bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exome Analysis of a Family With Pleiotropic Congenital Heart Disease
Authors: Arrington Cammon B. , Bleyl Steven B. , Matsunami Norisada , Bonnell Gabriel D. , Otterud Brith E.M. , Nielsen Douglas C. , Stevens Jeffrey , Levy Shawn , Leppert Mark F. , Bowles Neil E. 
Published: February 2012

Background—
A number of single gene defects have been identified in patients with isolated or nonsyndromic congenital heart defects (CHDs). However, due to significant genetic heterogeneity, candidate gene approaches have had limited success in finding high-risk alleles in most cases. The purpose of this study was to use exome sequencing to identify high-risk gene variants in a family with highly penetrant pleiotropic CHD.

Methods and Results—
DNA samples from 2 members of a family with diverse CHD were analyzed by exome sequencing. Variants were filtered to eliminate common variants and sequencing artifacts and then prioritized based on the predicted effect of the variant and on gene function. The remainder of the family was screened using polymerase chain reaction, high-resolution melting analysis, and DNA sequencing to evaluate variant segregation. After filtering, >2000 rare variants (including single nucleotide substitutions and indels) were shared by the 2 individuals. Of these, 46 were nonsynonymous, 3 were predicted to alter splicing, and 6 resulted in a frameshift. Prioritization reduced the number of variants potentially involved in CHD to 18. None of the variants completely segregated with CHD in the kindred. However, 1 variant, Myh6 Ala290Pro, was identified in all but 1 affected individual. This variant was previously identified in a patient with tricuspid atresia and large secundum atrial septal defect.

Conclusions—
It is likely that next-generation sequencing will become the method of choice for unraveling the complex genetics of CHD, but information gained by analysis of transmission through families will be crucial.
An Estimate of Structural Uncertainty in QuikSCAT Wind Vector Retrievals
Authors: Fangohr Susanne , Kent Elizabeth C. 
Published: February 2012

AbstractDifferences between Quick Scatterometer (QuikSCAT) level-2b wind vectors from the Jet Propulsion Laboratory [JPL; the Direction Interval Retrieval with Thresholded Nudging (DIRTH) product] and from the Remote Sensing Systems Co. (RSS; smoothed versions 3.0 and 4.0) for one sample month are presented. Each dataset is derived from the same observations, but processing methods result in differences between wind vectors. These differences originate from 1) uncertainty in the geophysical model functions that relate backscatter to wind, 2) noise in the backscatter measurements, and 3) spatial filtering. Statistics of wind vector differences from RSS and JPL are used as an indication of structural uncertainty in QuikSCAT wind retrievals. When grouped by 1 m s−1bins, systematic differences are largest beyond 20 m s−1, where wind speeds from version 3.0 (version 4.0) of RSS can be more than 15 (10) m s−1higher (lower) than JPL wind speeds. Below 20 m s−1, systematic differences on the order of tenths of a meter per second are attributed to differences in the retrieval methods, rain and ice contamination, and cross-swath position. Even once the recommended data flags are applied, differences in individual wind speed retrievals exceed 10 m s−1in a few cases but are much smaller in regions of the swath for which the viewing geometry allows more reliable retrievals. In all parts of the swath, the standard deviations of the differences are smaller than 1.0 m s−1. The analyses provide a measure of the structural uncertainty in QuikSCAT wind velocity that is due to the retrieval process, although such comparisons are not able to determine which dataset is closest to the actual wind.
Measurement and Statistical Modeling of the Urban Heat Island of the City of Utrecht (the Netherlands)
Authors: Brandsma Theo , Wolters Dirk 
Published: February 2012

AbstractMobile temperature and humidity measurements have been performed along a 14-km transect through the city of Utrecht, in the Netherlands (311 000 inhabitants), during the period March 2006–January 2009. The measurements took place on a bicycle during commuter traffic and resulted in 106 nighttime profiles (before sunrise) and 77 daytime (afternoon) profiles. It is shown how the intensity of the urban heat island depends on wind direction, cloudiness, and wind speed. Statistical models are constructed that relate the mean and maximum nighttime urban heat island intensity profiles to area-averaged sky-view factors and land use combined at both the micro- and local scales. Sky-view factors are estimated from a 0.5 m × 0.5 m surface elevation database, and land use is obtained from a 25 m × 25 m land-use database. The models are calibrated using the mobile measurements and provide estimates of the spatial distribution of the mean and maximum nighttime urban heat island intensity in Utrecht. Both models explain more than 75% of the variance. A separate nonlinear model is introduced that relates the temperature differences between the warmest part and coolest part of the transects to wind speed and cloudiness.
Test of the Fixed Anvil Temperature Hypothesis
Authors: Li Yue , Yang Ping , North Gerald R. , Dessler Andrew 
Published: February 2012

Abstract
The fixed anvil temperature (FAT) hypothesis is examined based on the Aqua Moderate Resolution Imaging Spectroradiometer (MODIS)-based cloud-top temperature (CTT) in conjunction with the tropical atmospheric profiles and sea surface temperature (SST) from the European Centre for Medium-Range Weather Forecasts (ECMWF) Interim Reanalysis. Consistent with the physical governing mechanism of the FAT hypothesis, the peak clear-sky diabatic subsidence and convergence profiles are located at roughly the same level (200 hPa) as the peak in the cloud profile, which is fundamentally determined by the rapid decrease of water vapor concentration above this level. The geographical maxima of cloud fraction agree well with those of water vapor, clear-sky cooling rates, and diabatic convergence at 200 hPa. The use of direct CTT measurements suggests the CTT in specific Pacific basins exhibit different characteristics as the frequency distribution of the tropical SST varies from boreal winter to summer. When averaging over the tropics as a whole, the CTT distributions are approximately unchanged primarily because of cancellation by the variations associated with individual regions. An analysis of the response of the tropical mean CTT anomaly time series to the SST indicates that a possible negative relationship is present, whereas the relationship tends to be positive over the tropical western Pacific and Indian Oceans. In addition, it is suggested to interpret the FAT hypothesis, and the more recent proportionately higher anvil temperature (PHAT) hypothesis, by using the temperature at the maximum cloud detrainment level instead of the CTT.
Quantifying Dispersal and Connectivity of Surface Waters Using Observational Lagrangian Measurements
Authors: Piecuch Christopher G. , Rynearson Tatiana A. 
Published: February 2012

Abstract
Probability distribution functions of displacement are central to Lagrangian statistics and the study of fluid dispersal. A method for computing marginal probability distributions of passive tracer dispersal from Lagrangian observations is developed. Using a pseudotrack approach, probability distributions for the domain of occupation and transit time are developed, complimenting more frequently used bulk statistics for average transit time and overall crossing probability. To demonstrate application of this technique to observations, likelihoods and time scales of dispersal from the Gulf Stream to the Azores are quantified using World Ocean Circulation Experiment (WOCE) Surface Velocity Program (SVP) near-surface drifter data for the years 1992–2008. Over observable time scales, the transit of a particle in the near-surface ocean from the Gulf Stream to the Azores occurs across a spectrum of time scales, from tens to hundreds of days, with an overall likelihood of 42% ± 4% and a mean time scale of 321 ± 41 days. The exclusion of measurements from drifters released after 1 January 2004 (which have been shown to potentially exhibit bias) slightly increases the overall likelihood of connection (49% ± 6%), consistent with recent surface current shifts in the northern North Atlantic, and increases the mean connection time scale (371 ± 52 days), potentially reflecting spurious acceleration of drifters in recent years. The method presented is general and applicable to a wide range of applications in physical and ecological oceanography.
The Pharmacokinetics and Pharmacodynamics of Zaleplon Delivered as a Thermally Generated Aerosol in a Single Breath to Volunteers
Authors: Avram Michael J. , Spyker Daniel A. , Kehne John H. , Cassella James V. 
Published: February 2012

AbstractPharmacokinetics, pharmacodynamics, safety, and tolerability of inhaled zaleplon were assessed in healthy volunteers. Forty participants received 0.5, 1, 2, or 4 mg zaleplon or placebo as a thermally generated aerosol in a randomized, double‐blind, parallel‐group, dose escalation study. Blood was collected up to 24 hours after dosing, and sedation was assessed up to 8 hours. Following inhalation, the observed median time to maximum plasma concentrations (25%, 75%) was 1.89 (1.45, 3.08) minutes and the mean (SD) elimination half‐life was 1.24 (0.24) hours. The equilibration half‐life for sedation (t1/2ke0) was 1.16 (0.62, 2.17) minutes. The zaleplon AUC was dose proportional across doses, with a slope (90% confidence interval) of log‐AUC versus log‐dose of 0.92 (0.82, 1.02). No clinically significant changes were noted in laboratory values, vital signs, or spirometry. The most common adverse events were dizziness, somnolence, euphoria, headache, and visual disturbance. Zaleplon inhalation represents a safe, well‐tolerated means of rapidly achieving effective plasma concentrations.
Exposure‐Exposure Relationship of Tocilizumab, an Anti–IL‐6 Receptor Monoclonal Antibody, in a Large Population of Patients With Rheumatoid Arthritis
Authors: Levi Micha , Grange Susan , Frey Nicolas 
Published: February 2012

AbstractRelationships between tocilizumab exposure and response were evaluated using data from 4 phase III studies. Increased tocilizumab exposure was associated with improvements in Disease Activity Score using 28 joints (DAS28) and American College of Rheumatology (ACR) criteria and with a decrease in inflammation markers. A population pharmacokinetic/pharmacodynamic (PKPD) model was developed to describe data from 2 studies. An indirect‐response model with a sigmoid Emax (maximal drug effect) inhibitory drug effect on DAS28 “production” rate adequately described the relationship between tocilizumab concentration and DAS28. Mean minimum serum tocilizumab concentration at steady state was greater than the EC50 (concentration at which 50% of Emax on DAS28 is reached) with the 8‐mg/kg dose but not with the 4‐mg/kgdose. Simulations within a large rheumatoid arthritis (RA) population showed that DAS remission rates were 38% for 8 mg/kg and 24% for 4 mg/kg. Tocilizumab was more potent in RA patients with higher baseline interleukin‐6 levels, but this effect was not clinically significant. Other covariates (eg, presence of neutralizing antitocilizumab antibodies) did not demonstrate a clinically meaningful effect on tocilizumab DAS28 dose‐response relationships. These data support clinical observations that tocilizumab 8 mg/kg is more effective than 4 mg/kg in reducing disease activity.
A 7‐Year Review of the Safety of Tonsillectomy during Short‐Term Medical Mission Trips
Authors: Sykes Kevin J. , Le Phong T. , Sale Keith A. , Nicklaus Pamela J. 
Published: February 2012

ObjectiveTo evaluate the safety of tonsillectomy in a short‐term medical mission setting.Study DesignRetrospective chart review.SettingCatholic mission hospital in Guatemala.Subjects and MethodsDuring 7 consecutive annual mission trips from 2004 to 2010, patients received tonsillectomy and adenotonsillectomy. Established safety protocol requires candidates for tonsillectomy to agree to stay within 1 hour of the hospital for 10 days following the operation. This study includes all tonsillectomy patients regardless of age or indication for tonsillectomy. The primary outcome measures include posttonsillectomy hemorrhage, nasopharyngeal reflux, readmission for dehydration, and mortality. This is a novel study as the work performed by most short‐term medical missions is unregulated and unevaluated.ResultsMedical charts were available for 197 (96.6%) of the 204 patients receiving tonsillectomy in the 7‐year period; this was the only inclusion criterion. Ninety‐nine (50.3%) patients had tonsillectomy concomitantly with adenoidectomy. Patients ranged in age from 3 to 66 years. The mean (SD) age was 17.2 (14.0) years. The study team found documentation of postoperative complications in 3 (1.5%) patients; 2 experienced postoperative hemorrhage, 1 within the first postoperative hour and 1 at 96 hours. The final patient returned to the hospital within 24 hours symptomatic for dehydration.ConclusionsThe authors have evaluated a protocol for tonsillectomy patients in a specific setting and believe their data represent satisfactory outcomes for the reviewed patients. The generalizability of this information is uncertain, but safety protocols should be established on all short‐term medical missions to prevent untoward complications.
Cluster headache shows no association with rapid eye movement sleep
Authors: Zaremba Sebastian , Holle Dagny , Wessendorf Thomas E , Diener Hans C , Katsarava Zaza , Obermann Mark 
Published: February 2012

Background: The connection of cluster headache (CH) attacks with rapid eye movement (REM) sleep has been suggested by various studies, while other authors challenge this assumption. We performed serial polysomnography to determine the association of nocturnal CH attacks and sleep. Methods: Five patients diagnosed with CH (two with the episodic and three with the chronic subtype) were included and studied over four consecutive nights to evaluate connections between attacks onset and sleep stage. Results: Twenty typical CH attacks were reported. Thirteen of these attacks arose from sleep. Seven attacks were reported after waking in the morning or shortly before going to sleep. The beginnings of sleep-related attacks were distributed arbitrarily between different non-REM sleep stages. No association of CH attacks with REM or sleep disordered breathing was observed. Increased heart rate temporally associated with transition from one sleep state to another was observed before patients awoke with headache. Total sleep time, total wake time, arousal index and distribution of non-REM sleep stages were different between chronic and episodic CH. Conclusion: CH attacks are not associated with REM sleep. Brain regions involved in sleep stage transition might be involved in pathophysiology of CH. Differences in sleep characteristics between subgroups might indicate adaptation processes or underlying pathophysiology.
The Prevalence of Radiographic Hip Abnormalities in Elite Soccer Players
Authors: Gerhardt Michael B. , Romero Alex A. , Silvers Holly Jacinda , Harris David J. , Watanabe Diane , Mandelbaum Bert R. 
Published: February 2012

Background: Hip injuries, both intra- and extra-articular, are becoming a more commonly recognized, diagnosed, and treated injury in athletes of all competitive levels. Our goal is to establish a previously undefined value in this athletic population—the prevalence of radiographic hip abnormalities in elite soccer athletes. Purpose: To provide a foundation for the future body of literature regarding hip pathologic abnormalities and “at-risk” hips in athletes of all ages and levels of participation. Study Design: Descriptive epidemiology study. Methods: We retrospectively reviewed the anteroposterior pelvis and frog-leg lateral radiographs of 95 elite male and female soccer players to determine the prevalence of hip abnormalities. Athletes with a history of hip or groin injuries were included. Multiple radiographic parameters were used to assess the presence of cam and pincer-type femoroacetabular impingement. Measurements were conducted by a blinded, sports medicine fellowship–trained orthopaedic surgeon with experience in treating hip disorders. Results: In total, 72% (54/75) of male and 50% (10/20) of female players demonstrated some evidence of radiographic hip abnormality. Cam lesions were present in 68% (51/75) of men (76.5% [39/51] bilateral involvement) and 50% (10/20) of women (90% [9/10] bilateral involvement). Pincer lesions were present in 26.7% (20/75) of men and 10% (2/20) of women. The average male alpha angle overall was 65.6°. Cam-positive hips averaged 70.7°. The average female alpha angle overall was 52.9°, with cam-positive hips averaging 60.8°. Conclusion: The prevalence of radiographic hip abnormalities in elite soccer athletes is considerable, particularly in young male athletes. The establishment of the prevalence of these findings represents the first step in identifying the relationship between radiographic abnormalities and injuries of the hip and groin in athletes.
Predictors and Outcomes of Pneumonia in Patients With Spontaneous Intracerebral Hemorrhage
Authors: Alsumrain Mohammad , Melillo Nicholas , DeBari Vincent A. , Kirmani Jawad , Moussavi Mohammad , Doraiswamy Vikram , Katapally Ram , Korya Daniel , Adelman Marc , Miller Richard 
Published: February 2012

Objectives. Pneumonia is an important complication of spontaneous intracerebral hemorrhage (sICH). The purpose of this study was to determine the predictors and outcomes of the development of pneumonia in patients with sICH. Methods. In total, 290 consecutive patients with sICH admitted within 24 hours of stroke onset were investigated in a single center, retrospective study from January 2006 to July 2009. Clinical, biochemical, and imaging variables were registered. Stroke severity and functional outcomes were evaluated with the Glasgow Coma Scale (GCS) and modified Rankin Scale (mRS). Baseline variables that predicted pneumonia were investigated and outcomes were assessed. Results. The association of our primary exposure variables, such as mechanical ventilation, tube feeding, dysphagia, and tracheostomy, with pneumonia was highly significant ( P < .0001, for each variable). For mechanical ventilation, we observed an odds ratio (OR; 95% confidence interval [CI]) of 9.42 (4.24-20.9); for tube feeding, OR = 22.3 (8.91-55.8); for dysphagia, OR = 13.1 (4.66-36.7); and for tracheostomy, OR = 26.8 (8.02-89.3). After adjustment of potential confounders including GCS and mRS on admission, the use of angiotensin-converting enzyme inhibitors, proton pump inhibitors, and H2 blockers, all the adjusted OR (ORa) remained significant. For mechanical ventilation, the minimum ORa was 3.72 (95% CI: 1.68-8.26) when adjusted for GCS. For both dysphagia and tracheostomy, mRS reduced OR to 7.46 (95% CI: 3.34-10.6) in the case of dysphagia with an ORa of 16.2 (95% CI: 4.98 to 52.8) for tracheostomy. For tube feeding, both GCS and mRS reduced ORa; the former to 14.7 (95% CI: 6.16-35.0) and the latter to 15.7 (95% CI: 6.63-37.0). Pneumonia shows a significant effect on the morbidity ( P = .003), length of stay ( P < .0001), and mortality ( P = .041) rate of the patients. Conclusion. Mechanical ventilation, tube feeding, dysphagia, and tracheostomy are exposures associated with increased risk of the development of pneumonia in patients with sICH. Pneumonia is associated with an increase in morbidity, length of stay, and mortality among patients with sICH.
Familial Mediterranean fever-associated mutation pyrin E148Q as a potential risk factor for multiple sclerosis
Authors: Kümpfel T , Gerdes L-A , Wacker T , Blaschek A , Havla J , Krumbholz M , Pöllmann W , Feneberg W , Hohlfeld R , Lohse P 
Published: February 2012

Background: Familial Mediterranean fever (FMF) is an inherited autoinflammatory disease caused by mutations in the MEFV gene and characterized by recurrent febrile polyserositis. A possible association of FMF and multiple sclerosis (MS) has been suggested in cohorts from Turkey and Israel. Objective: The objective of this study was to investigate the prevalence of MEFV mutations in subjects with MS and in controls in Germany. Methods: One-hundred and fifty seven MS patients with at least one symptom or without symptoms suggestive of FMF from our outpatient clinic were investigated for mutations in exons 2, 3, and 10 of the MEFV gene (group 1). 260 independent MS patients (group 2) and 400 unrelated Caucasian controls (group 3) were screened selectively for the low-penetrance pyrin mutations E148Q and K695R Results: In group 1, 19 MS patients (12.1%) tested positive for a mutation in the MEFV gene, mainly the E148Q ( n=7) substitution. Fifteen of the 19 mutation-positive individuals reported at least one symptom suggestive of FMF. In three cases, we could identify additional family members with MS. In these pedigrees, the E148Q exchange co-segregated with MS ( p=0.026). Frequencies of the pyrin E148Q and K695R mutations were not statistically different between MS group 2 and controls but they occurred with a surprisingly high frequency in the German population. Conclusion: The MEFV gene appears to be another immunologically relevant gene locus which contributes to MS susceptibility. In particular, the pyrin E148Q mutation, which co-segregated with disease in three MS families, is a promising candidate risk factor for MS that should be further explored in larger studies.
Content and Complexity in Policy Reinvention and Diffusion: Gay and Transgender-Inclusive Laws against Discrimination
Authors: Taylor Jami K. , Lewis Daniel C. , Jacobsmeier Matthew L. , DiSarro Brian 
Published: February 2012

AbstractThis article sheds new light on policy diffusion by exploring policy complexity in state-level lesbian, gay, bisexual, and transgender (LGBT) antidiscrimination policies. The multiple component event history approach taken in this research allows for the concurrent study of both policy content and the factors that affect policy adoption. Results reveal that the factors influencing policy adoption vary depending on both the content and scope of the policy in question. In addition to addressing laws that protect gay people from discrimination, this article is one of the first studies in the political science and policy literature to empirically investigate the spread of transgender-inclusive laws. Despite combined advocacy and public conflation of identities, gay and transgender-inclusive laws appear to be influenced by different internal and external factors.