bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structure Response and Clipping Factor Variabilities Using Probabilistic In-Structure Response Spectra for Functional Seismic Fragility Evaluation of Equipment
Authors: Samuelson-Sanford Cameron B. , Grant Frederic F. , Hashimoto Philip S. , Bayraktarli Yahya Y. 
Published: December 2015

For seismic probabilistic safety assessment of nuclear power plants (NPPs), test-based seismic fragilities for equipment can be developed using the results of dynamic testing. Electric Power Research Institute (EPRI) TR-103959 [1] formulates test-based equipment fragilities by comparing broadband test response spectra (TRS) to broadband demand spectra. Alternatively, broadband capacity spectra based on earthquake experience can be compared to broadband demand spectra to develop seismic fragilities for equipment that meet the screening criteria of EPRI NP-6041-SL [2].
In-structure demand spectra can exhibit narrow spectral peaks. A clipping factor recommended by EPRI TR-103959 [1] is typically used to clip these peaks to obtain median broadband demand spectra for comparison to broadband TRS. Similarly, a clipping factor recommended by EPRI NP-6041-SL [2] is typically used to obtain conservative deterministic broadband demand spectra for seismic margin assessment.
Four methods are investigated to assess their applicability for estimating clipping factor variability and structure response variability from probabilistic in-structure response spectra (ISRS) with narrow spectral peaks. Probabilistic ISRS at a given structural degree of freedom (DOF) are obtained from thirty simulations by the Latin Hypercube Sampling method. The most rigorous method involves independently clipping each of the thirty probabilistic ISRS. Structure response and clipping factor variabilities are calculated based on statistical analyses of the thirty clipped ISRS.
The other three methods are simplified alternatives to the more rigorous method and require less quantification effort. They involve calculating the median and 84th percentile non-exceedance probability (NEP) ISRS from the thirty unclipped ISRS. The clipping factors and associated clipping factor and structural response variabilities are calculated following the guidance of EPRI TR-103959 [1] and EPRI NP-6041-SL [2].
The results of the four methods are compared, and recommendations for determining the total variability due to structure response and peak clipping are developed. Two approaches that take the lesser combined variability for structure response and clipping from two methods are found to reasonably approximate the more rigorous method.
Performance-Based Design of Buried Steel Pipes at Fault Crossings
Authors: Akbas Bulent , O’Rourke Michael , Uckan Eren , Shen Jashue , Caglar Merve 
Published: December 2015

Buried steel pipes are commonly used in oil and gas industry for transmitting hydrocarbon products. Fault crossing is considered as one of the most important extreme events. Buried steel pipes are more vulnerable to compressive strains as compared to tensile strains. Therefore, the orientation angle of the pipe with respect to the fault should be arranged in such a way so as to promote net tension in the pipe.
In this study, a numerical study is carried out on a simplified numerical model to determine the seismic demand on steel pipes at fault crossings. The proposed model permits plastic hinge formation in the pipe due to incrementally applied fault movements, allow determining the critical length of the pipeline and measure strains developed on the tension and compression sides in the pipe. Based on the analyses carried out on the simple model and previous studies, two performance levels are defined for pipelines; namely, fully functional and partially functional.
Health economic burden that wounds impose on the National Health Service in the UK
Authors: Guest Julian F , Ayoub Nadia , McIlwraith Tracey , Uchegbu Ijeoma , Gerrish Alyson , Weidlich Diana , Vowden Kathryn , Vowden Peter 
Published: December 2015

ObjectiveTo estimate the prevalence of wounds managed by the UK's National Health Service (NHS) in 2012/2013 and the annual levels of healthcare resource use attributable to their management and corresponding costs.MethodsThis was a retrospective cohort analysis of the records of patients in The Health Improvement Network (THIN) Database. Records of 1000 adult patients who had a wound in 2012/2013 (cases) were randomly selected and matched with 1000 patients with no history of a wound (controls). Patients’ characteristics, wound-related health outcomes and all healthcare resource use were quantified and the total NHS cost of patient management was estimated at 2013/2014 prices.ResultsPatients’ mean age was 69.0 years and 45% were male. 76% of patients presented with a new wound in the study year and 61% of wounds healed during the study year. Nutritional deficiency (OR 0.53; p<0.001) and diabetes (OR 0.65; p<0.001) were independent risk factors for non-healing. There were an estimated 2.2 million wounds managed by the NHS in 2012/2013. Annual levels of resource use attributable to managing these wounds and associated comorbidities included 18.6 million practice nurse visits, 10.9 million community nurse visits, 7.7 million GP visits and 3.4 million hospital outpatient visits. The annual NHS cost of managing these wounds and associated comorbidities was £5.3 billion. This was reduced to between £5.1 and £4.5 billion after adjusting for comorbidities.ConclusionsReal world evidence highlights wound management is predominantly a nurse-led discipline. Approximately 30% of wounds lacked a differential diagnosis, indicative of practical difficulties experienced by non-specialist clinicians. Wounds impose a substantial health economic burden on the UK's NHS, comparable to that of managing obesity (£5.0 billion). Clinical and economic benefits could accrue from improved systems of care and an increased awareness of the impact that wounds impose on patients and the NHS.
Protocol of the adaptive study of IL-2 dose frequency on regulatory T cells in type 1 diabetes (DILfrequency): a mechanistic, non-randomised, repeat dose, open-label, response-adaptive study
Authors: Truman Lucy A , Pekalski Marcin L , Kareclas Paula , Evangelou Marina , Walker Neil M , Howlett James , Mander Adrian P , Kennet Jane , Wicker Linda S , Bond Simon , Todd John A , Waldron-Lynch Frank 
Published: December 2015

IntroductionType 1 diabetes (T1D) is caused by autoimmune destruction of the insulin-producing β cells in the pancreatic islets, leading to insulinopenia and hyperglycaemia. Genetic analyses indicate that alterations of the interleukin-2 (IL-2) pathway mediating immune activation and tolerance predispose to T1D, specifically the polymorphic expression of the IL-2 receptor-α chain (CD25) on T lymphocytes. Replacement of physiological doses of IL-2 could restore self-tolerance and prevent further autoimmunity by enhancing the function of CD4+T regulatory cells (Tregs) to limit the activation of auto reactive T effector cells (Teffs). In this experimental medicine study, we use an adaptive trial design to determine the optimal dosing regimen for IL-2 to improve Treg function while limiting activation of Teffs in participants with T1D.Methods and analysisTheAdaptive study ofIL-2 dosefrequencyon Tregs in type 1 diabetes(DILfrequency) is a mechanistic, non-randomised, repeat dose open-label, response-adaptive study of 36 participants with T1D. The objective is to establish the optimal dose and frequency of ultra-low dose IL-2: to increase Treg frequency within the physiological range, to increase CD25 expression on Tregs, without increasing CD4+Teffs. DILfrequency has an initial learning phase where 12 participants are allocated to six different doses and frequencies followed by an interim statistical analysis. After analysis of the learning phase, the Dose and Frequency Committee will select the optimal targets for Treg frequency, Treg CD25 expression and Teff frequency. Three groups of eight participants will be treated consecutively in the confirming phase. Each dose and frequency selected will be based on statistical analysis of all data collected from the previous groups.EthicsEthical approval for DILfrequency was granted on 12 August 2014.ResultsThe results of this study will be reported, through peer-reviewed journals, conference presentations and an internal organisational report.Trial registration numbersNCT02265809,ISRCTN40319192, CRN17571.
Do US thyroid cancer incidence rates increase with socioeconomic status among people with health insurance? An observational study using SEER population-based data
Authors: Altekruse Sean , Das Anita , Cho Hyunsoon , Petkov Valentina , Yu Mandi 
Published: December 2015

ObjectivesThe US thyroid cancer incidence rates are rising while mortality remains stable. Trends are driven by papillary thyroid cancer (PTC), the predominant cancer subtype which has a very good prognosis. We hypothesised that health insurance and high census tract socioeconomic status (SES) are associated with PTC risk.DesignRelationships between thyroid cancer incidence, insurance and census tract SES during 2007–2010 were examined in population-based cancer registries. Cases were stratified by tumour histology, size and demography.SettingSurveillance, Epidemiology, and End Results (SEER) registries covering 30% of the US population.ResultsPTCs accounted for 88% of incident thyroid cancer cases. Small PTCs (≤2 cm) accounted for 60% of cases. Unlike non-PTC cases, the majority of those diagnosed with PTC were <50 years of age and had ≤2 cm tumours. Rate ratios (RR) of PTC diagnoses increased monotonically with SES among fully insured cases. The effect was strongest for small PTCs, high-SES versus low-SES quintile RR=2.7, 95% CI 2.6 to 2.9, two-sided trend test p<0.0001. For small PTC cases with insurance, the monotonic increase in incidence rates with rising SES persisted among cases younger than 50 years of age (RR=3.3, 95% CI 3.0 to 3.5), women (RR=2.6, 95% CI 2.5 to 2.8) and Caucasians (RR=2.5, 95% CI 2.4 to 2.7). Among the less than fully insured, rates generally decreased with increasing SES.ConclusionsThe >2.5-fold increase in risk of PTC diagnosis among insured individuals associated with high SES may be informative with respect to the contemporary issue of PTC overdiagnosis.
Ciprofloxacin DPI: a randomised, placebo-controlled, phase IIb efficacy and safety study on cystic fibrosis
Authors: Dorkin Henry L , Staab Doris , Operschall Elisabeth , Alder Jeff , Criollo Margarita 
Published: December 2015

BackgroundTreatment of infective bronchitis involvingPseudomonas aeruginosais a cornerstone of care in patients with cystic fibrosis (CF). This phase IIb, randomised, double-blind, placebo-controlled study assessed the efficacy and safety of ciprofloxacin dry powder for inhalation (DPI) in this population.MethodsPatients with CF, ≥12 years of age (N=286), were randomised to ciprofloxacin DPI (32.5 mg (n=93) or 48.75 mg (n=93)), or corresponding placebo (32.5 mg, n=65; 48.75 mg, n=35) twice daily for 28 days. The primary objective was the change in forced expiratory volume in 1 s (FEV1) from baseline (day 0) to end of treatment (day 29) in the intent-to-treat population for ciprofloxacin DPI compared with the corresponding placebo group.ResultsThe primary effectiveness objective was not met; there were no significant differences in change in FEV1 between ciprofloxacin DPI and the corresponding placebo group for either dose (p=0.154). However, in pooled analyses, FEV1 decline from baseline to treatment end was significantly lower with ciprofloxacin DPI than with placebo (pooled data; p=0.02). Ciprofloxacin DPI showed positive effects on sputum bacterial load and quality of life, but these effects were not maintained at the 4-week follow-up. Ciprofloxacin DPI was well tolerated and there were no significant differences in type/incidence of treatment-emergent adverse events by treatment group (p=0.115).ConclusionsFurther investigations are needed to determine the full scope of the beneficial effects of ciprofloxacin DPI for patients with CF.Trial registration numberClinicaltrials.govNCT00645788; EudraCT 2008-008314-40.
Selective estrogen receptor modulators and betulinic acid act synergistically to target ERα and SP1 transcription factor dependent Pygopus expression in breast cancer
Authors: Tzenov Youlian R , Andrews Phillip , Voisey Kim , Gai Luis , Carter Beverley , Whelan Kathryn , Popadiuk Catherine , Kao Kenneth R 
Published: December 2015

AimsEstrogen and progesterone hormone receptor (ER and PR) expression in invasive breast cancer predicts response to hormone disruptive therapy.Pygopus2 (hPYGO2) encodes a chromatin remodelling protein important for breast cancer growth and cell cycle progression. The aims of this study were to determine the mechanism of expression of hPYGO2in breast cancer and to examine how this expression is affected therapeutically.MethodshPYGO2 and ER protein expression was examined in a breast tumour microarray by immunohistochemistry. hPYGO2 RNA and protein expression was examined in ER+ and ER− breast cancer cell lines in the presence of selective estrogen hormone receptor modulator drugs and the specificity protein-1 (SP1) inhibitor, betulinic acid (BA). The effects of these drugs on the ability for ER and SP1 to bind the hPYGO2promoter and affect cell cycle progression were studied using chromatin immunoprecipitation assays.ResultshPYGO2 was expressed in seven of eight lines and in nuclei of 98% of 65 breast tumours, including 3 Ductal carcinoma in situ and 62 invasive specimens representing ER-negative (22%) and ER-positive (78%) cases. Treatment with either 4-Hydroxytamoxifen (OHT) or fulvestrant reduced hPYGO2 mRNA 10-fold and protein 5–10-fold within 4 h. Promoter analysis indicated an ER/SP1 binding site at nt −225 to −531 of hPYGO2. SP1 RNA interference and BA reduced hPYGO2 protein and RNA expression by fivefold in both ER- and ER+ cells. Further attenuation was achieved by combining BA and 4-OHT resulting in eightfold reduction in cell growth.ConclusionsOur findings reveal a mechanistic link between hormone signalling and the growth transcriptional programme. The activation of its expression by ERα and/or SP1 suggests hPYGO2 as a theranostic target for hormone therapy responsive and refractory breast cancer.
Políticas de Controle da Desordem Urbana: A Experiência das Unidades de Ordem Pública na Cidade do Rio de Janeiro
Authors: Carneiro Leandro Piquet , Bondarovsky Bruno 
Published: December 2015

<p>Este artigo descreve e analisa o processo de desenho e execução das Unidades de Ordem Pública (UOP) na Cidade do Rio de Janeiro. Trata-se de um programa desenvolvido por gestores locais da Secretaria Municipal da Ordem Pública com a participação de pesquisadores do Núcleo de Pesquisa de Políticas Públicas da Universidade de São Paulo entre 2010 e 2013. As oito Unidades de Ordem Pública instaladas permitiram testar em pequena escala novos modelos de operação, gestão e controle da ordem pública no município. São descritas as características, ações, custos e operações do programa, com a apresentação de dados e informações que indicam seus efeitos, assim como as possibilidades de manutenção, ampliação e disseminação.</p>
Cenário de Práticas para a Formação Universitária: O Olhar dos Estudantes
Authors: Cervato-Mancuso Ana Maria , Nunes Nadine Marques , Andrade Elisabete Agrela de 
Published: December 2015

<p>A Educação Universitária tem como desafio atual o aprimoramento de suas práticas pedagógicas. O objetivo do presente trabalho foi conhecer os valores e significados atribuídos, por estudantes do curso de Nutrição da USP, às suas experiências de extensão universitária. Trata-se de um estudo de abordagem qualitativa, utilizando-se o grupo focal como técnica de coleta de dados. Foram realizados cinco grupos, divididos entre as principais atividades realizadas: Empresa Júnior, Iniciação Científica, Associação Atlética, Clínica de Nutrição e Jornada Universitária. Verifica-se que os estudantes consideraram que cada atividade colabora com o desenvolvimento de competência ou habilidade profissional específica. Dentre elas, destacam-se: autonomia, autoconfiança, comunicação interpessoal, comunicação social, trabalho em equipe, visão ampliada dos problemas e das necessidades sociais, conhecimento técnico e teórico específico, atenção integral, contato com a realidade profissional, entre outras. Conclui-se que as atividades de extensão universitária contribuem tanto para que, especificamente na área da saúde, os projetos pedagógicos sejam flexíveis para a incorporação dessas atividades.</p>
Search for Rare Copy-Number Variants in Congenital Heart Defects Identifies Novel Candidate Genes and a Potential Role for FOXC1 in Patients With Coarctation of the Aorta
Authors: Sanchez-Castro Marta , Eldjouzi Hadja , Charpentier Eric , Busson Pierre-François , Hauet Quentin , Lindenbaum Pierre , Delasalle-Guyomarch Béatrice , Baudry Adrien , Pichon Olivier , Pascal Cécile , Lefort Bruno , Bajolle Fanny , Pezard Philippe , Schott Jean-Jacques , Dina Christian , Redon Richard , Gournay Véronique , Bonnet Damien , Le Caignec Cédric 
Published: December 2015

Background—
Congenital heart defects are the most frequent malformations among newborns and a frequent cause of morbidity and mortality. Although genetic variation contributes to congenital heart defects, their precise molecular bases remain unknown in the majority of patients.

Methods and Results—

We analyzed, by high-resolution array comparative genomic hybridization, 316 children with sporadic, nonsyndromic congenital heart defects, including 76 coarctation of the aorta, 159 transposition of the great arteries, and 81 tetralogy of Fallot, as well as their unaffected parents. We identified by array comparative genomic hybridization, and validated by quantitative real-time polymerase chain reaction, 71 rare de novo (n=8) or inherited (n=63) copy-number variants (CNVs; 50 duplications and 21 deletions) in patients. We identified 113 candidate genes for congenital heart defects within these CNVs, including
BTRC
,
CHRNB3
,
CSRP2BP
,
ERBB2
,
ERMARD
,
GLIS3
,
PLN
,
PTPRJ
,
RLN3
, and
TCTE3
. No de novo CNVs were identified in patients with transposition of the great arteries in contrast to coarctation of the aorta and tetralogy of Fallot (
P
=0.002; Fisher exact test). A search for transcription factor binding sites showed that 93% of the rare CNVs identified in patients with coarctation of the aorta contained at least 1 gene with FOXC1-binding sites. This significant enrichment (
P
<0.0001; permutation test) was not observed for the CNVs identified in patients with transposition of the great arteries and tetralogy of Fallot. We hypothesize that these CNVs may alter the expression of genes regulated by FOXC1. Foxc1 belongs to the forkhead transcription factors family, which plays a critical role in cardiovascular development in mice.

Conclusions—

These data suggest that deregulation of
FOXC1
or its downstream genes play a major role in the pathogenesis of coarctation of the aorta in humans.
Factors Affecting Bleeding and Stent Thrombosis in Clinical Trials Comparing Bivalirudin With Heparin During Percutaneous Coronary Intervention
Authors: Bittl John A. , He Yulei , Lang Christopher D. , Dangas George D. 
Published: December 2015

Background—
Patients treated with bivalirudin in randomized clinical trials of percutaneous coronary intervention generally have less bleeding but more acute stent thrombosis (ST) than do patients treated with heparin, but differences have varied among trials.

Methods and Results—
We modeled the risk of major hemorrhage and ischemic outcomes 30 days after percutaneous coronary intervention by treatment assignment and the use of adjunctive therapies in 18 randomized clinical trials enrolling 41 871 patients. Overall bivalirudin caused less major bleeding (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.53–0.76), more ST (OR, 1.58; 95% CI, 1.19–2.09), and no difference in mortality (OR, 0.93; 95% CI, 0.77–1.14) than heparin. A risk–benefit analysis identified 19 fewer bleeds and 5 more STs for every 1000 patients treated with bivalirudin in place of heparin. No significant bleeding advantage of bivalirudin over heparin could be identified in randomized clinical trials when transradial access (OR, 0.89; 95% CI, 0.57–1.41) and planned glycoprotein IIb/IIIa inhibitors were used with bivalirudin in the majority of patients (OR, 1.07; 95% CI, 0.87–1.31). The use of prasugrel or ticagrelor eliminated bleeding differences (OR, 0.80; 95% CI, 0.63–1.03) but did not reduce the risk of ST after bivalirudin (OR, 2.20; 95% CI, 1.48–3.27).

Conclusions—

Substituting bivalirudin for heparin conferred a tradeoff between bleeding and ST. Transradial access, adjunctive glycoprotein IIb/IIIa inhibitors, and potent P2Y
12
inhibitors attenuated the bleeding advantage of bivalirudin over heparin but had no apparent effect on early ST. New approaches to reduce bleeding and ischemic complications during percutaneous coronary intervention warrant further investigation.
Risk of Adverse Cardiac and Bleeding Events Following Cardiac and Noncardiac Surgery in Patients With Coronary Stent
Authors: Saia Francesco , Belotti Laura Maria Beatrice , Guastaroba Paolo , Berardini Alessandra , Rossini Roberta , Musumeci Giuseppe , Tarantini Giuseppe , Campo Gianluca , Guiducci Vincenzo , Tarantino Fabio , Menozzi Alberto , Varani Elisabetta , Santarelli Andrea , Tondi Stefano , De Palma Rossana , Rapezzi Claudio , Marzocchi Antonio 
Published: December 2015

Background—
Epidemiology and consequences of surgery in patients with coronary stents are not clearly defined, as well as the impact of different stent types in relationship with timing of surgery.

Methods and Results—
Among 39 362 patients with previous coronary stenting enrolled in a multicenter prospective registry and followed for 5 years, 13 128 patients underwent 17 226 surgical procedures. The cumulative incidence of surgery at 30 days, 6 months, 1 year, and 5 years was 3.6%, 9.4%, 14.3%, and 40.0%, respectively, and of cardiac and noncardiac surgery was 0.8%, 2.1%, 2.6%, and 4.0% and 1.3%, 5.1%, 9.1%, and 31.7%, respectively. We assessed the incidence and the predictors of cardiac death, myocardial infarction, and serious bleeding event within 30 days from surgery. Cardiac death occurred in 438 patients (2.5%), myocardial infarction in 256 (1.5%), and serious bleeding event in 1099 (6.4%). Surgery increased 1.58× the risk of cardiac death during follow-up. Along with other risk factors, the interplay between stent type and time from percutaneous coronary intervention to surgery was independently associated with cardiac death/myocardial infarction. In comparison with bare-metal stent implanted >12 months before surgery, old-generation drug-eluting stent was associated with higher risk of events at any time point. Conversely, new-generation drug-eluting stent showed similar safety as bare-metal stent >12 months and between 6 and 12 months and appeared trendly safer between 0 and 6 months.

Conclusions—
Surgery is frequent in patients with coronary stents and carries a considerable risk of ischemic and bleeding events. Ischemic risk is inversely related with time from percutaneous coronary intervention to surgery and is influenced by stent type.