AASA was elevated and showed that it was above the normal range in all those above 6 months of age. However, 6-oxo-PIP levels were within the normal range in 33% of the patients below 6 months of age. Levels increased with age and correlated with a decrease in α-AASA levels. Longitudinal analysis of urine samples from ALDH7A1-deficient patients who were on a lysine restricted diet whilst receiving supraphysiological doses of pyridoxine showed that levels of 6-oxo-PIP remained elevated whilst α-AASA decreased. Similar to α-AASA, we found that elevated urinary excretion of 6-oxo-PIP can also occur in individuals with molybdenum cofactor deficiency. This study demonstrates that urinary 6-oxo-PIP may not be a suitable biomarker for ALDH7A1 deficiency in neonates. However, further studies are needed to understand the biochemistry leading to its accumulation and its potential long-term side effects

Hoof Matters: Developing an Athletic Thoroughbred Hoof

Conformation of the hooves and distal limbs of foals and factors influencing their morphological development have not been reported in detail for the Thoroughbred breed. In this paper we explore morphogenesis of the equine distal limb in Thoroughbred foals with emphasis on adaptations in response to weight bearing early in life that prepare the foal for an athletic career. Novel data from four studies are presented chronologically during key time periods to illustrate specific aspects of distal limb growth and adaptation. Dorsal epidermal thickness increased from 2.84 ± 0.41 mm in utero to 4.04 ± 1.10 mm by 4 months of age. The increase in thickness was accompanied by decreased tubular density, increased inter-tubular material, and an increase in number and size of tubules at the quarters, which provided a malleable hoof capsule to allow for skeletal growth. Between 4–6 months of age, the hoof widens, and higher loading on the medial side (>60%) vs. the lateral side (<40%) may be factors that influence mature asymmetric hoof shape. Shortly after 12 months-of-age, the dorsal hoof wall angle and dorsal parietal angle of the distal phalanx become parallel, thus optimizing the functional capacity of the hoof capsule in the weanling Thoroughbred

Crew factors in flight operations 2: Psychophysiological responses to short-haul air transport operations

Seventy-four pilots were monitored before, during, and after 3- or 4-day commercial short-haul trip patterns. The trips studied averaged 10.6 hr of duty per day with 4.5 hr of flight time and 5.5 flight segments. The mean rest period lasted 12.5 hr and occurred progressively earlier across successive days. On trip nights, subjects took longer to fall asleep, slept less, woke earlier, and reported lighter, poorer sleep with more awakenings than on pretrip nights. During layovers, subjective fatigue and negative affect were higher, and positive affect and activation lower, than during pretrip, in-flight, or posttrip. Pilots consumed more caffeine, alcohol, and snacks on trip days than either pretrip or posttrip. Increases in heart rate over mid-cruise were observed during descent and landing, and were greater for the pilot flying. Heart-rate increases were greater during takeoff and descent under instrument meteorological conditions (IMC) than under visual meteorological conditions (VMC). The following would be expected to reduce fatigue in short-haul operations: regulating duty hours, as well as flight hours; scheduling rest periods to begin at the same time of day, or progressively later, across the days of a trip; and educating pilots about alternatives to alcohol as a means of relaxing before sleep