bluuebunny/crossref_metadata_2025_split huggingface dataset:
Public perceptions of cancer: a qualitative study of the balance of positive and negative beliefs
Authors: Robb Kathryn A , Simon Alice E , Miles Anne , Wardle Jane 
Published: July 2014

ObjectivesCancer's insidious onset and potentially devastating outcomes have made it one of the most feared diseases of the 20th century. However, advances in early diagnosis and treatment mean that death rates are declining, and there are more than 30 million cancer survivors worldwide. This might be expected to result in more sanguine attitudes to the disease. The present study used a qualitative methodology to provide an in-depth exploration of attitudes to cancer and describes the balance of negative and positive perspectives.DesignA qualitative study using semistructured interviews with thematic analysis.SettingA university in London, UK.Participants30 participants (23–73 years), never themselves diagnosed with cancer.ResultsAccounts of cancer consistently incorporated negative and positive views. In almost all respondents, the first response identified fear, trauma or death. However, this was followed—sometimes within the same sentence—by acknowledgement that improvements in treatment mean that many patients can survive cancer and may even resume a normal life. Some respondents spontaneously reflected on the contradictions, describing their first response as a ‘gut feeling’ and the second as a more rational appraisal—albeit one they struggled to believe. Others switched perspective without apparent awareness.ConclusionsPeople appear to be ‘in two minds’ about cancer. A rapid, intuitive sense of dread and imminent death coexists with a deliberative, rational recognition that cancer can be a manageable, or even curable, disease. Recognising cancer's public image could help in the design of effective cancer control messages.
Parenting roles and knowledge in neonatal intensive care units: protocol of a mixed methods study
Authors: Alves Elisabete , Amorim Mariana , Fraga Sílvia , Barros Henrique , Silva Susana 
Published: July 2014

IntroductionThere is a strong focus on the translation of scientific knowledge into evidence-based practice when dealing with very preterm births. The aim is to standardise and rationalise healthcare. The incorporation of parents’ perspectives with respect to the organisation of care and technical interventions in neonatal intensive care units (NICUs) is needed. This study aims to analyse the repertoire of meanings, knowledge and emotions actualised by the parents of very preterm infants hospitalised in NICUs in the decision process regarding parental care, treatment options and uses of information sources.Methods and analysisThis is a mixed-methods, observational study. The methodological strategy will rely on: (1) Ethnographic observation, carried out in a level III NICU located in the North of Portugal, during 6 months; (2) NICU-based surveys of mothers and fathers of very preterm infants born between July 2013 and June 2014 and admitted at the seven public level III NICUs of the Northern Health Region of Portugal; (3) Single and couple semistructured interviews to a subsample of mothers and fathers of very preterm infants, 4 months after birth. Inferential statistics will be used to analyse the quantitative data and content analysis, with an iterative and reflexive process and will be implemented to assess qualitative data.Ethics and disseminationThe study protocol was approved by the National Data Protection Commission and the Ethics Committee of all the hospitals involved. The current project will contribute to develop resources for enriched good medical practices in the context of neonatal services through integrating insights from social sciences, public health, epidemiology and ethics. The expected dissemination actions are effective tools in designing strategies that aim to develop family-centred care and to improve medical practices in the context of neonatal services.
Herding Cats
Authors: Alglave Jade , Maranget Luc , Tautschnig Michael 
Published: July 2014

We propose an axiomatic generic framework for modelling weak memory. We show how to instantiate this framework for Sequential Consistency (SC), Total Store Order (TSO), C++ restricted to release-acquire atomics, and Power. For Power, we compare our model to a preceding operational model in which we found a flaw. To do so, we define an operational model that we show equivalent to our axiomatic model.
We also propose a model for ARM. Our testing on this architecture revealed a behaviour later acknowledged as a bug by ARM, and more recently, 31 additional anomalies.
We offer a new simulation tool, called herd, which allows the user to specify the model of his choice in a concise way. Given a specification of a model, the tool becomes a simulator for that model. The tool relies on an axiomatic description; this choice allows us to outperform all previous simulation tools. Additionally, we confirm that verification time is vastly improved, in the case of bounded model checking.
Finally, we put our models in perspective, in the light of empirical data obtained by analysing the C and C++ code of a Debian Linux distribution. We present our new analysis tool, called mole, which explores a piece of code to find the weak memory idioms that it uses.
Incidence of Colorectal Adenomas: Birth Cohort Analysis among 4.3 Million Participants of Screening Colonoscopy
Authors: Brenner Hermann , Altenhofen Lutz , Stock Christian , Hoffmeister Michael 
Published: July 2014

Abstract
Background: Most colorectal cancers develop from adenomas. We aimed to estimate sex- and age-specific incidence rates of colorectal adenomas and to assess their potential implications for colorectal cancer screening strategies.
Methods: Sex- and age-specific incidence rates of colorectal adenomas were derived by a birth cohort analysis using data from 4,322,085 screening colonoscopies conducted in Germany and recorded in a national database in 2003–2012. In addition, cumulative risks of colorectal cancer among colonoscopically neoplasm-free men and women were estimated by combining adenoma incidence rates with previously derived adenoma-colorectal cancer transition rates.
Results: Estimated annual incidence in percentage (95% confidence interval) in age groups 55–59, 60–64, 65–69, 70–74, and 75–79 was 2.4 (2.2–2.6), 2.3 (2.1–2.6), 2.4 (2.1–2.6), 2.2 (1.8–2.5), and 1.8 (1.2–2.3) among men, and 1.4 (1.3–1.5), 1.5 (1.4–1.7), 1.6 (1.4–1.8), 1.6 (1.3–1.8), and 1.2 (0.8–1.6) among women. Estimated 10- and 15-year risks of clinically manifest colorectal cancer were 0.1% and 0.5% or lower, respectively, in all groups assessed.
Conclusions: Annual incidence rates of colorectal adenomas are below 2.5% and 2% among men and women, respectively, and show little variation by age.
Impact: Risk of clinically manifest colorectal cancer is expected to be very small within 10 years and beyond after negative colonoscopy for men and women at all ages. The use of rescreening after a negative screening colonoscopy above 60 years of age may be very limited. Cancer Epidemiol Biomarkers Prev; 23(9); 1920–7. ©2014 AACR.
Phase I Safety and Pharmacodynamic of Inecalcitol, a Novel VDR Agonist with Docetaxel in Metastatic Castration-Resistant Prostate Cancer Patients
Authors: Medioni Jacques , Deplanque Gael , Ferrero Jean-Marc , Maurina Tristan , Rodier Jean-Michel P. , Raymond Eric , Allyon Jorge , Maruani Gerard , Houillier Pascal , Mackenzie Sarah , Renaux Stephanie , Dufour-Lamartinie Jean-Francois , Elaidi Reza , Lerest Celine , Oudard Stephane 
Published: July 2014

Abstract
Purpose: We conducted a phase I multicenter trial in naïve metastatic castrate-resistant prostate cancer patients with escalating inecalcitol dosages, combined with docetaxel-based chemotherapy. Inecalcitol is a novel vitamin D receptor agonist with higher antiproliferative effects and a 100-fold lower hypercalcemic activity than calcitriol.
Experimental Design: Safety and efficacy were evaluated in groups of three to six patients receiving inecalcitol during a 21-day cycle in combination with docetaxel (75 mg/m2 every 3 weeks) and oral prednisone (5 mg twice a day) up to six cycles. Primary endpoint was dose-limiting toxicity (DLT) defined as grade 3 hypercalcemia within the first cycle. Efficacy endpoint was ≥30% PSA decline within 3 months.
Results: Eight dose levels (40–8,000 μg) were evaluated in 54 patients. DLT occurred in two of four patients receiving 8,000 μg/day after one and two weeks of inecalcitol. Calcemia normalized a few days after interruption of inecalcitol. Two other patients reached grade 2, and the dose level was reduced to 4,000 μg. After dose reduction, calcemia remained within normal range and grade 1 hypercalcemia. The maximum tolerated dose was 4,000 μg daily. Respectively, 85% and 76% of the patients had ≥30% PSA decline within 3 months and ≥50% PSA decline at any time during the study. Median time to PSA progression was 169 days.
Conclusion: High antiproliferative daily inecalcitol dose has been safely used in combination with docetaxel and shows encouraging PSA response (≥30% PSA response: 85%; ≥50% PSA response: 76%). A randomized phase II study is planned. Clin Cancer Res; 20(17); 4471–7. ©2014 AACR.
Chronic Treatment With Ticagrelor Limits Myocardial Infarct Size
Authors: Nanhwan Manjyot K. , Ling Shukuan , Kodakandla Monica , Nylander Sven , Ye Yumei , Birnbaum Yochai 
Published: July 2014

Objective—

In a phase III clinical trial (PLATelet inhibition and patient Outcomes, PLATO), ticagrelor provided better clinical outcomes than clopidogrel in patients with acute coronary syndromes. In addition to P2Y
12
-receptor antagonism, ticagrelor prevents cell uptake of adenosine and has proven able to augment adenosine effects. Adenosine protects the heart against ischemia–reperfusion injury. We compared the effects of clopidogrel and ticagrelor on myocardial infarct size (IS).

Approach and Results—

Rats received oral ticagrelor (0, 75, 150, or 300 mg/kg/d) or clopidogrel (30 or 90 mg/kg/d) for 7 days and underwent 30-minute coronary artery ligation and 24-hour reperfusion. Area at risk was assessed by blue dye and IS by 2,3,5-triphenyl-tetrazolium-chloride. Cyclooxygenase-2 (COX2) enzyme activity was assessed by ELISA and expression by real-time polymerase chain reaction. Mechanism responsible was explored using adenosine-receptor antagonist (CGS15943, an A
2A
/A
1
antagonist) or cyclooxygenase inhibition by either aspirin (5, 10, or 25 mg/kg) or specific cyclooxygenase-1 (SC560) or COX2 (SC5815) inhibitors. Ticagrelor, dose-dependently, reduced IS, whereas clopidogrel had no effect. Adenosine-receptor antagonism blocked the ticagrelor effect and COX2 inhibition by SC5815, or high-dose aspirin attenuated the IS-limiting effect of ticagrelor, whereas cyclooxygenase-1 inhibition or low-dose aspirin had no effect. Ticagrelor, but not clopidogrel, upregulated COX2 expression and activity. Also this effect was blocked by adenosine-receptor antagonism. Ticagrelor, but not clopidogrel, increased Akt and endothelial nitric oxide synthase phosphorylation.

Conclusions—
Ticagrelor, but not clopidogrel, reduces myocardial IS. The protective effect of ticagrelor was dependent on adenosine-receptor activation with downstream upregulation of endothelial nitric oxide synthase and COX2 activity.
Suppressor of Cytokine Signaling 1–Derived Peptide Inhibits Janus Kinase/Signal Transducers and Activators of Transcription Pathway and Improves Inflammation and Atherosclerosis in Diabetic Mice
Authors: Recio Carlota , Oguiza Ainhoa , Lazaro Iolanda , Mallavia Beñat , Egido Jesus , Gomez-Guerrero Carmen 
Published: July 2014

Objective—
Activation of Janus kinase/signal transducers and activators of transcription (STAT) pathway by hyperglycemia and dislypidemia contributes to the progression of diabetic complications, including atherosclerosis. Suppressor of cytokine signaling (SOCS) proteins negatively regulate Janus kinase/STAT and have emerged as promising target for anti-inflammatory therapies. We investigated whether a cell-permeable lipopeptide corresponding to the kinase inhibitory region of SOCS1 could reduce atherosclerosis in diabetic mice and identified the mechanisms involved.

Approach and Results—

Streptozotocin-induced diabetic apolipoprotein E–deficient mice (aged 8 and 22 weeks) were given intraperitoneal injections of vehicle, SOCS1-derived peptide, or control mutant peptide for 6 to 10 weeks. SOCS1 therapy suppressed STAT1/STAT3 activation in atherosclerotic plaques of diabetic mice and significantly reduced lesion size at both early and advanced stages of lesion development compared with vehicle group. Plaque characterization demonstrated that SOCS1 peptide decreased the accumulation of lipids, macrophages, and T lymphocytes, whereas increasing collagen and smooth muscle cell content. This atheroprotective effect was accompanied by systemic (reduced proinflammatory Ly6C
high
monocytes and splenic cytokine expression) and local (reduced aortic expression of chemokines and cytokines) mechanisms, without impact on metabolic parameters. In vitro, SOCS1 peptide dose dependently inhibited STAT1/STAT3 activation and target gene expression in vascular smooth muscle cells and macrophages and also suppressed cytokine-induced cell migration and adhesion processes.

Conclusions—
SOCS1-based targeting Janus kinase/STAT restrains key mechanisms of atherogenesis in diabetic mice, thereby preventing plaque formation and increasing plaque stability. Approaches to mimic native SOCS1 functions may have a therapeutic potential to retard the progression of diabetic complications.
Reduction in Overall Occurrences of Ischemic Events With Vorapaxar: Results From TRACER
Authors: White Harvey D. , Huang Zhen , Tricoci Pierluigi , Van de Werf Frans , Wallentin Lars , Lokhnygina Yuliya , Moliterno David J. , Aylward Philip E. , Mahaffey Kenneth W. , Armstrong Paul W. 
Published: July 2014

Background

Clinical trials traditionally use time‐to‐first‐event analysis embedded within the composite endpoint of cardiovascular death (
CVD
), myocardial infarction (
MI
), or stroke. However, many patients have >1 event, and this approach may not reflect overall experience. We addressed this by analyzing all cardiovascular events in TRACER.

Methods and Results

TRACER randomized 12 944 patients with non‐
ST
‐segment elevation acute coronary syndromes to placebo or to protease‐activated receptor 1 antagonist vorapaxar with a median follow‐up of 502 days (interquartile range, 349 to 667). Analysis of vorapaxar's effect on recurrent
CVD
,
MI
, or stroke was prespecified using the Wei, Lin, and Weissfeld approach. Vorapaxar did not reduce the first occurrence of the primary endpoint of
CVD
,
MI
, stroke, revascularization, or rehospitalization for recurrent ischemia, but reduced the secondary composite endpoint of
CVD
,
MI
, or stroke (14.7% vorapaxar vs. 16.4% placebo; hazard ratio [
HR],
0.89; 95% confidence interval [
CI],
0.81 to 0.98;
P
=0.02; number needed to treat [
NNT
], 81). Recurrent secondary events occurred in 2.7% of patients. Vorapaxar reduced overall occurrences of ischemic events, first and subsequent (
HR,
0.88; 95%
CI,
0.80 to 0.98;
P
=0.02;
NNT,
51). Also, there was a trend indicating that vorapaxar reduced the expanded endpoint, including revascularization and rehospitalization for recurrent ischemia (
HR,
0.92; 95%
CI,
0.84 to 1.01;
P
=0.09). Vorapaxar increased overall occurrences of moderate and severe Global Use of Strategies to Open Occluded Coronary Arteries bleeding (
HR,
1.42; 95%
CI,
1.21 to 1.66;
P
<0.001) and Thrombolysis in Myocardial Infarction clinically significant bleeding (
HR,
1.550; 95%
CI,
1.403 to 1.713;
P
<0.001).

Conclusions
Vorapaxar reduced overall occurrences of ischemic events, but increased bleeding. These exploratory findings broaden our understanding of vorapaxar's potential and expand our understanding of the value of capturing recurrent events.

Clinical Trial Registration
URL: ClinicalTrials.gov. Unique identifier: NCT00527943.
Standard-Dose Intravenous Tissue-Type Plasminogen Activator for Stroke Is Better Than Low Doses
Authors: Liao Xiaoling , Wang Yilong , Pan Yuesong , Wang Chunjuan , Zhao Xingquan , Wang David Z. , Wang Chunxue , Liu Liping , Wang Yongjun 
Published: July 2014

Background and Purpose—
It remains uncertain whether lower dose intravenous tissue-type plasminogen activator (tPA) for stroke is as effective and safe as the standard dose.

Methods—
We analyzed data from the Thrombolysis Implementation and Monitor of Acute Ischemic Stroke in China (TIMS-China). Patients who were treated within 4.5 hours after symptom onset were included. These patients were divided into 5 groups according to tPA doses given: <0.5, 0.5 to 0.7, 0.7 to 0.85, 0.85 to 0.95, and ≥0.95 mg/kg. Symptomatic intracranial hemorrhage, mortality, and 90-day outcome assessed by modified Rankin scale were analyzed.

Results—

A total of 919 patients were enrolled. Among them, 9 had <0.5 mg/kg, 75 had 0.5 to 0.7 mg/kg, 131 had 0.7 to 0.85 mg/kg, 678 had 0.85 to 0.95 mg/kg, and 26 had ≥0.95 mg/kg. Because of sample sizes, only 0.5 to 0.7, 0.7 to 0.85, and 0.85 to 0.95 mg/kg groups were compared. Median tPA doses were 0.64, 0.79, and 0.90 mg, respectively. After adjustment for the baseline variables, there were no significant differences in mortality(5.41% versus 8.66% versus 7.36%;
P
=0.695) and symptomatic intracranial hemorrhage (0% versus 3.82% versus 1.46%;
P
=0.106). The 0.5 to 0.7 mg/kg group had less excellent recovery outcome (modified Rankin scale, 0–1) than 0.85 to 0.95 mg/kg group (41.89% versus 53.83%; odds ratio=0.58;
P
=0.031) at 90 days. The 0.70 to 0.85 mg/kg group had less functional independence outcome (modified Rankin scale, 0–2) than 0.85 to 0.95 mg/kg group (54.33% versus 64.51%; odds ratio=0.66;
P
=0.036) at 90 days.

Conclusions—
Our study suggests that standard-dose intravenous tPA for stroke had more favorable outcome without increasing the risk of symptomatic intracranial hemorrhage than low-dose tPA. For Asian people, 0.9 mg/kg should be the optimal dose of tPA to treat acute ischemic stroke.
Ischemic Postconditioning Relieves Cerebral Ischemia and Reperfusion Injury Through Activating T-LAK Cell–Originated Protein Kinase/Protein Kinase B Pathway in Rats
Authors: Zhao Haiping , Wang Rongliang , Tao Zhen , Gao Li , Yan Feng , Gao Zhi , Liu Xiangrong , Ji Xunming , Luo Yumin 
Published: July 2014

Background and Purpose—
Ischemic postconditioning (IPostC) protects against ischemic brain injury. To date, no study has examined the role of T-LAK-cell–originated protein kinase (TOPK) in IPostC-afforded neuroprotection. We explored the molecular mechanism related with TOPK in antioxidant effect of IPostC against ischemia/reperfusion.

Methods—
Focal ischemia was induced in rats by transient middle cerebral artery occlusion. Reactive oxygen species production in the peri-infarct cortex was detected using dihydroethidium. Malondialdehyde, as a marker of lipid peroxidation, and 3-nitrotyrosine, as a marker of protein oxidation, were detected by ELISA. The expression or location of antioxidant proteins and signal molecules TOPK, phosphatase, and tensin homolog, and Akt was analyzed by Western blotting and immunofluorescence.

Results—
Our results revealed that IPostC relieved transient middle cerebral artery occlusion–induced oxidative damage by reducing reactive oxygen species, malondialdehyde, and 3-nitrotyrosine accumulation in the peri-infarct cortex and raised levels of antioxidants perioxiredoxin-1, peroxiredoxin-2, and thioredoxin-1. In addition, IPostC increased p-AKT and p-TOPK levels, which colocalized in neural cells. In vitro TOPK knockdown by small interfering RNA decreased the levels of antioxidants peroxiredoxin-1, thioredoxin, and manganese superoxide dismutase activity in PC12 cells. In vivo intracerebroventricular injection of TOPK small interfering RNA reversed IPostC-induced neuroprotection by increasing infarct volume and nitric oxide content and reducing manganese superoxide dismutase activity. Moreover, IPostC-evoked Akt activation was blocked by TOPK small interfering RNA in vivo, but the decreased phosphorylated phosphatase and tensin homolog level in ischemia/reperfusion was not influenced by IPostC or by TOPK small interfering RNA treatment.

Conclusions—
Our results suggest that the antioxidative effects of TOPK/Akt might contribute to the neuroprotection of IPostC treatment against transient middle cerebral artery occlusion.
Sensitivity of Crop Water Need to 2071–95 Projected Temperature and Precipitation Changes in Jamaica
Authors: Curtis Scott , Gamble Douglas W. , Popke Jeff 
Published: July 2014

Abstract
This study uses empirical models to examine the potential impact of climate change, based on a range of 100-yr phase 5 of the Coupled Model Intercomparison Project (CMIP5) projections, on crop water need in Jamaica. As expected, crop water need increases with rising temperature and decreasing precipitation, especially in May–July. Comparing the temperature and precipitation impacts on crop water need indicates that the 25th percentile of CMIP5 temperature change (moderate warming) yields a larger crop water deficit than the 75th percentile of CMIP5 precipitation change (wet winter and dry summer), but the 25th percentile of CMIP5 precipitation change (substantial drying) dominates the 75th percentile of CMIP5 temperature change (extreme warming). Over the annual cycle, the warming contributes to larger crop water deficits from November to April, while the drying has a greater influence from May to October. All experiments decrease crop suitability, with the largest impact from March to August.
The ‘Malawi device’: a durable, reusable, low cost device from own materials for emergency ventilation during percutaneous tracheostomy
Authors: Pollach Gregor , Namboya Felix , Jung Kai 
Published: July 2014

The use of a tracheostomy is routine in current intensive care practice to facilitate weaning patients requiring prolonged respiratory support from mechanical ventilation. Percutaneous tracheostomy has become an established technique with an acceptable risk profile in appropriately selected patients, and has the advantage that it can be performed at the bedside without the need for an operating theatre. This is particularly relevant in a resource-poor setting. Ideally, percutaneous tracheostomy requires the presence of two skilled persons; one to perform the tracheostomy while the other controls the airway and withdraws the endo-tracheal tube at the appropriate time. This is not always possible in a resource poor setting with limited manpower. Without two operators, it is possible for the tracheal tube to become displaced before the completion of the tracheostomy with potentially disastrous consequences. We describe a method by which the airway and ventilation can be maintained if accidental tracheal extubation occurs before completion of a percutaneous tracheostomy. The ‘Malawi Device’, a cheap and simple modification of readily available equipment, enables a single operator to maintain the airway and ventilate the patient when the above scenario occurs.