bluuebunny/crossref_metadata_2025 huggingface dataset:
Total Serum Transforming Growth Factor‐β1 Is Elevated in the Entire Spectrum of Genetic Aortic Syndromes
Authors: Hillebrand Mathias , Millot Nathalie , Sheikhzadeh Sara , Rybczynski Meike , Gerth Sabine , Kölbel Tilo , Keyser Britta , Kutsche Kerstin , Robinson Peter N. , Berger Jürgen , Mir Thomas S. , Zeller Tanja , Blankenberg Stefan , von Kodolitsch Yskert , Goldmann Britta
Published: August 2014

Background

Total serum transforming growth factor‐beta 1 (tsTGF‐β1) is increased in patients with Marfan syndrome (MFS), but it has not been assessed in thoracic aortic aneurysm and dissection (TAAD), Loeys‐Dietz syndrome (LDS), and bicuspid aortic valve disease (BAVD).

Hypothesis

tsTGF‐β1 is increased in genetic aortic syndromes including TAAD, LDS, MFS, and BAVD.

Methods

We measured tsTGF‐β1 and performed sequencing of the genes FBN1, TGFBR1, and TGFBR2 in 317 consecutive patients with suspected or known genetic aortic syndrome (167 men, 150 women; mean age 43 ± 14 years). TAAD was diagnosed in 20, LDS in 20, MFS in 128, and BAVD in 30 patients, and genetic aortic syndrome was excluded in 119 patients.

Results

Elevated tsTGF‐β1 levels were associated with causative gene mutations (P = 0.008), genetic aortic syndrome (P = 0.009), and sporadic occurrence of genetic aortic syndrome (P = 0.048), whereas only genetic aortic syndrome qualified as an independent predictor of tsTGF‐β1 (P = 0.001). The tsTGF‐β1 levels were elevated in FBN1 and NOTCH1 mutations vs patients without mutations (both P = 0.004), and in NOTCH1 mutations vs ACTA2/MYH11 mutations (P = 0.015). Similarly, tsTGF‐β1 levels were elevated in MFS (P = 0.003) and in BAVD (P = 0.006) vs patients without genetic aortic syndrome. In contrast to specific clinical features of MFS, FBN1 in‐frame mutations (P = 0.019) were associated with increased tsTGF‐β1 levels.

Conclusions

tsTGF‐β1 is elevated in the entire spectrum of genetic aortic syndromes. However, gradual differences in the increases of tsTGF‐β1 levels may mirror different degrees of alteration of tsTGF‐β1 signaling in different genetic aortic syndromes.
US lung cancer trends by histologic type
Authors: Lewis Denise Riedel , Check David P. , Caporaso Neil E. , Travis William D. , Devesa Susan S.
Published: August 2014

BACKGROUND

Lung cancer incidence rates overall are declining in the United States. This study investigated the trends by histologic type and demographic characteristics.

METHODS

Surveillance, Epidemiology, and End Results (SEER) program rates of microscopically confirmed lung cancer overall and squamous cell, small cell, adenocarcinoma, large cell, other, and unspecified carcinomas among US whites and blacks diagnosed from 1977 to 2010 and white non‐Hispanics, Asian/Pacific Islanders, and white Hispanics diagnosed from 1992 to 2010 were analyzed by sex and age.

RESULTS

Squamous and small cell carcinoma rates declined since the 1990s, although less rapidly among females than males. Adenocarcinoma rates decreased among males and only through 2005, after which they then rose during 2006 to 2010 among every racial/ethnic/sex group; rates for unspecified type declined. Male/female rate ratios declined among whites and blacks more than among other groups. Recent rates among young females were higher than among males for adenocarcinoma among all racial/ethnic groups and for other specified carcinomas among whites.

CONCLUSIONS

US lung cancer trends vary by sex, histologic type, racial/ethnic group, and age, reflecting historical cigarette smoking rates, duration, cessation, cigarette composition, and exposure to other carcinogens. Substantial excesses among males have diminished and higher rates of adenocarcinoma among young females have emerged as rates among males declined more rapidly. The recognition of EGFR mutation and ALK rearrangements that occur primarily in adenocarcinomas are the primary basis for the molecular revolution that has transformed lung cancer diagnosis and treatment over the past decade, and these changes have affected recent type‐specific trends. Cancer 2014;120:2883–2892. © 2014 American Cancer Society.
Full‐Order observer design for nonlinear complex large‐scale systems with unknown time‐varying delayed interactions
Authors: Phat Vu N. , Thanh Nguyen T. , Trinh Hieu
Published: August 2014

This article is concerned with the problem of state observer for complex large‐scale systems with unknown time‐varying delayed interactions. The class of large‐scale interconnected systems under consideration is subjected to interval time‐varying delays and nonlinear perturbations. By introducing a set of argumented Lyapunov–Krasovskii functionals and using a new bounding estimation technique, novel delay‐dependent conditions for existence of state observers with guaranteed exponential stability are derived in terms of linear matrix inequalities (LMIs). In our design approach, the set of full‐order Luenberger‐type state observers are systematically derived via the use of an efficient LMI‐based algorithm. Numerical examples are given to illustrate the effectiveness of the result. © 2014 Wiley Periodicals, Inc. Complexity 21: 123–133, 2015
Triphenylamine‐Substituted Metalloporphyrins for Solution‐Processed Bulk Heterojunction Solar Cells: The Effect of the Central Metal Ion on Device Performance
Authors: Zhang Yunan , Zhang Shitong , Yao Liang , Qin Leiqiang , Nian Li , Xie Zengqi , Yang Bing , Liu Linlin , Ma Yuguang
Published: August 2014

A series of metal(II)‐substituted 5,10,15,20‐tetrakis[4‐(diphenylamino)phenyl]porphyrins (P) were designed and synthesized. Incorporation of the flexible and strong electron‐donating triphenylamine substituent endowed the porphyrins with enhanced solubility and intermolecular interactions. The distinct properties arising from different central metal ions were investigated by studying the absorption spectra, electrochemistry behavior, charge transport properties, thermal stability, and morphology characterization of the porphyrins. The PdII 5,10,15,20‐tetra(4‐diphenylaminophenyl)porphyrins (PPd) were found to have more matching energy levels with methyl [6,6]‐phenyl‐C‐61‐butyrate (PC61BM), higher hole mobility and longer triplet exciton lifetime. Bulk heterojunction solar cells based on porphyrins and PC61BM have been fabricated, with PPd‐based solar cells exhibiting greatly enhanced photovoltaic performance originating from a combination of elements. These results will help guide the future molecular design of porphyrins for application in organic small molecule bulk heterojunction solar cells.
Facile One‐Pot Transformation of Phenols into o‐Cyanophenols
Authors: Nakai Yuhta , Moriyama Katsuhiko , Togo Hideo
Published: August 2014

The treatment of phenols with paraformaldehyde in the presence of MgCl2 and Et3N in THF at 80 °C, followed by reaction with molecular iodine and aq. ammonia at room temperature provided the corresponding o‐cyanophenols in moderate to good yields. The present reaction is a one‐pot transformation of phenols into o‐cyanophenols using much less expensive reagents than are typically used; the reaction is free of both transition‐metals and cyanide. The utility of this reaction was highlighted during our preparation of Febuxostat from p‐bromophenol.
Maternal mood and concordant maternal and infant salivary cortisol during heel lance while in kangaroo care
Authors: Castral T.C. , Warnock F. , dos Santos C.B. , Daré M.F. , Moreira A.C. , Antonini S.R.R. , Scochi C.G.S.
Published: August 2014

Background

Maternal kangaroo care (MKC) is a naturalistic intervention that alleviates neonatal pain, and mothers are assumed to play a stress regulatory role in MKC. Yet, no MKC infant pain study has examined relationship between maternal and infant stress reactivity concurrently, or whether post‐partum depression and/or anxiety (PPDA) alters maternal and neonatal stress response and the regulatory effects of MKC.

Objectives

To examine the concordance of salivary cortisol reactivity between 42 mothers and their stable preterm infants during routine infant heel lance (HL) while in MKC and to compare salivary cortisol between groups of mothers with and without PPDA and their infants.

Methods

Maternal and infant salivary cortisol samples were collected pre‐HL and 20 min post‐HL with two additional maternal samples at night and in the morning. Mothers and infants were allocated to with PPDA versus without PPDA study groups on the basis of maternal post‐natal mental health assessment scores.

Results

Higher mothers' cortisol pre‐HL was weakly associated with higher infants' salivary cortisol in response to the HL procedure. Maternal depression and/or anxiety were not associated with infants' cortisol. During HL, both groups of mothers and infants showed no change in salivary cortisol.

Conclusions

Concordance between mother and infant salivary cortisol supports the maternal stress regulatory role in MKC. MKC may have stress regulatory benefits for mothers and their preterm infants during HL independent of PPDA. Future MKC studies that target mothers with altered mood will help to build on these findings.
Combined effects of the cyanobacterial toxin microcystin-LR and environmental factors on life-history traits of indigenous cladoceran Moina macrocopa
Authors: Kim Jungkon , Seo Jung-Kwan , Yoon Hyojung , Kim Pil-Je , Choi Kyunghee
Published: August 2014

Environmental factors are important in that they might interact with toxicants and could affect the concentration–response relationship of the toxicants in the water environment. Microcystins (MCs) produced by algal blooming are natural toxins that exert severe impacts on aquatic organisms. Despite the possibility of interaction effects between environmental factors and MCs, very few studies have been carried out to date. In the present study, the authors evaluated the effect of 3 environmental factors on chronic toxicity of MC-leucine-arginine (MC-LR; 0 µg/L, 0.8 µg/L, 4 µg/L, 20 µg/L, 100 µg/L, 500 µg/L) to the freshwater invertebrate Moina macrocopa. Three environmental factors were determined to reflect the reasonable worst conditions of the water body in South Korea: high water temperature (25 °C), the highest concentration of nutrients (ammonia-nitrogen [NH3-N] = 3.8 mg/L; nitrate-nitrogen [NO3-N] = 8.5 mg/L) during the occurrence of algal bloom, and 2 pH conditions of 7.0 and 9.0, which satisfy the test acceptance criteria for the Daphnia test. Among the various environmental factors being tested, high water temperature and NO3-N elevated chronic toxicity of MC-LR, whereas NH3-N reduced toxicity. Water pH did not influence chronic toxicity of MC-LR to M. macrocopa. This observation suggests that those environmental factors are responsible for changing the trend of MC-LR toxicity. Environ Toxicol Chem 2014;33:2560–2565. © 2014 SETAC
Local and Global Ancestry Inference and Applications to Genetic Association Analysis for Admixed Populations
Authors: Thornton Timothy A. , Bermejo Justo Lorenzo
Published: August 2014

Genetic association studies in recently admixed populations offer exciting opportunities to identify novel variants underlying phenotypic diversity. At the same time, genetic heterogeneity resulting from population admixture has to be accounted for to ensure validity of association tests. The whole‐genome sequence data and the genome‐wide single‐nucleotide polymorphism chip data for Mexican American individuals provided by Genetic Analysis Workshop 18 (GAW18) presents a unique opportunity to evaluate and compare methods for the statistical analysis of admixed genetic data. We summarize here the five contributions from the GAW18 working group on admixture mapping and adjusting for admixture. Although group members considered a variety of research topics, the general theme was inference and consideration of ancestry admixture in genetic analyses. The topics considered can be grouped into three categories: (1) global and local ancestry inference and estimation, (2) association and admixture mapping, and (3) genotype imputation in admixed samples. We describe the approaches that were used and the most relevant findings from each contribution. We also provide insight into the strengths and limitations of the state‐of‐the‐art methods considered for genetic analyses in admixed populations.
Testing Genetic Association With Rare and Common Variants in Family Data
Authors: Chen Han , Malzahn Dörthe , Balliu Brunilda , Li Cong , Bailey Julia N.
Published: August 2014

With the advance of next‐generation sequencing technologies in recent years, rare genetic variant data have now become available for genetic epidemiology studies. For family samples, however, only a few statistical methods for association analysis of rare genetic variants have been developed. Rare variant approaches are of great interest, particularly for family data, because samples enriched for trait‐relevant variants can be ascertained and rare variants are putatively enriched through segregation. To facilitate the evaluation of existing and new rare variant testing approaches for analyzing family data, Genetic Analysis Workshop 18 (GAW18) provided genotype and next‐generation sequencing data and longitudinal blood pressure traits from extended pedigrees of Mexican American families from the San Antonio Family Study. Our GAW18 group members analyzed real and simulated phenotype data from GAW18 by using generalized linear mixed‐effects models or principal components to adjust for familial correlation or by testing binary traits using a correction factor for familial effects. With one exception, approaches dealt with the extended pedigrees in their original state using information based on the kinship matrix or alternative genetic similarity measures. For simulated data our group demonstrated that the family‐based kernel machine score test is superior in power to family‐based single‐marker or burden tests, except in a few specific scenarios. For real data three contributions identified significant associations. They substantially reduced the number of tests before performing the association analysis. We conclude from our real data analyses that further development of strategies for targeted testing or more focused screening of genetic variants is strongly desirable.
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

Machine 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

Whole‐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

African 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

Diagnosis‐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

Objective

Antidepressants 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.

Design

The relevant literature is reviewed through a MEDLINE search via PubMed, focusing on agomelatine and clinical and preclinical research on ADS.

Results

Altered 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.

Conclusions

This 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

The 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

Despite 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

Increased 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.
Monitoring oxygen levels in orthotopic human glioma xenograft following carbogen inhalation and chemotherapy by implantable resonator‐based oximetry
Authors: Hou Huagang , Krishnamurthy Nemani Venkata , Du Gaixin , Montano Ryan , Song Rui , Gimi Barjor , Swartz Harold M. , Eastman Alan , Khan Nadeem
Published: August 2014

Hypoxia is a critical hallmark of glioma, and significantly compromises treatment efficacy. Unfortunately, techniques for monitoring glioma pO2 to facilitate translational research are lacking. Furthermore, poor prognosis of patients with malignant glioma, in particular glioblastoma multiforme, warrant effective strategies that can inhibit hypoxia and improve treatment outcome. EPR oximetry using implantable resonators was implemented for monitoring pO2 in normal cerebral tissue and U251 glioma in mice. Breathing carbogen (95% O2 + 5% CO2) was tested for hyperoxia in the normal brain and glioma xenografts. A new strategy to inhibit glioma growth by rationally combining gemcitabine and MK‐8776, a cell cycle checkpoint inhibitor, was also investigated. The mean pO2 of left and right hemisphere were ∼56–69 mmHg in the normal cerebral tissue of mice. The mean baseline pO2 of U251 glioma on the first and fifth day of measurement was 21.9 ± 3.7 and 14.1 ± 2.4 mmHg, respectively. The mean brain pO2 including glioma increased by at least 100% on carbogen inhalation, although the response varied between the animals over days. Treatment with gemcitabine + MK‐8776 significantly increased pO2 and inhibited glioma growth assessed by MRI. In conclusion, EPR oximetry with implantable resonators can be used to monitor the efficacy of carbogen inhalation and chemotherapy on orthotopic glioma in mice. The increase in glioma pO2 of mice breathing carbogen can be used to improve treatment outcome. The treatment with gemcitabine + MK‐8776 is a promising strategy that warrants further investigation.
From Side Chains Rattling on Picoseconds to Ensemble Simulations of Protein Folding
Authors: Larsson Per , Pouya Iman , Lindahl Erik
Published: August 2014

Simulations 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

Prolonged 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

College 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

Weights 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

Scores 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

Measures 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

Experimental 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.
DEVELOPMENT OF PERSONALITY TESTS FOR NAVAL OFFICER SELECTION II. VALIDATION OF EXPERIMENTAL TESTS AT U. S. NAVAL ACADEMY
Authors: Ricciuti Henry N. , French John W.
Published: August 2014

The objective of this research, which was conducted with the cooperation of the U. S. Naval Academy, was the development of personality measures to supplement the more scholastically oriented aptitude tests used in the selection of Naval Officers. Approximately the first year of the research was devoted to an analysis of the ratings of aptitude‐for‐service, or leadership potential, used at the Naval Academy. The second phase of the research, which is described in the present report, involved the development and validation of several personality tests intended to predict midshipmen aptitude‐for‐service ratings.

On the basis of findings obtained in the first phase of the research, five experimental personality tests were developed and administered in September 1951 to 462 midshipmen of the class of 1953. Three of these tests were objectively scorable: the Sense of Humor, Personality Trait, and Association Tests. Two of the tests, the Picture Interpretation and Story Completion Tests, were of the projective type.

Nine objective scores from the first three tests were intercorrelated with: a) aptitude‐for‐service ratings, b) class standings in conduct and in courses, and c) ability test scores. These personality test scores showed virtually no correlation with the aptitude‐for‐service ratings. An empirical key for the Personality Trait Test was developed on one‐half of the sample and cross‐validated on the other half, yielding a validity of .13. It is concluded that the objective tests included in the present analysis possess little or no validity for the prediction of aptitude ratings.

The Story Completion Test was analyzed by classifying the stories written by 118 midshipmen, representing upper and lower criterion groups, into categories which were assigned à priori scoring values. This à priori key yielded a small significant correlation (.25) with aptitude‐for‐service ratings. Using only the five best story stems resulted in a correlation of .22. An empirically modified key using only the best scoring categories for these five story‐stems yielded a significant validity of .19 when applied to the stories of another group of 116 midshipmen. Although these validities are not of immediate practical value, it is concluded that, with further refinements and research, including administration to pre‐admission groups, this type of test may hold considerable promise for the prediction of aptitude‐for‐service ratings.

It was not possible to analyze and validate the Picture Interpretation Test within the time and budgetary limitations of the present contract.
EFFECTS OF DIRECTIONS REGARDING GUESSING ON ITEM STATISTICS OF A MULTIPLE‐CHOICE VOCABULARY TEST
Authors: Swineford Frances , Miller Peter M.
Published: August 2014

A 100‐item vocabulary test containing 80 words of normal difficulty, ten extremely difficult words, and ten nonexistent “words” was administered to a group of 801 Annapolis first‐year students. There were three sets of directions, one third of the population being told nothing about guessing, one third being warned against guessing, and one third being encouraged to guess.

Directions not to guess were found to have the most direct effect on the number of questions attempted; students who were told nothing about guessing acted very similarly to students who were encouraged to guess. The tendency to guess proved to have an almost negligible positive relation to ability in the area of the test. The reliability of the test was lowered by the presence of the special items. Individual item difficulties were affected by the directions, deltas being higher where there was least guessing. Biserial correlations of the ordinary items were adversely affected, but to a slight extent only, by the presence of the special items. The very difficult items were found to react in exactly the same way as the nonsense items.
THE PREDICTED AND OBSERVED EFFECT OF CHANCE ON MULTIPLE‐CHOICE TEST VALIDITY*
Authors: Plumlee Lynnette B.
Published: August 2014

Assuming chance to be fully operative, the predicted effect of chance success on test validity when answer options are supplied depends on the number of options, the difficulty of the test and the variance of test scores. Predicted validity values are compared with empirical validity values in an experiment which used the same mathematics test items with and without answer options.
SPECTRAL ANALYSIS AND THE STUDY OF INDIVIDUAL DIFFERENCES IN THE PERFORMANCE OF ROUTINE, REPETITIVE TASKS
Authors: Abelson Robert P.
Published: August 2014

For the purpose of studying individual differences in the performance of routine, repetitive tasks, mathematical methods of analysis of data which is ordered along the time dimension are considered. Spectral analysis is chosen as the best method, since it gives a complete summarization of the stationary properties of time‐ordered data, and the measures derived from it possess convenient and orderly statistical properties. Spectral analysis decomposes the total oscillation of a time‐series into oscillations of varying rates, specifying the relative contribution of each of the components of oscillation.

Spectral analysis as an analytical tool is applied to available psychological data; in one case, to a study of “mental blocking,” and in another, to a study of serial patterns of response in an auditory discrimination. In both cases, spectral analysis leads to a modification and clarification that had been reached by the previous authors. Spectral analysis is then applied to the experimental data of the present paper.

The experimental task was that of jabbing a stylus repeatedly at a target line or lines. The deviations of the jabs from a reference line were measured in serial order, and the series were then subjected to a spectral analysis. Thirty‐three subjects were tested on five variations of the main task. Fifteen of the subjects were retested a month later. Task variations proved unimportant, but reliable individual differences were found in three measures, two of which did not depend on spectral analysis and one of which did.

These three measures were related to general personality characteristics by means of an inductive process. An individual who had had considerable contact with the experimental subjects in interview situations over a period of two years was asked to suggest personality factors which might have produced the differences found on each of the three measures. Without knowledge of the nature of the experimental measures, he suggested personality factors corresponding to them. These personality factors and their relation to routine, repetitive tasks are discussed.
ANALYSIS OF THE RELATIVE MOVEMENT TEST BY A METHOD OF INDIVIDUAL INTERVIEWS
Authors: Lucas Charles M.
Published: August 2014

The purpose of this study was to analyze performance on the Relative Movement Test, a part of the U. S. Navy Officer Classification Battery, in order to obtain a better understanding of what the test measures. More adequate information about the test should be of value in indicating how more effective measures may be produced for use by the Navy in selection and classification of personnel.

A preliminary analysis of answer sheets for the Relative Movement Test revealed that under normal administration conditions the test is speeded. The proportion of items not reached was considerably greater for the Relative Movement Test than for the other tests in the battery.

The analysis to be described here was based on data obtained from individual interviews. A sample of officer candidates, who had previously taken the test, were asked individually to do the problems aloud in an interview situation. Each subject described how he solved each of the group of selected items presented to him. All interviews were tape‐recorded.

At a later date, six judges listened to the recordings for the first 20 items of the test, and each judge wrote a description of the mental process he thought was involved in each solution. These descriptions were then sorted into categories according to type of mental process described and also according to item number.

The findings were as follows:

The test seems to provide a measure of spatial and deductive ability. The element of speededness in the regular examination procedure very likely provides a modifying condition, however.

Three groups of items were identified: (1) those judged to be primarily spatial, (2) those judged to be primarily deductive, and (3) those judged to be both spatial and deductive to an approximately equal extent.

Items judged as primarily spatial were generally the ones that required course or bearing answers, whereas those judged as primarily deductive generally required relative speed answers.

There was almost universal agreement among judges that spatial and deductive processes were involved in all but few of the reports. Judges differed among themselves with respect to the predominance of spatial and deductive processes.

No subject showed a tendency to employ any one of the above‐mentioned processes consistently from item to item. Processes were found to vary more as a function of the item than as a function of the subject.

It was recommended that studies should be performed in order to discover the relative validities of spatial items, deductive items, and items which involve both spatial and deductive ability, both under speeded and unspeeded conditions. Such studies would provide the final evidence regarding how best to use Relative Movement Test items in selection and classification of Naval personnel.