bluuebunny/crossref_metadata_2025_split huggingface dataset:
What components of chronic care organisation relate to better primary care for coronary heart disease patients? An observational study
Authors: van Lieshout Jan , Frigola Capell Eva , Ludt Sabine , Grol Richard , Wensing Michel 
Published: August 2012

ObjectivesCardiovascular risk management (CVRM) received by patients shows large variation across countries. In this study we explored the aspects of primary care organisation associated with key components of CVRM in coronary heart disease (CHD) patients.DesignObservational study.Setting273 primary care practices in Austria, Belgium, England, Finland, France, Germany, The Netherlands, Slovenia, Switzerland and Spain.ParticipantsA random sample of 4563 CHD patients identified by coded diagnoses in eight countries, based on prescription lists and while visiting the practice in one country each.Main outcome measureWe performed an audit in primary care practices in 10 European countries. We used six indicators to measure key components of CVRM: risk factor recording, antiplatelet therapy, influenza vaccination, blood pressure levels (systolic <140 and diastolic <90 mm Hg), and low-density lipoprotein cholesterol <2.5 mmol/l. Data from structured questionnaires were used to construct an overall measure and six domain measures of practice organisation based on 39 items. Using multilevel regression analyses we explored the effects of practice organisation on CVRM, controlling for patient characteristics.ResultsBetter overall organisation of a primary care practice was associated with higher scores on three indicators: risk factor registration (B=0.0307, p<0.0001), antiplatelet therapy (OR 1.05, p=0.0245) and influenza vaccination (OR 1.12, p<0.0001). Overall practice organisation was not found to be related with recorded blood pressure or cholesterol levels. Only the organisational domains ‘self-management support’ and ‘use of clinical information systems’ were linked to three CVRM indicators.ConclusionsA better organisation of a primary care practice was associated with better scores on process indicators of CVRM in CHD patients, but not on intermediate patient outcome measures. Direct support for patients and clinicians seemed most influential.
Two-dimensional strain profiles in patients with physiological and pathological hypertrophy and preserved left ventricular systolic function: a comparative analyses
Authors: Afonso Luis , Kondur Ashok , Simegn Mengistu , Niraj Ashutosh , Hari Pawan , Kaur Ramanjit , Ramappa Preeti , Pradhan Jyotiranjan , Bhandare Deepti , Williams Kim A , Zalawadiya Sandip , Pinheiro Aurelio , Abraham Theodore P 
Published: August 2012

ObjectiveThis study was designed to examine the utility of two-dimensional strain (2DS) or speckle tracking imaging to typify functional adaptations of the left ventricle in variant forms of left ventricular hypertrophy (LVH).DesignCross-sectional study.SettingUrban tertiary care academic medical centres.ParticipantsA total of 129 subjects, 56 with hypertrophic cardiomyopathy (HCM), 34 with hypertensive left ventricular hypertrophy (H-LVH), 27 professional athletes with LVH (AT-LVH) and 12 healthy controls in sinus rhythm with preserved left ventricular systolic function.MethodsConventional echocardiographic and tissue Doppler examinations were performed in all study subjects. Bi-dimensional acquisitions were analysed to map longitudinal systolic strain (automated function imaging, AFI, GE Healthcare, Waukesha, Wisconsin, USA) from apical views.ResultsSubjects with HCM had significantly lower regional and average global peak longitudinal systolic strain (GLS-avg) compared with controls and other forms of LVH. Strain dispersion index, a measure of regional contractile heterogeneity, was higher in HCM compared with the rest of the groups. On receiver operator characteristics analysis, GLS-avg had excellent discriminatory ability to distinguish HCM from H-LVH area under curve (AUC) (0.893, p<0.001) or AT-LVH AUC (0.920, p<0.001). Tissue Doppler and LV morphological parameters were better suited to differentiate the athlete heart from HCM.Conclusions2DS (AFI) allows rapid characterisation of regional and global systolic function and may have the potential to differentiate HCM from variant forms of LVH.
Impact of television coverage on the number and type of symptoms reported during a health scare: a retrospective pre–post observational study
Authors: Faasse Kate , Gamble Greg , Cundy Tim , Petrie Keith J 
Published: August 2012

ObjectivesThis study investigated the impact of television news coverage on total adverse event reporting rates 1 month before and after the bulletins during a medication health scare. We further investigated whether individual side effects mentioned in each bulletin were reflected in the adverse event reports following the coverage.DesignA retrospective pre–post observational study.SettingNew Zealand Centre for Adverse Reactions Monitoring.ParticipantsAdverse events reported from May to December 2008 relating to Eltroxin formulation change.Primary and secondary outcome measuresPrimary outcome measure was the total rate of adverse event reporting per day. Secondary outcome measure was the rate of reporting of seven individual symptoms mentioned in the television coverage.ResultsAfter story 1, a significant increase in total reporting rates was evident (MdnPre=0, MdnPost=13.5, U=2, p<0.001, r=−0.86) with larger effect sizes for increases in television-mentioned symptoms. Story 2 also showed a significant increase in total adverse event reporting (MdnPre=6, MdnPost=18.5, U=86.5, p=0.002, r=−0.49) driven by significant increases only in television-reported symptoms. Story 3 did not result in a significant increase in total reporting (MdnPre=12; MdnPost=15.5, U=171, p=0.432, r=−0.12), and showed a significant increase in reporting rates for only one of the two television-reported symptoms.ConclusionsThe findings suggest that television news coverage can impact on the overall rate of adverse event reporting during a health scare, in part via increased reporting of media-mentioned side effects. The effects of television media coverage on adverse event reporting appear strongest for earlier reports.
Attitudes to morphine in chronic heart failure patients
Authors: Oxberry Stephen G , Jones Lesley , Clark Andrew L , Johnson Miriam J 
Published: August 2012

Abstract

Objectives
Low-dose opioids are used for the palliation of pain, breathlessness and cough in advanced chronic heart failure (CHF) patients. The authors wanted to determine any potential barriers or facilitators to opioid administration in patients with CHF by assessing their knowledge, concerns and attitudes to morphine therapy.

Methods
Semistructured interviews were held with a purposive sample of 10 men with symptoms of CHF. Data were analysed using a constant comparative approach until thematic saturation.

Results
Four key areas emerged: medication use; symptoms; prior morphine experience; and attitudes, concerns and anxieties regarding morphine use. Despite polypharmacy, participants said that morphine would be acceptable if it was monitored by a trusted healthcare professional. Many patients had experienced morphine before, often in life-threatening situations such as myocardial infarction, when it had helped greatly. Opioids were not strongly associated exclusively with death and dying (in contrast to patient reports in the cancer literature).

Conclusions
Although some concerns about morphine were expressed, these did not appear to override a willingness to consider its use if recommended by a trusted clinician. However, some participants perceived that their doctor was concerned about its use, holding it as a last reserve. Morphine appears to be an acceptable breathlessness treatment option to these people with CHF. Prescribers may need education and reassurance if these medicines are to be used to their full potential and views may be different in other communities.
Republished: Development and evaluation of a 3-day patient safety curriculum to advance knowledge, self-efficacy and system thinking among medical students
Authors: Aboumatar Hanan J , Thompson David , Wu Albert , Dawson Patty , Colbert Jorie , Marsteller Jill , Kent Paula , Lubomski Lisa H , Paine Lori , Pronovost Peter 
Published: August 2012

Abstract

Purpose
To develop a patient safety curriculum and evaluate its impact on medical students' safety knowledge, self-efficacy and system thinking.

Methods
This study reports on curriculum development and evaluation of a 3-day, clinically oriented patient safety intersession that was implemented at the Johns Hopkins School of Medicine in January 2011. Using simulation, skills demonstrations, small group exercises and case studies, this intersession focuses on improving students' teamwork and communication skills and system-based thinking while teaching on the causes of preventable harm and evidence-based strategies for harm prevention. One hundred and twenty students participated in this intersession as part of their required second year curriculum. A pre–post assessment of students' safety knowledge, self-efficacy in safety skills and system-based thinking was conducted. Student satisfaction data were also collected.

Results
Students' safety knowledge scores significantly improved (mean +19% points; 95% CI 17.0 to 21.6; p&lt;0.01). Composite system thinking scores increased from a mean pre-intersession score of 60.1 to a post-intersession score of 67.6 (p&lt;0.01). Students had statistically significant increases in self-efficacy for all taught communication and safety skills. Participant satisfaction with the intersession was high.

Conclusions
The patient safety intersession resulted in increased knowledge, system-based thinking, and self-efficacy scores among students. Similar intersessions can be implemented at medical, nursing, pharmacy and other allied health schools separately or jointly as part of required school curricula. Further study of the long-term impact of such education on knowledge, skills, attitudes and behaviours of students is warranted.
Falling mortality rates in Type 2 diabetes mellitus in the Wirral Peninsula: a longitudinal and retrospective cohort population-based study
Authors: Nwaneri Chukwuemeka , Bowen-Jones David , Cooper Helen , Chikkaveerappa Krishnamurthy , Afolabi Banjo Adekunle 
Published: August 2012

Abstract

Objectives
To determine the life expectancy and mortality rates in patients with type 2 diabetes mellitus when compared with the UK general population; to measure the years of life lost.

Design
Longitudinal and retrospective cohort study.

Setting
The Wirral Peninsula in the northwest of England.

Participants
Total of 13 620 patients with type 2 diabetes mellitus on the Wirral Diabetes Register.

Main Outcome measure
All-cause mortality, from 1 January 2000 to 31 December 2007.

Results
Over the 8-year period of the study, there were a total of 16 692.5 person-years lived and 3888 deaths; 2041 (52.5%) males and 1847 (47.5%) females with corresponding mean ages at death of 75.6±10.3 years and 80.2±10.2 years, respectively. Although prevalence rates increased linearly (from 1.06% in 2000 to 4.39% in 2007) a decrease in mortality rates (from 117 to 46 per 1000 population) in both sexes was observed. This coincided with a progressive fall in cardiovascular risk factors in this population. A survival time curve of life lived until death showed that males had 8.0 years reduction in life span and females' life span was reduced by 9.6 years when compared with UK general population. In both sexes, life expectancy was reduced by between 2 and 11 years dependent on the age of diagnosis, with males showing a greater degree of reduction.

Conclusion
Type 2 diabetes mellitus is associated with a significant reduction in life expectancy, more markedly in men, and in those diagnosed before age 70 years. However, annual mortality rates have fallen progressively in our population and may contribute to longer survival and life expectancy in future years.
Chromosomal characterization in native populations of Elymus scabrifolius from Argentina through classical and molecular cytogenetics (FISH–GISH)
Authors: Tomas P.A. , González G.E. , Schrauf G.E. , Poggio L. 
Published: August 2012

The karyotype of Elymus scabrifolius (Döll) J.H. Hunz. (2n = 4x = 28) was investigated by DAPI staining and in situ hybridization. All the accessions studied presented a symmetric and uniform karyotype constituted by 9m+2m–sm+3sm. DAPI stain showed 1–7 conspicuous bands in all the chromosomes and polymorphisms between accessions. FISH experiments carried out with 45S rDNA as probe (pTa71) showed strong hybridization signals on the metacentric SAT-chromosome pair 8; the submetacentric SAT-chromosome pair 13 presented weaker hybridization. FISH using pSc119.2 clone as probe identified five chromosome pairs. Then, the combination of chromosome morphology, DAPI-staining, and FISH enabled the accurate identification of each chromosome pair in E. scabrifolius. Genomic in situ hybridization (GISH) experiments using Hordeum DNA as probe on mitotic metaphases confirmed unequivocally the presence of the H genome in E. scabrifolius, allowing us to observe six uniformly labeled chromosome pairs and two chromosome pairs with only one arm labeled. The remaining six chromosome pairs were weakly labeled. The rehybridization of FISH slides with Hordeum DNA as probe allow us to assign the genomic provenance of most of the chromosomes in the studied accessions. Moreover, intergenomic rearrangement was detected between genome H and the still unknown progenitor genome.
Magnetostratigraphy, fence diagrams and basin analysis
Authors: Yan Maodu , Van Der Voo Rob , Fang Xiao-Min , Song Chunhui 
Published: August 2012

Abstract
Correlation of lithostratigraphic sections is widely used to examine the nature of lateral facies changes within or between basins. It can provide significant clues for regional environmental and palaeogeographic reconstructions. There are problems associated with lithostratigraphic correlation; diachronous deposition of similar lithological units may not be recognized. We report here an attempt to determine lateral facies changes in coeval sedimentary sections, through three-dimensional magnetostratigraphic correlations in the Guide Basin, an intramontane basin in the northeastern part of the Tibetan Plateau. The method is successful for correlating lateral facies and helps to identify sediment sources in the basin.
Oligocene–Miocene magnetostratigraphy of deep-sea sediments from the equatorial Pacific (IODP Site U1333)
Authors: Guidry E. P. , Richter C. , Acton G. D. , Channell J. E. T. , Evans H. F. , Ohneiser C. , Yamamoto Y. , Yamazaki T. 
Published: August 2012

Abstract
We present palaeomagnetic results from the Oligocene through Miocene part of the Integrated Ocean Drilling Program Site U1333 (1030.996′N, 138°25.159′W), which is located in 4853 m-deep water over seafloor with an estimated crustal age of 46 Ma. Detailed magnetostratigraphic investigations are essential to provide a sound age model for the study of the palaeoclimatic and palaeo-oceanographic history of the Cenozoic of the Equatorial Pacific and to improve the database of Pacific magnetostratigraphy. Rock magnetic measurements were carried out at 1 cm resolution on 81 U-channel samples from the spliced section with the goal of extracting a high-resolution record of the magnetostratigraphy. Stepwise demagnetization of the natural remanent magnetization yielded a well-defined magnetostratigraphy over a time interval of approximately 10 Ma between the base of Chron C6n (19.722 Ma) and the middle of Chron C11r (>29.9 Ma) and identification of the Oligocene–Miocene transition at the base of Subchron C6Cn.2n. The palaeomagnetic data are characterized by shallow inclinations, and by 180° alternations in declinations downhole, reflecting magnetic polarity zones. The relatively high temporal resolution allowed for the identification of three possible excursions previously not identified on the geomagnetic polarity time scale, which were recorded in Subchrons C8n.1r and C11n.2n and in Chron C11r.
RAP80 Is Critical in Maintaining Genomic Stability and Suppressing Tumor Development
Authors: Yin Zhengyu , Menendez Daniel , Resnick Michael A. , French John E. , Janardhan Kyathanahalli S. , Jetten Anton M. 
Published: August 2012

Abstract
The ubiquitin interaction motif-containing protein RAP80 was recently found to play a key role in DNA damage response (DDR) signaling by facilitating the translocation of several DDR mediators, including BRCA1, to ionizing irradiation (IR)-induced foci. In this study, we examine the effect of the loss of RAP80 on genomic stability and the susceptibility to cancer development in RAP80 null (RAP80−/−) mice. RAP80−/− mice are viable and did not exhibit any apparent developmental defects. Mouse embryonic fibroblasts (MEF) derived from RAP80−/− mice underwent premature senescence compared with wild-type (WT) MEFs, were more sensitive to IR, and exhibited a higher level of spontaneous and IR-induced genomic instability. RAP80−/− thymocytes were more sensitive to IR-induced cell death than WT thymocytes. RAP80−/− mice were more susceptible to spontaneous lymphoma development and the development of 7,12-dimethylbenz(a)anthracene-induced mammary gland tumors. Moreover, the loss of RAP80 accelerated tumor formation in both p53−/− and p53+/− mice. Our data indicate that RAP80-deficiency promotes genomic instability and causes an increase in cancer risk consistent with the concept that RAP80 exhibits a tumor suppressor function. Cancer Res; 72(19); 5080–90. ©2012 AACR.
Src Inhibition with Saracatinib Reverses Fulvestrant Resistance in ER-Positive Ovarian Cancer Models In Vitro and In Vivo
Authors: Simpkins Fiona , Hevia-Paez Pedro , Sun Jun , Ullmer Wendy , Gilbert Candace A. , da Silva Thiago , Pedram Ali , Levin Ellis R. , Reis Isildinha M. , Rabinovich Brian , Azzam Diana , Xu Xiang-Xi , Ince Tan A. , Yang Ji-Yeon , Verhaak Roel G.W. , Lu Yiling , Mills Gordon B. , Slingerland Joyce M. 
Published: August 2012

Abstract
Purpose: More effective, less toxic treatments for recurrent ovarian cancer are needed. Although more than 60% of ovarian cancers express the estrogen receptor (ER), ER-targeted drugs have been disappointing due to drug resistance. In other estrogen-sensitive cancers, estrogen activates Src to phosphorylate p27 promoting its degradation and increasing cell-cycle progression. Because Src is activated in most ovarian cancers, we investigated whether combined Src and ER blockade by saracatinib and fulvestrant would circumvent antiestrogen resistance.
Experimental Design: ER and Src were assayed in 338 primary ovarian cancers. Dual ER and Src blockade effects on cell cycle, ER target gene expression, and survival were assayed in ERα+ ovarian cancer lines, a primary human ovarian cancer culture in vitro, and on xenograft growth.
Results: Most primary ovarian cancers express ER. Src activity was greater in ovarian cancer lines than normal epithelial lines. Estrogen activated Src, ER-Src binding, and ER translocation from cytoplasm to nucleus. Estrogen-mediated mitogenesis was via ERα, not ERβ. While each alone had little effect, combined saracatinib and fulvestrant increased p27 and inhibited cyclin E-Cdk2 and cell-cycle progression. Saracatinib also impaired induction of ER-target genes c-Myc and FOSL1; this was greatest with dual therapy. Combined therapy induced autophagy and more effectively inhibited ovarian cancer xenograft growth than monotherapy.
Conclusions: Saracatinib augments effects of fulvestrant by opposing estrogen-mediated Src activation and target gene expression, increasing cell-cycle arrest, and impairing survival, all of which would oppose antiestrogen resistance in these ER+ ovarian cancer models. These data support further preclinical and clinical evaluation of combined fulvestrant and saracatinib in ovarian cancer. Clin Cancer Res; 18(21); 5911–23. ©2012 AACR.
Intracerebral CpG Immunotherapy with Carbon Nanotubes Abrogates Growth of Subcutaneous Melanomas in Mice
Authors: Fan Haitao , Zhang Ian , Chen Xuebo , Zhang Leying , Wang Huaqing , Da Fonseca Anna , Manuel Edwin R. , Diamond Don J. , Raubitschek Andrew , Badie Behnam 
Published: August 2012

Abstract
Purpose: Recently, we showed that intratumoral delivery of low-dose, immunostimulatory CpG oligodeoxynucleotides conjugated with carbon nanotubes (CNT-CpG) was more effective than free CpG and not only eradicated intracranial (i.c.) gliomas but also induced antitumor immunity that protected mice from subsequent i.c. or systemic tumor rechallenge. Here, we examined whether the same “intracerebral immunotherapy” strategy could be applied to the treatment of metastatic brain tumors.
Experimental Design: Mice with both i.c. and s.c. melanomas were injected intratumorally with CNT-CpG into either location. Antitumor responses were assessed by flow cytometry, bioluminescent imaging, and animal survival.
Results: When given s.c., CNT-CpG response was mostly local, and it only modestly inhibited the growth of i.c. melanomas. However, i.c. CNT-CpG abrogated the growth of not only brain but also s.c. tumors. Furthermore, compared with s.c. injections, i.c. CNT-CpG elicited a stronger inflammatory response that resulted in more potent antitumor cytotoxicity and improved in vivo trafficking of effector cells into both i.c. and s.c. tumors. To investigate factors that accounted for these observations, CNT-CpG biodistribution and cellular inflammatory responses were examined in both tumor locations. Intracranial melanomas retained the CNT-CpG particles longer and were infiltrated by Toll-like receptor (TLR-9)–positive microglia. In contrast, myeloid-derived suppressive cells were more abundant in s.c. tumors. Although depletion of these cells before s.c. CNT-CpG therapy enhanced its cytotoxic responses, antitumor responses to brain melanomas were unchanged.
Conclusions: These findings suggest that intracerebral CNT-CpG immunotherapy is more effective than systemic therapy in generating antitumor responses that target both brain and systemic melanomas. Clin Cancer Res; 18(20); 5628–38. ©2012 AACR.
Molecular Pathways: The Complexity of the Epigenome in Cancer and Recent Clinical Advances
Authors: Conte Mariarosaria , Altucci Lucia 
Published: August 2012

Abstract
Human cancer is causally linked to genomic and epigenomic deregulations. Epigenetic abnormalities occurring within signaling pathways regulating proliferation, migration, growth, differentiation, transcription, and death signals may be critical in the progression of malignancies. Consequently, identification of epigenetic marks and their bioimplications in tumors represents a crucial step toward defining new therapeutic strategies both in cancer treatment and prevention. Alterations of writers, readers, and erasers in cancer may affect, for example, the methylation and acetylation state of huge areas of chromatin, suggesting that epi-based treatments may require “distinct” therapeutic strategies compared with “canonical” targeted treatments. Whereas anticancer treatments targeting histone deacetylase and DNA methylation have entered the clinic, additional chromatin modification enzymes have not yet been pharmacologically targeted for clinical use in patients. Thus, a greater insight into alterations occurring on chromatin modifiers and their impact in tumorigenesis represents a crucial advancement in exploiting epigenetic targeting in cancer prevention and treatment. Here, the interplay of the best known epi-mutations and how their targeting might be optimized are addressed. Clin Cancer Res; 18(20); 5526–34. ©2012 AACR.
Therapeutic Drug Monitoring of Imatinib—New Data Strengthen the Case
Authors: Judson Ian 
Published: August 2012

Abstract
A population pharmacokinetic study of imatinib in patients with gastrointestinal stromal tumor by Eechoute and colleagues has shown a significant increase in drug clearance over the first 3 months of treatment, resulting in a 30% decrease in drug exposure. This finding clearly shows the possibility of pharmacokinetic resistance in this disease. Clin Cancer Res; 18(20); 5517–9. ©2012 AACR.