bluuebunny/crossref_metadata_2025_split huggingface dataset:
Measuring relational aspects of hospital care in England with the ‘Patient Evaluation of Emotional Care during Hospitalisation’ (PEECH) survey questionnaire
Authors: Murrells Trevor , Robert Glenn , Adams Mary , Morrow Elizabeth , Maben Jill 
Published: February 2013

ObjectivesTo first, validate in English hospitals the internal structure of the ‘Patient Evaluation of Emotional Care during Hospitalisation’ (PEECH) survey tool which was developed in Australia and, second, to examine how it may deepen the understanding of patient experience through comparison with results from the Picker Patient Experience Questionnaire (PPE-15).DesignA 48-item survey questionnaire comprising both PEECH and PPE-15 was fielded. We performed exploratory factor analysis and then confirmatory factor analysis using a number of established fit indices. The external validity of the PEECH factor scores was compared across four participating services and at the patient level, factor scores were correlated with the PPE-15.SettingFour hospital services (an Emergency Admissions Unit; a maternity service; a Medicine for the Elderly department and a Haemato-oncology service) that contrasted in terms of the reported patient experience performance.ParticipantsSelection of these acute service settings was based on achieving variation of the following factors: teaching hospital/district general hospital, urban/rural locality and high-performing/low-performing organisations (using results of annual national staff and patient surveys). A total of 423 surveys were completed by patients (26% response rate).ResultsA different internal structure to the PEECH instrument emerged in English hospitals. However, both the existing and new factor models were similar in terms of fit. The correlations between the new PEECH factors and the PPE-15 were all in the expected direction, but two of the new factors (personal interactions and feeling valued) were more strongly associated with the PPE-15 than the remaining two factors (feeling informed and treated as an individual).ConclusionsPEECH can help to build an understanding of complex interpersonal aspects of quality of care, alongside the more transactional and functional aspects typically captured by PPE-15. Further testing of the combined instrument should be undertaken in a wider range of healthcare settings.
The utility of copeptin in the emergency department as a predictor of adverse outcomes in non-ST-elevation acute coronary syndrome: the COPED-PAO study
Authors: Sánchez Miquel , Llorens Pere , Herrero Pablo , Martín-Sanchez F Javier , Piñera Pascual , Miró Òscar ,   on behalf of COPEP study investigators
Published: February 2013

AimsTo test the utility of a single copeptin determination at presentation to the emergency department (ED) as a short-term prognosis marker in patients with non-ST-elevation acute coronary syndrome (NSTEACS). To compare the results with those achieved with conventional troponin.MethodsA multicentric, prospective, observational, longitudinal, cohort study involving 15 Spanish EDs. Inclusion: consecutive patients with chest pain (<12 h) finally diagnosed of NSTEACS. Measurements: copeptin and troponin at arrival. Cut-off point for copeptin: 25.9 pmol/l. Follow-up: within 2 months after ED attendance to identify 30-day adverse events. Discriminatory capacity of copeptin and troponin was compared by receiver operating characteristic (ROC) curves.ResultsWe included 377 patients with NSTEACS. Adverse events: 11 (2.9%) patients died, 27 (7.2%) had an adverse coronary event, 14 (3.7%) had a stroke, and 48 (12.7%) a composite endpoint. The initial copeptine value was over 25.9 pmol/l in 114 patients, and they presented a higher mortality rate (OR: 4.2, (95% CI 1.2 to 14.8); p=0.03). This association disappeared after adjusting by clinical variables or troponin level. No significant differences were found for the remaining endpoints. The area under the curve of the ROC curve of 30-day mortality was 0.73 (95% CI 0.58 to 0.87) for copeptin, and 0.80 (95% CI 0.73 to 0.87) for troponin.ConclusionsIn patients with NSTEACS, determination of copeptin at presentation to the ED is associated with risk of death during the subsequent month. This association, however, disappears after adjusting by baseline features or troponin level, so copeptin does not add complementary prognostic information over that provided by troponin.
Should we customise critical value procedure according to patient origin and laboratory turnaround time?
Authors: Salinas Maria , López-Garrigós Maite , Gutiérrez Mercedes , Lugo Javier , Flors Lucia , Leiva-Salinas Carlos 
Published: February 2013

IntroductionOur routine laboratory critical value notification procedure is based on a short list of six fundamental critical values. The report system for our Stat laboratory is not based on this ‘short list’; instead, critical values are always reported according to the patient clinical context and the previous laboratory results. The aim of our work is to show how a critical value notification procedure based on a rigid list of values and thresholds can result in completely different results depending on whether the tests are requested in a stat or a routine manner.Material and methodsWe reviewed the number of critical value notifications based on the short list for the routine laboratory. For the stat laboratory, we studied the number of real notifications based on the pathologist validation of the individualised situation of the patient and calculated the number of notifications that would have been reported if the routine short list would have been used instead.ResultsThe number of critical values that would have been reported if using the routine short list in stat laboratory was high when compared with the number of critical values that were really reported.ConclusionsUsing a rigid list of laboratory values to notify critical values resulted in completely different results depending on whether the tests were requested in stat or routine. Reporting only really unexpected values through an individual custom-made reporting procedure may avoid the wasting of time and resources and raising false alarms among referring physicians and patients.
Geologically-based permeability anisotropy estimates for tidally-influenced reservoirs using quantitative shale data
Authors: Burton D. , Wood L.J. 
Published: February 2013

The effect of the vertical to horizontal permeability ratio (

k
v

/

k
h

) on many displacement properties is significant, making it an important parameter to estimate for reservoir models. Simple ‘streamline’ models have been developed which relate

k
v

/

k
h

at the reservoir scale to shale geometry, fraction and vertical frequency. A limitation of these models, especially for tidally-influenced reservoirs, is the lack of quantitisative geological inputs.

To address this lack of data, detailed shale characteristics were measured, using Lidar point clouds, from four different tidally-influenced reservoir analogues: estuarine point bar (McMurray Formation, Alberta, Canada), tidal sand ridge (Tocito Sandstone, New Mexico), as well as both unconfined and confined tidal bars (Sego Sandstone, Utah). Estuarine point bars have long (
x̄
= 67.8 m) shales that are thick and frequent relative to the other units. Tidal sand ridges have short shales (
x̄
= 8.6 m dip orientation) that are thin and frequent. Confined tidal bars contain shales that are thin, infrequent and anisotropic (x–  = 16.3 m dip orientation). Unconfined tidal bars contain nearly equidimensional shales of intermediate length (
x̄
= 18.6 m dip orientation) with moderate thicknesses and vertical frequency.

The unique shale character of each unit results in a different distribution of estimated

k
v

/

k
h

values. Estuarine point bars have lower average

k
v

/

k
h

values (
x̄
= 8.2 ×10
−4
) than any other setting because of the long shales they contain. Tidal sand ridges have short, but frequent shales, which results in moderate

k
v

/

k
h

estimates (
x̄
= .011). Estimates of

k
v

/

k
h

are typically highest in confined tidal bars (
x̄
= .038), which contain anisotropic and infrequent shales. Unconfined tidal bars have moderate lengths and frequency resulting in

k
v

/

k
h

estimates averaging 0.004. The results of this study highlight the link between heterogeneity, reservoir architecture and flow parameters.
Integrated tectonic basin modelling as an aid to understanding deep-water rifted continental margin structure and location
Authors: Roberts Alan M. , Kusznir Nick J. , Corfield Richard I. , Thompson Mark , Woodfine Richard 
Published: February 2013

An integrated workflow has been devised for the investigation of deep-water rifted continental margins. At a margin this allows us to predict the crustal structure, the distribution of continental-lithosphere thinning and the location of the ocean–continent transition with a new degree of confidence. The workflow combines the analytical techniques of 2D or 3D gravity inversion, 2D or 3D flexural backstripping with reverse thermal subsidence modelling, upper-crustal fault analysis and rifted margin forward modelling. No one technique on its own can provide all of the required answers, nor can it provide answers without some degree of uncertainty. The use of a combination of techniques, however, provides answers to several different problems and, crucially, more confidence in these answers.
The workflow provides direct information on the present-day geometry of rifted margins and leads towards a better understanding of the geodynamic evolution of these margins. It also provides information which can inform the exploration process by making predictions about crustal structure at the ocean–continent transition, the location of the continent–ocean boundary, stretching-factor, heat-flow magnitude and history, palaeobathymetric history and subsurface palaeostructure. Application of the workflow is illustrated here with reference to the continental margins of West India, Brazil, West Australia, Norway and Newfoundland–Iberia.
Sirtuin-1 Regulates Acinar-to-Ductal Metaplasia and Supports Cancer Cell Viability in Pancreatic Cancer
Authors: Wauters Elke , Sanchez-Arévalo Lobo Victor J. , Pinho Andreia V. , Mawson Amanda , Herranz Daniel , Wu Jianmin , Cowley Mark J. , Colvin Emily K. , Njicop Erna Ngwayi , Sutherland Rob L. , Liu Tao , Serrano Manuel , Bouwens Luc , Real Francisco X. , Biankin Andrew V. , Rooman Ilse 
Published: February 2013

Abstract
The exocrine pancreas can undergo acinar-to-ductal metaplasia (ADM), as in the case of pancreatitis where precursor lesions of pancreatic ductal adenocarcinoma (PDAC) can arise. The NAD+-dependent protein deacetylase Sirtuin-1 (Sirt1) has been implicated in carcinogenesis with dual roles depending on its subcellular localization. In this study, we examined the expression and the role of Sirt1 in different stages of pancreatic carcinogenesis, i.e. ADM models and established PDAC. In addition, we analyzed the expression of KIAA1967, a key mediator of Sirt1 function, along with potential Sirt1 downstream targets. Sirt1 was co-expressed with KIAA1967 in the nuclei of normal pancreatic acinar cells. In ADM, Sirt1 underwent a transient nuclear-to-cytoplasmic shuttling. Experiments where during ADM, we enforced repression of Sirt1 shuttling, inhibition of Sirt1 activity or modulation of its expression, all underscore that the temporary decrease of nuclear and increase of cytoplasmic Sirt1 stimulate ADM. Our results further underscore that important transcriptional regulators of acinar differentiation, that is, Pancreatic transcription factor-1a and β-catenin can be deacetylated by Sirt1. Inhibition of Sirt1 is effective in suppression of ADM and in reducing cell viability in established PDAC tumors. KIAA1967 expression is differentially downregulated in PDAC and impacts on the sensitivity of PDAC cells to the Sirt1/2 inhibitor Tenovin-6. In PDAC, acetylation of β-catenin is not affected, unlike p53, a well-characterized Sirt1-regulated protein in tumor cells. Our results reveal that Sirt1 is an important regulator and potential therapeutic target in pancreatic carcinogenesis. Cancer Res; 73(7); 2357–67. ©2012 AACR.
Prevalence and Healthcare Actions of Women in a Large Health System with a Family History Meeting the 2005 USPSTF Recommendation for BRCA Genetic Counseling Referral
Authors: Bellcross Cecelia A. , Leadbetter Steven , Alford Sharon Hensley , Peipins Lucy A. 
Published: February 2013

Abstract
Background: In 2005, the United States Preventive Services Task Force (USPSTF) released guidelines which outlined specific family history patterns associated with an increased risk for BRCA1/2 mutations, and recommended at-risk individuals be referred for genetic counseling and evaluation for BRCA testing. The purpose of this study was to assess the prevalence of individuals with a USPSTF increased-risk family history pattern, the frequency with which specific patterns were met, and resulting healthcare actions among women from the Henry Ford Health System.
Methods: As part of a study evaluating ovarian cancer risk perception and screening, 2,524 randomly selected participants completed a detailed interview (response rate 76%) from an initial eligible cohort of 16,720 women.
Results: Approximately 6% of participants had a family history fulfilling one or more of the USPSTF patterns. Although 90% of these women had shared their family history with their provider, less than 20% had been referred for genetic counseling and only 8% had undergone genetic testing. Caucasian women with higher income and education levels were more likely to receive referrals. Among the 95 participants in the total study cohort who reported BRCA testing, 78% did not have a family history that met one of the USPSTF patterns.
Conclusions: These results suggest a higher prevalence of women with an increased-risk family history than originally predicted by the USPSTF, and lack of provider recognition and referral for genetic services.
Impact: Improvements in healthcare infrastructure and clinician education will be required to realize population level benefits from BRCA genetic counseling and testing. Cancer Epidemiol Biomarkers Prev; 22(4); 728–35. ©2013 AACR.
EGFR Exon 20 Insertion Mutations in Lung Adenocarcinomas: Prevalence, Molecular Heterogeneity, and Clinicopathologic Characteristics
Authors: Arcila Maria E. , Nafa Khedoudja , Chaft Jamie E. , Rekhtman Natasha , Lau Christopher , Reva Boris A. , Zakowski Maureen F. , Kris Mark G. , Ladanyi Marc 
Published: February 2013

Abstract
In contrast to other primary epidermal growth factor receptor (EGFR) mutations in lung adenocarcinomas, insertions in exon 20 of EGFR have been generally associated with resistance to EGFR-tyrosine kinase inhibitors. Their molecular spectrum, clinicopathologic characteristics, and prevalence are not well established. Tumors harboring EGFR exon 20 insertions were identified through an algorithmic screen of 1,500 lung adenocarcinomas. Cases were first tested for common mutations in EGFR (exons 19 and 21) and KRAS (exon 2) and, if negative, further analyzed for EGFR exon 20 insertions. All samples underwent extended genotyping for other driver mutations in EGFR, KRAS, BRAF, ERBB2/HER2, NRAS, PIK3CA, MEK1, and AKT by mass spectrometry; a subset was evaluated for ALK rearrangements. We identified 33 EGFR exon 20 insertion cases [2.2%, 95% confidence interval (CI), 1.6–3.1], all mutually exclusive with mutations in the other genes tested (except PIK3CA). They were more common among never-smokers (P &lt; 0.0001). There was no association with age, sex, race, or stage. Morphologically, tumors were similar to those with common EGFR mutations but with frequent solid histology. Insertions were highly variable in position and size, ranging from 3 to 12 bp, resulting in 13 different insertions, which, by molecular modeling, are predicted to have potentially different effects on erlotinib binding. EGFR exon 20 insertion testing identifies a distinct subset of lung adenocarcinomas, accounting for at least 9% of all EGFR-mutated cases, representing the third most common type of EGFR mutation after exon 19 deletions and L858R. Insertions are structurally heterogeneous with potential implications for response to EGFR inhibitors. Mol Cancer Ther; 12(2); 220–9. ©2012 AACR.
A Human Single-Domain Antibody Elicits Potent Antitumor Activity by Targeting an Epitope in Mesothelin Close to the Cancer Cell Surface
Authors: Tang Zhewei , Feng Mingqian , Gao Wei , Phung Yen , Chen Weizao , Chaudhary Amit , Croix Brad St. , Qian Min , Dimitrov Dimiter S. , Ho Mitchell 
Published: February 2013

Abstract
Monoclonal antibodies against mesothelin are being evaluated for the treatment of mesothelioma and multiple forms of cancers, and show great promise for clinical development for solid cancers. Antibodies against mesothelin have been shown to act via immunotoxin-based inhibition of tumor growth and induction of antibody-dependent cell-mediated cytotoxicity (ADCC). However, complement-dependent cytotoxicity (CDC), considered an important additional mechanism of therapeutic antibodies against tumors, is inactive for such antibodies. Here, we used phage display antibody engineering technology and synthetic peptide screening to identify SD1, a human single-domain antibody to mesothelin. SD1 recognizes a conformational epitope at the C-terminal end (residues 539–588) of mesothelin close to the cell surface. To investigate SD1 as a potential therapeutic agent, we generated a recombinant human Fc (SD1-hFc) fusion protein. Interestingly, the SD1-hFc protein exhibits strong CDC activity, in addition to ADCC, against mesothelin-expressing tumor cells. Furthermore, it causes growth inhibition of human tumor xenografts in nude mice as a single agent. SD1 is the first human single-domain antibody targeting mesothelin-expressing tumors, shows potential as a cancer therapeutic candidate, and may improve current antibody therapy targeting mesothelin-expressing tumors. Mol Cancer Ther; 12(4); 416–26. ©2013 AACR.
Quantitative Chemical Proteomics Profiling Differentiates Erlotinib from Gefitinib inEGFRWild-Type Non–Small Cell Lung Carcinoma Cell Lines
Authors: Augustin Angélique , Lamerz Jens , Meistermann Hélène , Golling Sabrina , Scheiblich Stefan , Hermann Johannes C. , Duchateau-Nguyen Guillemette , Tzouros Manuel , Avila David W. , Langen Hanno , Essioux Laurent , Klughammer Barbara 
Published: February 2013

AbstractAlthough both erlotinib and gefitinib target the EGF receptor (EGFR), erlotinib is effective in patients with EGFR wild-type or mutated tumors, whereas gefitinib is only beneficial for patients with activating mutations. To determine whether these differences in clinical outcomes can be attributed to their respective protein interaction profiles, a label-free, quantitative chemical proteomics study was conducted. Using this method, 24 proteins were highlighted in the binding profiles of erlotinib and gefitinib. Unlike gefinitib, erlotinib displaced the ternary complex formed by integrin-linked kinase (ILK), α-parvin, and PINCH (IPP). The docking of erlotinib in the three-dimensional structure of ILK showed that erlotinib has the ability to bind to the ATP-binding site, whereas gefitinib is unlikely to bind with high affinity. As the IPP complex has been shown to be involved in epithelial-to-mesenchymal transition (EMT) and erlotinib sensitivity has been correlated with EMT status, we used a cellular model of inducible transition and observed that erlotinib prevented EMT in a more efficient way than gefitinib by acting on E-cadherin expression as well as on IPP levels. A retrospective analysis of the MERIT trial indicated that, besides a high level of E-cadherin, a low level of ILK could be linked to clinical benefit with erlotinib. In conclusion, we propose that, in an EGFR wild-type context, erlotinib may have a complementary mode of action by inhibiting IPP complex activities, resulting in the slowing down of the metastatic process of epithelial tumors. Mol Cancer Ther; 12(4); 520–9. ©2013 AACR.
The Role of Platelet-Endothelial Cell Adhesion Molecule-1 in Atheroma Formation Varies Depending on the Site-Specific Hemodynamic Environment
Authors: Harrison Matthew , Smith Emily , Ross Ewan , Krams Robert , Segers Dolf , Buckley Christopher D. , Nash Gerard B. , Rainger G. Ed 
Published: February 2013

Objective—
Polymorphisms in the platelet-endothelial cell adhesion molecule (PECAM-1)-1 gene are linked to increased risk of coronary artery disease. Because PECAM-1 has been demonstrated to form a mechanosensory complex that can modulate inflammatory responses in murine arterial endothelial cells, we hypothesized that PECAM-1 contributes to atherogenesis in a shear-dependent and site-specific manner.

Approach and Results—

ApoE
–/–
mice that were wild-type, heterozygous, or deficient in PECAM-1 were placed on a high-fat diet. Detailed analysis of the aorta at sites with differing hemodynamics revealed that PECAM-1–deficient mice had reduced disease in areas of disturbed flow, whereas plaque burden was increased in areas of steady, laminar flow. In concordance with these observations, bone marrow chimera experiments revealed that hematopoietic PECAM-1 resulted in accelerated atheroma formation in areas of laminar and disturbed flow, however endothelial PECAM-1 moderated disease progression in areas of high sheer stress. Moreover, using shear stress–modifying carotid cuffs, PECAM-1 was shown to promote macrophage recruitment into lesions developing in areas of low shear stress.

Conclusions—
PECAM-1 on bone marrow cells is proatherogenic irrespective of the hemodynamic environment, however endothelial cell PECAM-1 is antiatherogenic in high shear environments. Thus, targeting this pathway therapeutically would require a cell-type and context-specific strategy.
Genetic Determination of Plasma Cholesterol Efflux Capacity Is Gender-Specific and Independent of HDL-Cholesterol Levels
Authors: Villard Elise F. , EI Khoury Petra , Frisdal Eric , Bruckert Eric , Clement Karine , Bonnefont-Rousselot Dominique , Bittar Randa , Le Goff Wilfried , Guerin Maryse 
Published: February 2013

Objective—
We investigated the impact of several genetic variants located in genes encoding for proteins involved in biogenesis, maturation, and intravascular remodeling of high density lipoprotein (HDL) particles on plasma efflux capacity.

Approach and Results—

The capacity of whole-plasma to mediate cholesterol efflux from cholesterol-loaded human THP-1 macrophages was measured in 846 individuals (450 men and 396 women). We demonstrated that rs17231506 (
CETP
c.–1337 C>T), rs2230806 (
ABCA1
p.R219K), rs1799837 (
APOA1
c.–75 G>A), rs5086 (
APOAII
c.–265 T>C), and rs1800588 (
LIPC
c.–514 C>T) single nucleotide polymorphisms (SNPs) significantly modulate the capacity of whole-plasma to mediate cholesterol efflux from human macrophages in a sex-dependent manner. Such associations were independent of circulating plasma lipid levels (HDL-cholesterol, triglyceride, low density lipoprotein-cholesterol). In women, we identified the
APOA1
c.–75 G>A and the
LIPC
c.–514 C>T variants as major contributors of interindividual variability of plasma efflux capacity, whereas the
ABCA1
p.R219K and the
APOAII
c.–265 T>C SNPs mostly contribute to total variance of plasma efflux capacity in men. Multiple regression analyses revealed that the 7 SNPs tested accounted together for approximately 6% of total plasma efflux capacity. We demonstrated that genetically determined plasma efflux capacity represents a better predictor of macrophage cholesterol removal, as compared with plasma HDL-cholesterol levels.

Conclusions—
Genetic variants located within genes encoding proteins involved in HDL metabolism significantly impact plasma efflux capacity independently of variation in plasma HDL-cholesterol levels.