bluuebunny/crossref_metadata_2025_split huggingface dataset:
Applications of Machine Learning and Data Mining Methods to Detect Associations of Rare and Common Variants with Complex Traits
Authors: Lu Ake Tzu‐Hui , Austin Erin , Bonner Ashley , Huang Hsin‐Hsiung , Cantor Rita M. 
Published: August 2014

ABSTRACTMachine learning methods (MLMs), designed to develop models using high‐dimensional predictors, have been used to analyze genome‐wide genetic and genomic data to predict risks for complex traits. We summarize the results from six contributions to our Genetic Analysis Workshop 18 working group; these investigators applied MLMs and data mining to analyses of rare and common genetic variants measured in pedigrees. To develop risk profiles, group members analyzed blood pressure traits along with single‐nucleotide polymorphisms and rare variant genotypes derived from sequence and imputation analyses in large Mexican American pedigrees. Supervised MLMs included penalized regression with varying penalties, support vector machines, and permanental classification. Unsupervised MLMs included sparse principal components analysis and sparse graphical models. Entropy‐based components analyses were also used to mine these data. None of the investigators fully capitalized on the genetic information provided by the complete pedigrees. Their approaches either corrected for the nonindependence of the individuals within the pedigrees or analyzed only those who were independent. Some methods allowed for covariate adjustment, whereas others did not. We evaluated these methods using a variety of metrics. Four contributors conducted primary analyses on the real data, and the other two research groups used the simulated data with and without knowledge of the underlying simulation model. One group used the answers to the simulated data to assess power and type I errors. Although the MLMs applied were substantially different, each research group concluded that MLMs have advantages over standard statistical approaches with these high‐dimensional data.
Challenges of Linkage Analysis in the Era of Whole‐Genome Sequencing
Authors: Santorico Stephanie A. , Edwards Karen L. 
Published: August 2014

ABSTRACTWhole‐genome sequencing (WGS) is becoming an affordable technology for the study of the genetics of complex traits. With any new technology, experimental designs and statistical methods, both old and new, must be evaluated. One design seeing a resurgence of interest is the use of families. Genetic Analysis Workshop 18 provided the opportunity to evaluate statistical methods applied to WGS data for family‐based studies. We summarize the results of five contributions that used linkage in the context of WGS. The investigators took differing approaches, including assessment of false‐positive rates in classic two‐point linkage, the effects of heterogeneity on linkage and association tests, and the use of linkage to focus association tests. We describe the primary findings of each contribution and note challenges that are not new to those working in family designs or specific to WGS data; for example, choice of phenotype definition, covariate adjustment, and use of longitudinal data may produce different results, making comparisons challenging. We detail new issues brought about by WGS, such as the elevated genome‐wide false‐positive rate for classic two‐point parametric linkage analysis, computational demands in multipoint calculations, and lack of clarity in how to best use linkage to focus association testing. Finally, we comment on when linkage may be helpful for WGS, highlighting where additional research is needed; for example, although linkage analysis has been successful in the study of rare variants of large effect, how to best use family information in the context of rare variants of moderate effect remains an open research question.
Admixture Mapping Identifies a Quantitative Trait Locus Associated with FEV1/FVC in the COPDGene Study
Authors: Parker Margaret M. , Foreman Marilyn G. , Abel Haley J. , Mathias Rasika A. , Hetmanski Jacqueline B. , Crapo James D. , Silverman Edwin K. , Beaty Terri H. ,   the COPDGene Investigators
Published: August 2014

ABSTRACTAfrican Americans are admixed with genetic contributions from European and African ancestral populations. Admixture mapping leverages this information to map genes influencing differential disease risk across populations. We performed admixture and association mapping in 3,300 African American current or former smokers from the COPDGene Study. We analyzed estimated local ancestry and SNP genotype information to identify regions associated with FEV1/FVC, the ratio of forced expiratory volume in one second to forced vital capacity, measured by spirometry performed after bronchodilator administration. Global African ancestry inversely associated with FEV1/FVC (P = 0.035). Genome‐wide admixture analysis, controlling for age, gender, body mass index, current smoking status, pack‐years smoked, and four principal components summarizing the genetic background of African Americans in the COPDGene Study, identified a region on chromosome 12q14.1 associated with FEV1/FVC (P = 2.1 × 10−6) when regressed on local ancestry. Allelic association in this region of chromosome 12 identified an intronic variant in FAM19A2 (rs348644) as associated with FEV1/FVC (P = 1.76 × 10−6). By combining admixture and association mapping, a marker on chromosome 12q14.1 was identified as being associated with reduced FEV1/FVC ratio among African Americans in the COPDGene Study.
Introducing diagnosis‐related groups: is the information system ready?
Authors: Jian Weiyan , Lu Ming , Han Wei , Hu Mu 
Published: August 2014

SummaryDiagnosis‐related group (DRG) system is a classification system widely used in health managements, the foundation of which lies in the medical information system. A large effort had been made to improve the quality of discharge data before the introduction of DRGs in Beijing. We extract discharge data from 108 local hospitals spanning 4 years before and after standardization to evaluate the impact of standardization on DRG grouping performance. The data was grouped on an annual basis in accordance with Beijing's local DRG system. Proportion of ungrouped data, coefficient of variation (CV) and reduction in variance (RIV) were used to measure the performance of the DRG system. Both the descriptive and regression analysis indicate a significant reduction in terms of ungrouped data and CV for expenditure, increase of RIV for expenditure and length of stay. However, when there was no intervention, that is, between 2005 and 2006 and between 2008 and 2009, changes in these indicators were all insignificant. Therefore, the standardization of discharge data did improve data quality and consequently enhanced the performance of DRGs. Developing countries with a relatively weak information infrastructure should strengthen their medical information system before the introduction of the DRG system. Copyright © 2014 John Wiley & Sons, Ltd.
New insights on the antidepressant discontinuation syndrome
Authors: Harvey Brian H. , Slabbert Francois N. 
Published: August 2014

ObjectiveAntidepressants are at best 50–55% effective. Non‐compliance and the antidepressant discontinuation syndrome (ADS) are causally related yet poorly appreciated. While ADS is associated with most antidepressants, agomelatine seems to be devoid of such risk. We review the neurobiology and clinical consequences of antidepressant non‐compliance and the ADS. Agomelatine is presented as a counterpoint to learn more on how ADS risk is determined by pharmacokinetics and pharmacology.DesignThe relevant literature is reviewed through a MEDLINE search via PubMed, focusing on agomelatine and clinical and preclinical research on ADS.ResultsAltered serotonergic dysfunction appears central to ADS so that how an antidepressant targets serotonin will determine its relative risk for inducing ADS and thereby affect later treatment outcome. Low ADS risk with agomelatine versus other antidepressants can be ascribed to its unique pharmacokinetic characteristics as well as its distinctive actions on serotonin, including melatonergic, monoaminergic and glutamatergic‐nitrergic systems.ConclusionsThis review raises awareness of the long‐term negative aspects of non‐compliance and inappropriate antidepressant discontinuation, and suggests possible approaches to “design‐out” a risk for ADS. It reveals intuitive and rational ideas for antidepressant drug design, and provides new thoughts on antidepressant pharmacology, ADS risk and how these affect long‐term outcome. Copyright © 2014 John Wiley & Sons, Ltd.
Effects of forest roads on the hydrological response of a small‐scale mountain watershed in Greece
Authors: Soulis K. X. , Dercas N. , Papadaki CH. 
Published: August 2014

AbstractThe effects of land use changes on the ecology and hydrology of natural watersheds have long been debated. However, less attention has been given to the hydrological effects of forest roads. Although less studied, several researchers have claimed that streamflow changes related to forest roads can cause a persistent and pervasive effect on hillslope hydrology and the functioning of the channel system. The main potential direct effects of forest roads on natural watersheds hydrologic response are runoff production on roads surfaces due to reduced infiltration rates, interruption of subsurface flow by road cutslopes and rapid transfer of the produced runoff to the stream network through roadside ditches. The aforementioned effects may significantly modify the total volume and timing of the hillslope flow to the stream network. This study uses detailed field data, spatial data, hydro‐meteorological records, as well as numerical simulation to investigate the effects of forest roads on the hydrological response of a small‐scale mountain experimental watershed, which is situated in the east side of Penteli Mountain, Attica, Greece. The results of this study highlight the possible effects of forest roads on the watersheds hydrological response that may significantly influence direct runoff depths and peak flow rates. It is demonstrated that these effects can be very important in permeable watersheds and that more emphasis should be given on the impact of roads on the watersheds hydrological response. Copyright © 2014 John Wiley & Sons, Ltd.
Dynamic, discontinuous stream networks: hydrologically driven variations in active drainage density, flowing channels and stream order
Authors: Godsey S. E. , Kirchner J. W. 
Published: August 2014

AbstractDespite decades of research on the ecological consequences of stream network expansion, contraction and fragmentation, surprisingly little is known about the hydrological mechanisms that shape these processes. Here, we present field surveys of the active drainage networks of four California headwater streams (4–27 km2) spanning diverse topographic, geologic and climatic settings. We show that these stream networks dynamically expand, contract, disconnect and reconnect across all the sites we studied. Stream networks at all four sites contract and disconnect during seasonal flow recessions, with their total active network length, and thus their active drainage densities, decreasing by factors of two to three across the range of flows captured in our field surveys. The total flowing lengths of the active stream networks are approximate power‐law functions of unit discharge, with scaling exponents averaging 0.27 ± 0.04 (range: 0.18–0.40). The number of points where surface flow originates obey similar power‐law relationships, as do the lengths and origination points of flowing networks that are continuously connected to the outlet, with scaling exponents averaging 0.36–0.48. Even stream order shifts seasonally by up to two Strahler orders in our study catchments. Broadly, similar stream length scaling has been observed in catchments spanning widely varying geologic, topographic and climatic settings and spanning more than two orders of magnitude in size, suggesting that network extension/contraction is a general phenomenon that may have a general explanation. Points of emergence or disappearance of surface flow represent the balance between subsurface transmissivity in the hyporheic zone and the delivery of water from upstream. Thus the dynamics of stream network expansion and contraction, and connection and disconnection, may offer important clues to the spatial structure of the hyporheic zone, and to patterns and processes of runoff generation. Copyright © 2014 John Wiley & Sons, Ltd.
Identifying subsoil sediment sources with carbon and nitrogen stable isotope ratios
Authors: Laceby J. Patrick , Olley Jon , Pietsch Timothy J. , Sheldon Fran , Bunn Stuart E. 
Published: August 2014

AbstractIncreased sediment loads from accelerated catchment erosion significantly degrade waterways worldwide. In the South East Queensland region of Australia, sediment loads are degrading Moreton Bay, a Ramsar listed wetland of international significance. In this region, like most parts of coastal Australia, sediment is predominantly derived from gully and channel bank erosion processes. A novel approach is presented that uses carbon and nitrogen stable isotope ratios and elemental composition to discriminate between these often indistinguishable subsoil sediment sources. The conservativeness of these sediment properties is first tested by examining the effect of particle size separation (testing for consistency during transport) and the effect of sampling at different times (testing for temporal source consistency). The discrimination potential of these sediment properties is then assessed with the conservative properties, based on the particle size and temporal analyses, modelled to determine sediment provenance in three catchments. Nitrogen sediment properties were found to have significant particle size enrichment and high temporal variance indicative of non‐conservative behaviour. Conversely, carbon stable isotopes had very limited particle size and temporal variability highlighting their suitability for sediment tracing. Channel erosion was modelled to be a significant source of sediment (μ 51%, σ 9%) contrasting desktop modelling research that estimated gully erosion is the predominant sediment source. To limit the supply of sediment to Moreton Bay, channel bank and gully erosion must both be targeted by sediment management programs. By distinguishing between subsoil sediment sources, this approach has the potential to enhance the management of sediment loads degrading waterways worldwide. Copyright © 2014 John Wiley & Sons, Ltd.
From Side Chains Rattling on Picoseconds to Ensemble Simulations of Protein Folding
Authors: Larsson Per , Pouya Iman , Lindahl Erik 
Published: August 2014

AbstractSimulations of biological macromolecules have evolved tremendously since the discoveries of the 1970s. The field has moved from simple simulations in vacuo on picosecond scales to milliseconds of accurate sampling of large proteins, and it has become a standard tool in biochemistry and biophysics, rather than a dedicated theoretical one. This is partly due to increasing computational power, but it would not have been possible without huge research efforts invested in new algorithms and software. Here, we illustrate some of this development, both past and future challenges, and in particular, discuss how the recent introduction of modern ensemble methods is breaking the trend of ever‐longer simulations to instead focus on throughput and sampling. This has not only helped simulations become much more accurate, but it provides statistical error estimates, which are critical, as simulations are increasingly used to predict properties that have not yet been measured experimentally.
Endoplasmic reticulum stress and endothelial dysfunction
Authors: Lenna Stefania , Han Rong , Trojanowska Maria 
Published: August 2014

AbstractProlonged perturbation of the endoplasmic reticulum (ER) leads to ER stress and unfolded protein response (UPR) and contributes to the pathogenesis of various chronic disorders. This review focuses on the role of ER stress and UPR in endothelial cells and the relevance of these processes to vascular diseases. Chronic activation of ER stress and UPR pathways in endothelial cells leads to increased oxidative stress and inflammation and often results in cell death. Because endothelial cells play a pivotal role in maintaining vascular homeostasis, various pathological conditions interfering with this homeostasis including homocysteinemia, hyperlipidemia, high glucose, insulin resistance, disturbed blood flow, and oxidative stress can lead to endothelial dysfunction in part through the activation of ER stress. We discuss recently discovered aspects of the role of ER stress/UPR in those pathological conditions. We also summarize recent findings implicating ER stress and UPR in systemic hypertension as well as pulmonary arterial hypertension. Finally, this review will highlight a novel role of UPR mediators in the process of angiogenesis. © 2014 IUBMB Life, 66(8):530–537, 2014
AN ANALYSIS OF COURSE GRADES
Authors: French John W. 
Published: August 2014

ABSTRACTCollege grades suffer as a criterion for test development because of their unreliability and because of the difficulty of comparing the grades at one college with those at another. However, since they often constitute the best criterion we have, an optimum understanding of them is desirable. Toward this end, course grade criteria at two colleges were broken down into relatively homogeneous part‐grades. These were intercorrelated with the section scores of a special six‐hour aptitude test. In a number of cases final course grades are shown to be more heterogeneous than they should be to constitute a good criterion for test development, expecially where differential prediction is intended.The specific conclusions of this study are suggestive of the results that may be obtained from college course breakdowns of this type. They are of interest where specific course criteria, rather than scholastic averages are required. Some of the conclusions are: a) Unconventional parts of courses should be deleted from the course grade criterion. b) In English it is advisable to use a separate criterion for English, objective tests and English essays. c) Validation against part‐grades can reveal types of course material escaping present prediction.
A NOTE ON THE CALCULATION OF WEIGHTS FOR MAXIMUM BATTERY RELIABILITY
Authors: Green Bert F. 
Published: August 2014

ABSTRACTWeights may be determined for combining tests so that the composite has maximum reliability, but the calculation of these weights by means of the original equations is cumbersome. It is shown that the desired weighted composite is the first principal axis of a matrix closely related to the intercorrelation matrix. Thus simple and straightforward iterative procedures are available for calculating the weights.
VALIDITIES OF TESTS GIVEN IN JULY 1949 AND OF SUBTESTS OF THE POSTGRADUATE SCHOOL APTITUDE TEST FORM WNPF FOR PREDICTING AVERAGE GRADES FOR FIRST TWO TERMS AT THE U. S. NAVAL POSTGRADUATE SCHOOL
Authors: Mollenkopf William G. 
Published: August 2014

ABSTRACTScores on the seven aptitude and achievement tests given in July 1949 to members of the incoming class at the U. S. Naval Postgraduate School together with scores on the five parts of the Postgraduate School Aptitude Test Form WNPF have been related to the quality‐point ratios of the officers in this class for their first two terms at the Postgraduate School. Bar charts have been prepared which show for each of four score intervals on each test what per cent of students earned quality‐point ratios of 2.00 or higher. Product‐moment coefficients of correlation between scores on each test and the criterion of quality‐point ratios have also been computed.Consideration of the results of these two methods of evaluating the effectiveness of the tests reveals that the most promising tests are those in mechanics, mathematics, physics, experimental science, and engineering. Comparison with previously obtained results shows that consistent results have been found where similar tests were given in 1948 and 1949. Certain of the new tests tried out in 1949 were also found to be worthy of further investigation.It was concluded that the good progress made in the first year of research had been continued through the second year, and that by the end of the planned three‐year program of research it would be possible to indicate an effective test battery for use as part of the means of selecting Postgraduate School students.
TEST RELIABILITY AND EFFECTIVE TEST LENGTH
Authors: Angoff William H. 
Published: August 2014

ABSTRACTMeasures of effective test length are developed for speeded and power tests, which are independent of the number of items in the test or of the time required for administration. These measures are used in determining reliability for: 1) speeded and power tests, where a separately timed short parallel form is administered in addition to the full‐length test; 2) power tests, where a subset of items is imbedded within the total test, parallel to the total test; 3) power tests, where the subset of items is correlated with the complementary parallel subset in the test.
VALIDATION OF THE PRACTICAL JUDGMENT AND DIRECTED MEMORY EXPERIMENTAL SECTIONS OF ONE FORM OF THE LAW SCHOOL ADMISSION TEST
Authors: French John W. 
Published: August 2014

ABSTRACTExperimental half‐hour sections on Practical Judgment and Directed Memory were tried out with the Law School Admission Test in the spring of 1950. The validity of each of these sections was studied in terms of the improvement in prediction of first‐year grades at six law schools that would be affected by its addition to the regular test. Validities both with and without correction for restriction of range are considered. The Practical Judgment Test is of no value for prediction in this situation. The Directed Memory Test shows considerable promise in spite of overlap with the regular test.