bluuebunny/crossref_metadata_2025_split huggingface dataset:
Update on the evaluation of a new drug for effects on cardiac repolarization in humans: issues in early drug development
Authors: Salvi Vaibhav , Karnad Dilip R , Panicker Gopi Krishna , Kothari Snehal 
Published: September 2009

Following reports of death from cardiac arrhythmias with drugs like terfenadine and cisapride, the International Conference for Harmonization formulated a guidance (E14) document. This specifies that all new drugs must undergo a ‘thorough QT/QTc’ (TQT) study to detect drug‐induced QT prolongation, a surrogate marker of ventricular tachycardia, especially torsades de pointes (TdPs). With better understanding of data from several completed TQT studies, regulatory requirements have undergone some changes since the E14 guidance was implemented in October 2005. This article reviews the implications of the E14 guidance and the changes in its interpretation including choice of baseline QT, demonstration of assay sensitivity, statistical analysis of the effect of new drug and positive control, and PK‐PD modelling. Some issues like use of automated QT measurements remain unresolved. Pharmaceutical companies too are modifying Phase 1 studies to detect QTc liability early in order to save time and resources. After the E14 guidance, development of several drugs that prolong QTc by >5 ms is being abandoned by sponsors. However, all drugs that prolong the QT interval do not increase risk of TdP. Researchers in regulatory agencies, academia and industry are working to find better biomarkers of drug‐induced TdP which could prevent many useful drugs from being prematurely abandoned. Drug‐induced TdP is a rare occurrence. With fewer drugs that prolong QT interval reaching the licensing stage, knowing which of these drugs are torsadogenic is proving to be elusive. Thus, paradoxically, the effectiveness of the E14 guidance itself has made prospective validation of new biomarkers difficult.This article is part of a themed section on QT safety. To view this issue visit http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2010
Color Stability, Surface Roughness, and Surface Porosity of Acrylic Resins for Eye Sclera Polymerized by Different Heat Sources
Authors: Canadas Marília Daniela Busnardo , Garcia Lucas Fonseca Roberti , Consani Simonides , Pires‐de‐Souza Fernanda Carvalho Panzeri 
Published: September 2009

Abstract Purpose: The aim of this study was to evaluate the color stability, surface roughness, and surface porosity of acrylic resins for eye sclera polymerized by different heat sources and submitted to accelerated artificial aging (AAA). Materials and Methods: Three groups of ten specimens each were formed according to the heat source used during the polymerization cycle: GI—short cycle, GII—long cycle, and GIII—dry‐heat oven. The groups were submitted to color spectrophotometry through the CIE L*a*b* system and to surface roughness and porosity analysis using a Surfcorder IF 1700 profilometer. After the tests, specimens were submitted to AAA, with a maximum aging time of 384 hours, corresponding to a year of clinical use. After aging, the color and roughness of each group were assessed. Results: The results showed that the variability of ΔE was clinically unacceptable for all groups but the method of polymerization was insignificant (p > 0.05) for color change. For roughness, polymerization cycle was significant for the results. GIII (0.23 ± 0.06) presented the highest roughness difference (before and after AAA), statistically significant (p < 0.05) from GII. No statistically significant difference could be found among groups when considering the porosity test. Conclusion: It may be concluded that irrespective of the type of heat used for polymerization, there was an intense color alteration, to clinically unacceptable levels, when the specimens were submitted to AAA. For the other properties, alterations were less intense.
Day surgery visits for dental problems
Authors: Quiñonez Carlos , Gibson Debbie , Jokovic Aleksandra , Locker David 
Published: September 2009

Abstract –  Objectives:  To fill an information gap for dental care policy stakeholders in Canada, this pilot study explored the nature of day surgery (DS) visits for dental problems in Ontario, the country’s largest province.Methods:  The Canadian Institute for Health Information’s National Ambulatory Care Reporting System was used, which contains demographic, diagnostic, procedural and administrative information for ambulatory care settings across Ontario. Fiscal years 2003/2004 to 2005/2006 data were included for DS visits that had a main problem coded with an International Classification of Diseases code in the range K00‐K14, representing diseases of the oral cavity, salivary glands and jaws.Results:  During this period, approximately 75 791 persons made 79 133 DS visits for dental problems in Ontario. Proportionally, children under 5 years of age with dental caries represent the majority of DS visits. Restorations and extractions were the most frequently performed DS care procedure.Conclusions:  This is the first study of its kind in Canada, and confirms many of the assumptions held about DS care for dental problems. The study also acts as a baseline for ongoing quality improvement and planning within the province of Ontario.
Abnormal dose-response melatonin suppression by light in bipolar type I patients compared with healthy adult subjects
Authors: Hallam Karen T. , Begg Denovan P. , Olver James S. , Norman Trevor R. 
Published: September 2009

Objective:Among potential endophenotypes proposed for bipolar affective disorder focusing on circadian abnormalities associated with the illness has particularly high face validity. Melatonin sensitivity to light is one circadian endophenotype proposed as useful in bipolar disorder. The aim of this study was to investigate melatonin sensitivity to light over a range of light intensities in order to compare and contrast responses in bipolar I patients with those of healthy adult volunteers.Methods:The study included seven patients (4 females, 3 males) with bipolar I disorder and 34 control participants (22 females, 12 males) with no personal or family history of affective illness. Melatonin sensitivity to light was determined in all patients and participants across a range of light intensities (0, 200, 500 and 1000 lux).Results:The results indicated that patients showed melatonin super-sensitivity to light in comparison with controls, a response that was consistent across the entire light intensity range investigated.Conclusion:The study provides further evidence for a super sensitive response in bipolar I patients and suggests that its potential usefulness as an endophenotypic marker of the illness is deserving of further research.
Ownership Concentration and Product Innovation in Chinese Firms: The Mediating Role of Learning Orientation
Authors: Li Yuan , Guo Hai , Yi Yaqun , Liu Yi 
Published: September 2009

AbstractDrawing on institutional theory, this study empirically examines the relationship between a firm's levels of ownership concentration and product innovation and the mediating effect of learning orientation, using a sample of 351 Chinese firms. Does ownership concentration hinder or promote firm innovation? Perspectives on this relationship are divergent. This study examines the link between ownership concentration and product innovation and further examines whether and how ownership influences firm innovation through organizational learning. The results suggest that ownership concentration has an inverse U-shaped relationship to product innovation and to learning orientation. In addition, learning orientation mediates the curvilinear relationship between ownership concentration and product innovation. We discuss the study's contributions, managerial implications and directions for future research.
Structural and mutational analysis of TenA protein (HP1287) from the Helicobacter pylori thiamin salvage pathway – evidence of a different substrate specificity
Authors: Barison Nicola , Cendron Laura , Trento Alberto , Angelini Alessandro , Zanotti Giuseppe 
Published: September 2009

HP1287 (tenA) from Helicobacter pylori is included among the genes that play a relevant role in bacterium colonization and persistence. The gene has been cloned and its product, protein TenA, has been expressed and purified. The crystal structures of the wild‐type protein and the mutant F47Y have been determined at resolutions of 2.7 and 2.4 Å, respectively. The molecular model, a homotetramer with 222 symmetry, shows that the H. pylori TenA structure belongs to the thiaminase II class of proteins. These enzymes were recently found to be involved in a salvage pathway for the synthesis of the thiamin precursor hydroxypyrimidine, which constitutes a building block in thiamin biosynthesis, in particular in bacteria living in the soil. By contrast, enzymatic measurements on TenA from H. pylori indicate that the activity on the putative substrate 4‐amino‐5‐aminomethyl‐2‐methylpyrimidine is very modest. Moreover, in the present study, we demonstrate that the mutation at residue 47, a position where a phenylalanine occurs in all the strains of H. pylori sequenced to date, is not sufficient to explain the very low catalytic activity toward the expected substrate. As a result of differences in the colonization environment of H. pylori as well as the TenA structural and catalytic peculiar features, we suggest a possible pivotal role for the H. pylori enzyme in the thiamin biosynthetic route, which is in agreement with the relevance of this protein in the stomach colonization process.Structured digital abstract
MINT‐7260232: TenA (uniprotkb:O25874) and TenA (uniprotkb:O25874) bind (MI:0407) by x‐ray crystallography (MI:0114)
An engineered right‐handed coiled coil domain imparts extreme thermostability to the KcsA channel
Authors: Yuchi Zhiguang , Pau Victor P. T. , Lu Bridget X. , Junop Murray , Yang Daniel S. C. 
Published: September 2009

KcsA, a potassium channel from Streptomyces lividans, was the first ion channel to have its transmembrane domain structure determined by crystallography. Previously we have shown that its C‐terminal cytoplasmic domain is crucial for the thermostability and the expression of the channel. Expression was almost abolished in its absence, but could be rescued by the presence of an artificial left‐handed coiled coil tetramerization domain GCN4. In this study, we noticed that the handedness of GCN4 is not the same as the bundle crossing of KcsA. Therefore, a compatible right‐handed coiled coil structure was identified from the Protein Data Bank and used to replace the C‐terminal domain of KcsA. The hybrid channel exhibited a higher expression level than the wild‐type and is extremely thermostable. Surprisingly, this stable hybrid channel is equally active as the wild‐type channel in conducting potassium ions through a lipid bilayer at an acidic pH. We suggest that a similar engineering strategy could be applied to other ion channels for both functional and structural studies.Structured digital abstract
MINT‐7260032: kcsA (uniprotkb:P0A334) and kcsA (uniprotkb:P0A334) bind (MI:0407) by molecular sieving (MI:0071)
MINT‐7260022: kcsA (uniprotkb:P0A334) and kcsA (uniprotkb:P0A334) bind (MI:0407) by circular dichroism (MI:0016)
The Distribution of Japonica Rice Cultivars in the Lower Region of the Yangtze River Valley is Determined by Its Photoperiod‐sensitivity and Heading Date Genotypes
Authors: Wei Xiang‐Jin , Jiang Ling , Xu Jun‐Feng , Liu Xi , Liu Shi‐Jia , Zhai Hu‐Qu , Wan Jian‐Min 
Published: September 2009

Abstract There are generally four recognized classes of japonica rice cultivars grown in the lower region of the Yangtze River valley. The geographical distribution of the four classes is latitude‐dependent. Variation for heading date (HD) among 29 japonica rice cultivars grown in the lower region of the Yangtze River valley and belonging to the four classes was characterized, and their sensitivity to variations in photoperiod and temperature was analyzed. All of the cultivars were sensitive to both photoperiod and temperature. A regression analysis showed that HD is closely correlated with photoperiod sensitivity (PS). The PS of the four classes increased gradually from the medium maturing middle (MMM) types, through the late maturing middle (LMM) and early maturing late (EML) types to the medium maturing late (MML) types. Crosses with tester lines established that almost all of the cultivars carry the dominant early‐heading allele at Ef‐1, the photoperiod insensitive allele e2 and the PS alleles E1 or E1t. Most of the MMM, LMM and MML types carry the insensitive allele e3, while EML types have either E3 or E3t. At Se‐1, MMM and LMM types have Se‐1e, some EML types have Se‐1e and others Se‐1n, while the MML types are mostly Se‐1n. The PS of some MMM, LMM and EML types is reduced by the presence of hd2. These results show that the distribution of the four rice cultivar classes from high latitude to low latitude regions depended on a gradual increase in PS, which is mainly determined by its HD genotypes.
INFLUENCE OF WATER ACTIVITY, pH, HEAT TREATMENT AND PRESERVATIVE ON CHEMICAL CHANGES IN CANNED INDIAN COTTAGE CHEESE (PANEER) DURING STORAGE
Authors: RAO KULKARNI JAYARAJ , PATIL GIRIDHARI R. 
Published: September 2009

ABSTRACT Influence of water activity (Aw), pH and heat treatment on the chemical changes such as Maillard browning, oxidation and lipolysis in canned paneer has been studied by response surface methodology. Browning in canned paneer in terms of hydroxymethylfurfural content increased during storage; however, it was pH dependent. At pH above 5.0, the rate of browning decreased as Aw increased from 0.90 to 0.98. At pH below 5.0, the rate increased with increased Aw from 0.90 to 0.98. Maximum browning rates were observed at pH 5.2–5.6, low Aw values (0.90–0.92) and high heat treatment levels (up to F value 0.8). At all pH levels, increased Aw increased the oxidation rate, more so at low pH levels. Up to an F value of 0.3, heat treatment seemed to have aided the oxidation rate, but higher F values retarded the oxidation rate, more so at low Aw. Lipolysis occurred during storage, but pH had little effect on the rate of lipolysis. High Aw supported high lipolysis rates.PRACTICAL APPLICATIONSRaw paneer (Indian cottage cheese), popular with people in Indian subcontinent and with Indian diasporas scattered in several countries, has a shelf life of less than a day at ambient temperatures. Several attempts are being made by workers to improve the shelf life of paneer by canning process so that its market within the country and abroad improves. However, canning at usual canning time–temperatures is leading to intense chemical changes in paneer, which is not being accepted by consumers. Authors have tried to obviate such unacceptable chemical changes by reducing the intensity of canning process by adjusting so called “hurdles” of the product by hurdle technology. The present paper is a part of that attempt describing the chemical changes in paneer subjected to low heat intensity canning process with altered “hurdles.” Because the chemical changes occurring in a food product are a function of various parameters called “hurdles” like pH, water activity, heat treatment, etc., the present work attempted to identify the combination of the “hurdles” at which chemical changes are the slowest, which may find better acceptance with consumers.
EFFECT OF DIRECT APPLICATIONS OF SAGE (SALVIA OFFICINALIS L.) LEAVES ON OXIDATIVE STABILITY OF SUNFLOWER OIL DURING ACCELERATED STORAGE
Authors: ÇALIKOĞLU EDA , KIRALAN MUSTAFA , BAYRAK ALİ 
Published: September 2009

ABSTRACT In this study, various sage applications were examined on oxidative stability of sunflower oil during accelerated storage. There are three applications: (1) direct sage leaves (S); (2) deodorized sage leaves (DeS); and (3) essential oil of sage leaves. The main compounds of essential oil were identified asα‐thujone (35.87%),β‐thujone (14.41%), 1,8‐cineol (10.59%) and camphor (10.09%). Oxidative stability of these three applications was tested by Schall Oven test at 60C applying peroxide value and conjugated dienes, and Rancimat at 110C. Whereas the highest antioxidants activity was found for 2% S followed by 0.5% S and 2% DeS, all sage treatments statistically retarded the oxidation compared with the control sample. The most appealing result was that the residue can be used as a natural antioxidants. That means the reuse of residue may decrease economic losses and health risk in comparison with synthetic antioxidants and extracts because it is completely natural and contains no residual solvent.PRACTICAL APPLICATIONSWhile almost all of previous studies were concentrated on the use of herb extracts, our study investigates the results of direct application of sage on oxidation. Especially with this study, we have evaluated a possible application area for sage residue leftover after the deodorization process.
QUALITY CHANGES IN FRESH CHIVES (ALLIUM SCHOENOPRASUM L.) DURING REFRIGERATED STORAGE
Authors: VIÑA SONIA Z. , CERIMELE ELSA L. 
Published: September 2009

ABSTRACT This study investigates quality changes in fresh chives stored at 0 and 4C during 21 and 14 days, respectively. The product was packaged in trays and covered with polyvinyl chloride films. Weight loss, surface color, total chlorophyll, carotenoids, reducing sugars and browning potential were evaluated in order to determine shelf life at each temperature. In addition, internal atmosphere composition, total phenolics, radical scavenging activity and ascorbic acid content were measured for samples stored at 0C. Results showed that surface color change and losses of green pigments and reducing sugar content could be delayed for a week by storing fresh chives at 0C. The increase in browning potential was of lower magnitude at 0C than at 4C. High quality levels and marketability of fresh chives could be maintained for 2 weeks at 0C. PRACTICAL APPLICATIONSThe marketing of packaged and refrigerated, value‐added culinary herbs is a choice of increasing interest for vegetables processors. However, data on changes in the chemical composition and antioxidative properties of fresh herbs during storage are scarce. This study provides information on how quality attributes of fresh chives are affected under different conditions of postharvest handling and storage.
Buck‐Passing Accounts of Value
Authors: Suikkanen Jussi 
Published: September 2009

AbstractThis paper explores the so‐called buck‐passing accounts of value. These views attempt to use normative notions, such asreasonsandoughtto explain evaluative notions, such asgoodnessandvalue. Thus, according to Scanlon’s well‐known view, the property of being good is the formal, higher‐order property of having some more basic properties that provide reasons to have certain kind of valuing attitudes towards the objects. I begin by tracing some of the long history of such accounts. I then describe the arguments which are typically used to motivate these views. The rest of this article investigates how some of the central details of the buck‐passing accounts should be specified, and what kind of problems these views face.
Rurality and Other Determinants of Early Colorectal Cancer Diagnosis in Nebraska: A 6‐Year Cancer Registry Study, 1998‐2003
Authors: Sankaranarayanan Jayashri , Watanabe‐Galloway Shinobu , Sun Junfeng , Qiu Fang , Boilesen Eugene , Thorson Alan G. 
Published: September 2009

ABSTRACT:
Background:

There are no studies of rurality, and other determinants of colorectal cancer (CRC) stage at diagnosis with population‐based data from the Midwest. Methods: This retrospective study identified, incident CRC patients, aged 19 years and older, from 1998‐2003 Nebraska Cancer Registry (NCR) data. Using federal Office of Management and Budget classifications, we grouped patients by residence in metropolitan, micropolitan nonmetropolitan, or rural nonmetropolitan counties (non‐core based statistical areas). In univariate and multivariate logistic regression analyses, we examined the association of the county classification and of other determinants with early (in situ/local) versus late (regional/distant) stage at CRC diagnosis. Results: Of the 6,561 CRC patients identified, 45% were from metropolitan counties, 24% from micropolitan nonmetropolitan counties and 31% from rural nonmetropolitan counties, with 32%, 38%, and 33%, respectively, being diagnosed at an early stage. Multivariate analysis showed micropolitan nonmetropolitan residents were significantly more likely than rural nonmetropolitan residents to be diagnosed at an early stage (adjusted OR, 1.22; 95% CI: 1.05‐1.42, P < .05). However, rural nonmetropolitan and metropolitan residents did not significantly differ in the likelihood of early diagnosis. Residents with Medicare rather than those with private insurance (P < .0001), married rather than unmarried residents (P < .01), and residents with rectal cancer rather than those with colon cancer (P < .0001) were more likely to be diagnosed at an early stage. Conclusions: Early CRC diagnosis needs to be increased in rural (non‐core) non‐metropolitan residents, unmarried residents, and those with private insurance.
Does Distance Matter? Distance to Mammography Facilities and Stage at Diagnosis of Breast Cancer in Kentucky
Authors: Huang Bin , Dignan Mark , Han Daikwon , Johnson Owen 
Published: September 2009

ABSTRACT:
Background:

National and regional data indicate that breast cancer early detection is low in Kentucky, especially rural regions, perhaps because access to mammography services can be problematic. Objective: This study examined the distance between residences of women diagnosed with breast cancer and the nearest mammography facility, as a risk factor for advanced stage diagnosis in rural populations. Methods: 1999‐2003 Kentucky Cancer Registry data were used for this study. A total of 12,322 women, aged 40 and older at diagnosis, with no previous history of cancer, and with known cancer stage were included. Travel distance was obtained using a geographic information system (GIS). Hierarchical logistic regression models were used to analyze the relationship between travel distance and advanced stage diagnosis. Results: Advanced diagnoses had longer average travel distances than early stage diagnoses (P < 0.01). After adjusting for age, race, insurance, and education at census tract level, the odds of advanced diagnosis were significantly greater for women residing over 15 miles from a facility, compared to those living within 5 miles (adjusted OR = 1.50, 95% CI = 1.25‐1.80). Conclusion: Although socioeconomic status, race, and age may help explain advanced diagnoses, longer travel distance also adversely affects early detection for rural populations. Accurate measurement of spatial accessibility indicators, such as travel distance, facilitates identification of at‐risk groups so that interventions can be developed to reduce this disease.