bluuebunny/crossref_metadata_2025_split huggingface dataset:
Value of non‐clinical cardiac repolarization assays in supporting the discovery and development of safer medicines
Authors: Valentin Jean‐Pierre , Pollard Chris , Lainée Pierre , Hammond Tim 
Published: January 2010

Non‐clinical QT‐related assays aligned to the pharmaceutical drug discovery and development phases are used in several ways. During the early discovery phases, assays are used for hazard identification and wherever possible for hazard elimination. The data generated enable us to: (i) establish structure–activity relationships and thereby; (ii) influence the medicinal chemistry design and provide tools for effective decision making; and provide structure–activity data for in silico predictive databases; (iii) solve problems earlier; (iv) provide reassurance for compound or project to progress; and (v) refine strategies as scientific and technical knowledge grows. For compounds progressing into pre‐clinical development, the ‘core battery’ QT‐related data enable an integrated risk assessment to: (i) fulfil regulatory requirements; (ii) assess the safety and risk–benefit for compound progression to man; (iii) contribute to defining the starting dose during the phase I clinical trials; (iv) influence the design of the phase I clinical trials; (v) identify clinically relevant safety biomarkers; and (vi) contribute to the patient risk management plan. Once a compound progresses into clinical development, QT‐related data can be applied in the context of risk management and risk mitigation. The data from ‘follow‐up’ studies can be used to: (i) support regulatory approval; (ii) investigate discrepancies that may have emerged within and/or between non‐clinical and clinical data; (iii) understand the mechanism of an undesirable pharmacodynamic effect; (iv) provide reassurance for progression into multiple dosing in humans and/or large‐scale clinical trials; and (v) assess drug–drug interactions. Based on emerging data, the integrated risk assessment is then reviewed in this article, and the benefit–risk for compound progression was re‐assessed. Project examples are provided to illustrate the impact of non‐clinical data to support compound progression throughout the drug discovery and development phases, and regulatory approval.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
Contact and photocontact sensitization in chronic actinic dermatitis: a changing picture
Authors: Chew Ai‐Lean , Bashir Saqib J , Hawk John LM , Palmer Roy , White Ian R , McFadden John P 
Published: January 2010

Background: Patients with chronic actinic dermatitis (CAD) frequently have positive patch or photopatch tests. In our previous study (period 1987–1992), the most prominent contact allergen was the sesquiterpene lactone mix (36% of patients with CAD). Objective: To assess whether contact allergy profiles in CAD patients between 2000 and 2005 have changed in respect to our previous data (1987–1992). Patients and Methods: Fifty CAD patient records from 2000 to 2005 for patch and photopatch testing were retrospectively analysed and data were compared with that from 86 patients seen between 1987 and 1992. Results: Thirty‐two (64%) and 64 (74%) patients had positive patch or photopatch tests in 2000–2005 and 1987–1992, respectively. The allergen profile has altered. A decline in sesquiterpene lactone mix positive reactions was noted: 29 (36%) patients were positive in 1987–1992 and 10 (20%) patients in 2000–2005, but this was not significant (P = 0.08). Reactions to non‐fragrance consumer allergens (i.e. p‐phenylenediamine and preservatives) had risen from 7 reactions (1987–1992) to 21 reactions in 13 individuals (2000–2005) (P < 0.001). Of these allergens, p‐phenylenediamine was the most common (12%; P = 0.004). Conclusions: A significant rise in positive patch tests to non‐fragrance consumer allergens, particularly p‐phenylenediamine, was seen in CAD patients in 2000–2005. We speculate this alteration of allergen profile may be partly due to changes in exposure patterns.
Epicutaneous patch testing in drug hypersensitivity syndrome (DRESS)
Authors: Santiago Felicidade , Gonçalo Margarida , Vieira Ricardo , Coelho Sónia , Figueiredo Américo 
Published: January 2010

Background: In some patterns of cutaneous adverse drug reactions, and depending on the culprit drug, patch testing has been helpful in confirming its cause. Its value in Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) has not been established in a large cohort of patients. Objective: The aim of the present study is to evaluate the safety and usefulness of patch testing in DRESS. Patients/Methods: Between January 1998 and December 2008, we studied 56 patients with DRESS induced by antiepileptic agents in 33 patients (59%), allopurinol in 19 (34%) and sulfasalazine, cotrimoxazole, tenoxicam, and amoxicillin in 1 patient each (7%). Results: A positive patch test reaction was observed in 18 patients (32.1%), of which 17 were with antiepileptics and 1 with tenoxicam. In the antiepileptic group, carbamazepine alone was responsible for 13 of 17 positive reactions (76.5%). Patch tests with allopurinol and its metabolite were negative in all cases attributed to this drug. Conclusions: In this study, patch testing was a safe and useful method in confirming the culprit drug in DRESS induced by antiepileptic drugs, whereas it had no value in DRESS induced by allopurinol. The pathogenesis of DRESS is not yet entirely clarified, but positive patch tests suggest a drug‐dependent delayed hypersensitivity mechanism.
Traumatic dental injuries in primary dentition: epidemiological study among preschool children in South Brazil
Authors: Wendt Flávia Prietsch , Torriani Dione Dias , Assunção Maria Cecília Formoso , Romano Ana Regina , Bonow Maria Laura Menezes , Da Costa Catiara Terra , Goettems Marília Leão , Hallal Pedro Curi 
Published: January 2010

AbstractAim:  To estimate the prevalence of traumatic injury in primary dentition among children aged 12–71 months old, as well as to evaluate the distribution of traumatic injuries, type of trauma and associated factors.Material and methods:  After the research project approval by the Ethics Research Committee, a cross‐sectional study was carried out including 571 preschool children – both from public and private schools – in the city of Pelotas, Southern Brazil. Data were collected by means of anterior teeth examination, and by the administration of a structured questionnaire to parents. The classification proposed by Andreasen & Andreasen was used, and crown discoloration and fistula were added to this criterion.Results and conclusions:  The prevalence of dental trauma was 36.6% (95% CI 32.7–40.5), with no significant differences between boys and girls. Trauma were more frequent among older children (P = 0.001). No associations were found for maternal schooling, income and type of school. The most frequent trauma was enamel fracture, and the most affected tooth was number 61. A significant statistical association was observed between the presence of dental trauma during clinical examination and parental report of trauma occurrence. The percentage of parents who looked for dental treatment was higher among children from private schools (P = 0.001). The most frequent place of occurrence was home, and the most frequently reported etiology was child’s own‐height fall.Conclusions:  Dental trauma in primary teeth is characterized as an accident that occurs due to the children’s development stage, even when they are cared for by mothers of higher schooling and income. Parents should search for assistance right after trauma occurrence to minimize sequelae.
Relationship of social cognitive theory concepts to mothers' dietary intake and BMI
Authors: Byrd‐Bredbenner Carol , Abbot Jaclyn Maurer , Cussler Ellen 
Published: January 2010

AbstractWomen tend to have the greatest responsibility for and influence on the home food environment. Understanding theoretical concepts as they pertain to mothers' food‐related behaviours could inform the development of interventions that enhance mothers' ability to create healthy family food environments that support optimal child development and help attenuate obesity rates. Likert scales assessed Social Cognitive Theory concepts [i.e. self‐efficacy, self‐regulation (sets goals, self‐reward, self‐monitoring, environmental structuring), outcome expectations] and coping of 201 mothers in the context food‐related activities. ANOVA determined whether diet and BMI differed among mothers scoring in the highest, middle, and lowest tertiles on the Likert scales. For self‐efficacy, coping, sets goals, and outcome expectations scales, lowest tertile mothers had significantly higher BMIs than highest tertile mothers. The lowest tertile for self‐efficacy, self‐reward, and self‐monitoring consumed significantly less fibre, vitamin C, magnesium, potassium, and fruit and vegetables than upper tertiles. On the self‐efficacy scale, the lowest tertile consumed significantly more calories, fat, and cholesterol than higher tertiles. Environmental structuring scale findings indicate users of television during dinner had significantly lower intakes of fibre, vitamin C, magnesium, potassium, and fruits and vegetables than those almost never using TV during dinner. Stepwise regression revealed self‐monitoring, environmental structuring, self‐reward, and outcome expectations were significant positive predictors of self‐efficacy. Self‐monitoring was a significant positive predictor of outcome expectations. Associations between theoretical concepts, mothers' dietary intakes, and BMIs point to the need to incorporate components that build self‐efficacy, self‐regulation, outcome expectations, and coping skills into health promotion interventions.
Control of Cell Number in the Bed Nucleus of the Stria Terminalis of Mice: Role of Testosterone Metabolites and Estrogen Receptor Subtypes
Authors: Hisasue Shin-ichi , Seney Marianne L. , Immerman Eleanor , Forger Nancy G. 
Published: January 2010

ABSTRACTIntroductionThe bed nucleus of the stria terminalis (BNST) exhibits several sex differences that may be related to male sexual behavior and gender identity. In mice and rats, sex differences in the principal nucleus of the BNST (BNSTp) are due to sexually dimorphic cell death during perinatal life. Although testosterone treatment of newborn female rats increases BNSTp cell number, the relevant hormone metabolite(s) are not known, and the effect of testosterone on the development of BNSTp cell number in mice has not been examined.AimTo identify the sex hormone metabolites and receptors controlling cell number, volume, and cell size in the BNSTp of mice.MethodsIn the first experiment, C57BL/6J male mice were injected on the day of birth with peanut oil; females were injected with testosterone propionate (TP), estradiol benzoate (EB), dihydrotestosterone propionate (DHTP), or oil alone, and the BNSTp of all animals was examined in adulthood. In the second experiment, to compare effects of EB to the effects of estrogen receptor subtype specific agonists, newborn female mice were injected with EB, propyl-pyrazole-triol (PPT, a selective estrogen receptor alpha [ERα] agonist), or diarylpropionitrile (DPN, a selective estrogen receptor beta [ERβ] agonist).Main Outcome MeasuresNuclear volume measurements and stereological cell counts in the BNSTp in adulthood.ResultsTP treatment of newborn females completely masculinized both BNSTp volume and cell number. EB masculinized neuron number, whereas DHTP had no effect on volume or cell number. In the second experiment, EB again fully masculinized neuron number in the BNSTp and in this study also masculinized BNSTp volume. PPT and DPN each significantly increased cell number, but neither completely mimicked the effects of EB.ConclusionsWe conclude that estrogenic metabolites of testosterone control sexually dimorphic cell survival in the BNSTp and that activation of both ERα and ERβ may be required for complete masculinization of this brain region.
Aging as a Related Factor of the Nursing Diagnosis Impaired Memory: Content Validation
Authors: Chaves Enaura Helena Brandão , De Barros Alba Lúcia Bottura Leite , Marini Maiko 
Published: January 2010

PURPOSE.  The purpose of this study was to conduct a content validation for the elements of the nursing diagnosis Impaired Memory and include aging as a related factor.METHOD.  Fehring's (1987) model of diagnosis content validation was used, with the participation of 18 experts.FINDING.  The definition, defining characteristics, and related factors of NANDA‐I were evaluated by experts, as was the proposed related factor “aging.”CONCLUSIONS.  Elements of the NANDA‐I diagnosis Impaired Memory and the proposed related factor of aging were validated in the Brazilian context. A clinical validation of this related factor will be necessary to build evidence for this relationship.IMPLICATIONS FOR NURSING PRACTICE.  NANDA‐I diagnoses should be tested and validated in the elderly, in order to take their specific needs into account, thus contributing to quality nursing care for these patients.OBJETIVO.  Realizar a validação de conteúdo dos elementos do diagnóstico de enfermagem Memória Prejudicada e incluir o envelhecimento como fator relacionado.MÉTODO.  Utilizou‐se o modelo de validação de conteúdo de diagnóstico de Fehring (1987) com a participação de 18 experts.RESULTADOS.  A definição, as características definidoras, os fatores relacionados da NANDA‐I foram validados pelos experts, assim como o proposto fator relacionado “envelhecimento”.CONCLUSÕES.  Os elementos do diagnóstico memória prejudicada da NANDA‐I e o proposto fator relacionado envelhecimento foram validados no contexto brasileiro. Faz‐se necessária a realização de validação clínica de fator relacionado para aumentar as evidências dessa relação.IMPLICAÇÕES PARA A PRÁTICA DE ENFERMAGEM.  Os diagnósticos da NANDA I devem ser testados e validados em idosos, para contemplar suas especificidades, e assim contribuir na qualidade da assistência de enfermagem a esses pacientes.
Estimation of 24‐Hour Sodium Excretion from Spot Urine Samples
Authors: Mann Samuel J. , Gerber Linda M. 
Published: January 2010

J Clin Hypertens (Greenwich). 2010;12:174–180. ©2010 Wiley Periodicals, Inc.Despite the effects of sodium intake on blood pressure and on response to antihypertensive medication, sodium intake is rarely monitored in clinical practice. The current method, the 24‐hour urine collection for sodium excretion, is cumbersome, often incorrectly performed, and not commonly ordered. Further, its results have limited meaning because of the substantial day‐to‐day variation in sodium intake. A spot urine test to enable convenient, inexpensive, and serial monitoring of sodium excretion would be desirable. In this study, the accuracy of predicting 24‐hour sodium excretion from a spot urine sample was assessed. The urine sodium/creatinine ratio was determined from the following urine samples: an “AM sample,” submitted at the beginning of the 24‐hour urine collection; a “PM sample” collected in the later afternoon/early evening before dinner, at roughly the midpoint of the collection; and a “random sample,” collected after its completion. The ratio was then corrected for 24‐hour creatinine excretion. The strongest correlation between predicted and actual 24‐hour sodium excretion was observed with the PM sample collected near the midpoint (r=0.86, P<.001). This sample also identified persons with sodium excretion <100 mEq/d with a sensitivity of 100% and specificity of 82%. The sodium/creatinine ratio from a spot urine sample collected in the late afternoon/early evening at roughly the midpoint of the 24‐hour collection, and adjusted for 24‐hour creatinine excretion, strongly correlated with 24‐hour sodium excretion. Additional studies are merited to further evaluate the role of the spot urine sample in assessing sodium intake.
Longitudinal Community‐Based Assessment of Blood Pressure Control Among Japanese Hypertensive Patients: Fukushima Research of Hypertension (FRESH)
Authors: Yokokawa Hirohide , Goto Aya , Sanada Hironobu , Watanabe Tsuyoshi , Yasumura Seiji 
Published: January 2010

J Clin Hypertens (Greenwich). 2010;12:166–173. ©2010 Wiley Periodicals, Inc.In this observational cohort study, the authors assessed the achievement of treatment goals as defined in the Japanese Society of Hypertension’s Guidelines for the Management of Hypertension (JSH 2004) among 2743 Japanese hypertensive patients who were followed for 1 year (follow‐up rate of 82.6%). Median age was 72 years, and 45% were men. Achievement of treatment goals across all 4 seasons was very low, at 4.1% among patients with diabetes mellitus or renal disease, 3.9% among nonelderly patients (<65 years of age) without these diseases, and 30.8% among elderly patients (≥65 years of age) without these diseases. These findings highlight the importance of maintaining appropriate blood pressure control. In addition, an analysis of factors associated with achievement rates identified the importance of weight control, lifestyle modification, and family history, and indicated a need for better blood pressure management before complications arise.
The Impact of Lactotripeptides on Blood Pressure Response in Stage 1 and Stage 2 Hypertensives
Authors: Germino F. Wilford , Neutel Joel , Nonaka Mako , Hendler Sheldon S. 
Published: January 2010

J Clin Hypertens (Greenwich). 2010;12:153–159. ©2010 Wiley Periodicals, Inc.Nearly 70 million Americans have hypertension, and approximately an equal number have prehypertension. The prevalence of both disorders increases with advancing age and obesity. Many at‐risk individuals do not have controlled blood pressure (BP). Lifestyle modification for most persons is the first step in a plan to control these conditions. Non–drug treatments offer an appeal to many patients with modest BP elevation. The authors recently evaluated BP response using 24‐hour ambulatory BP monitoring and office BP monitoring of lactotripeptides dosed twice daily in 91 previously treated and treatment‐naive patients with stage 1 and stage 2 hypertension. In this population, daytime systolic BP, the primary efficacy end point, significantly decreased (−3.6 mm Hg; P=.013), while placebo did not affect systolic BP (0 mm Hg; P=not significant). Treatment‐naive patients exhibited a more robust drop in their daytime systolic BP (−7.6 mm Hg; P=.005) compared with placebo (−3.6 mm Hg; P=not significant). Lactotripeptides may be an effective agent in the management of low‐risk and low‐grade hypertension and prehypertension.
Antihypertensive Medication Prescribing Patterns in a University Teaching Hospital
Authors: Axon R. Neal , Nietert Paul J. , Egan Brent M. 
Published: January 2010

J Clin Hypertens (Greenwich)Treatment of hypertension among hospitalized patients represents an opportunity to improve blood pressure recognition and treatment. To address this issue, the authors examined patterns of antihypertensive medication prescribing among 5668 hypertensive inpatients. Outcomes were treatment with any antihypertensive medication and treatment with first‐line therapy, defined as angiotensin‐converting enzyme inhibitors, β‐blockers, thiazide diuretics, or calcium channel blockers. Logistic regression models adjusting for age, sex, race, length of stay, service line, and comorbidity were used for all comparisons. The multivariate‐adjusted odds ratios for treatment were higher for men (1.4,P<.001), older patients (2.5 for age older than 80 vs 1.0 for age younger than 40;P<.001), non‐white race (1.2 vs 1.0 for white race;P<.004), and generalist service line (1.4 vs 1.0 for all other services;P<.001). Multivariate‐adjusted odds ratios for receiving first‐line agents were higher for older patients and generalist service line. Among surgical patients, receipt of medical consultation was only marginally associated with higher odds of antihypertensive or first‐line treatment after adjustment for relevant clinical variables. Demographic factors and service line appear to play a major role in determining the likelihood of inpatient hypertension treatment. Understanding and addressing these disparities has the potential to incrementally improve hypertension control rates in the population.
Coarse-grained transactions
Authors: Koskinen Eric , Parkinson Matthew , Herlihy Maurice 
Published: January 2010

Traditional transactional memory systems suffer from overly conservative conflict detection, yielding so-called false conflicts, because they are based on fine-grained, low-level read/write conflicts. In response, the recent trend has been toward integrating various abstract data-type libraries using ad-hoc methods of high-level conflict detection. These proposals have led to improved performance but a lack of a unified theory has led to confusion in the literature.
We clarify these recent proposals by defining a generalization of transactional memory in which a transaction consists of coarse-grained (abstract data-type) operations rather than simple memory read/write operations. We provide semantics for both pessimistic (e.g. transactional boosting) and optimistic (e.g. traditional TMs and recent alternatives) execution. We show that both are included in the standard atomic semantics, yet find that the choice imposes different requirements on the coarse-grained operations: pessimistic requires operations be left-movers, optimistic requires right-movers. Finally, we discuss how the semantics applies to numerous TM implementation details discussed widely in the literature.
Abstraction-guided synthesis of synchronization
Authors: Vechev Martin , Yahav Eran , Yorsh Greta 
Published: January 2010

We present a novel framework for automatic inference of efficient synchronization in concurrent programs, a task known to be difficult and error-prone when done manually.
Our framework is based on abstract interpretation and can infer synchronization for infinite state programs. Given a program, a specification, and an abstraction, we infer synchronization that avoids all (abstract) interleavings that may violate the specification, but permits as many valid interleavings as possible.
Combined with abstraction refinement, our framework can be viewed as a new approach for verification where both the program and the abstraction can be modified on-the-fly during the verification process. The ability to modify the program, and not only the abstraction, allows us to remove program interleavings not only when they are known to be invalid, but also when they cannot be verified using the given abstraction.
We implemented a prototype of our approach using numerical abstractions and applied it to verify several interesting programs.
Convergence Theorems for the Unique Common Fixed Point of a Pair of Asymptotically Nonexpansive Mappings in Generalized Convex Metric Space
Authors: Wang Chao , Li Jin , Zhu Daoli 
Published: January 2010

AbstractLet "Equation missing" be a generalized convex metric space, and let "Equation missing", "Equation missing" be a pair of asymptotically nonexpansive mappings. In this paper, we will consider an Ishikawa type iteration process with errors to approximate the unique common fixed point of "Equation missing" and "Equation missing".