bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comparison of actual versus predicted emergency ambulance journey times using generic Geographic Information System software
Authors: McMeekin Peter , Gray Jo , Ford Gary A , Duckett Jay , Price Christopher I 
Published: June 2013

Study objectiveThe planning of regional emergency medical services is aided by accurate prediction of urgent ambulance journey times, but it is unclear whether it is appropriate to use Geographical Information System (GIS) products designed for general traffic. We examined the accuracy of a commercially available generic GIS package when predicting emergency ambulance journey times under different population and temporal conditions.MethodsWe undertook a retrospective cohort study of emergency ambulance admissions to three emergency departments (ED) serving differing population distributions in northeast England (urban/suburban/rural). The transport time from scene to ED for all the highest priority dispatches between 1 October 2009 and 30 September 2010 was compared with predictions made by generic GIS software.ResultsFor 10 156 emergency ambulance journeys, the mean prediction discrepancy between actual and predicted journey times across all EDs was an underprediction of 1.6 min (SD 4.9). Underprediction was statistically significant at all population densities, but unlikely to be of clinical significance. Ambulances in urban areas were able to exceed general traffic speed, whereas, the opposite effect was seen in suburban and rural road networks. There were minor effects due to travel outside the busiest traffic times (mean overprediction 0.8 min) and during winter months (mean underprediction 0.4 min).ConclusionsIt is reasonable to estimate emergency ambulance journey times using generic GIS software, but in order to avoid insufficient regional ambulance provision it would be necessary to make small adjustments because of the tendency towards systematic underprediction.
A novel method for determining the difficulty of colonoscopic polypectomy
Authors: Gupta S , Miskovic D , Bhandari P , Dolwani S , McKaig B , Pullan R , Rembacken B , Riley S , Rutter M D , Suzuki N , Tsiamoulos Z , Valori R , Vance M E , Faiz O D , Saunders B P , Thomas-Gibson S 
Published: June 2013

IntroductionEndoscopists are now expected to perform polypectomy routinely. Colonic polypectomy varies in difficulty, depending on polyp morphology, size, location and access. The measurement of the degree of difficulty of polypectomy, based on polyp characteristics, has not previously been described.ObjectiveTo define the level of difficulty of polypectomy.MethodsConsensus by nine endoscopists regarding parameters that determine the complexity of a polyp was achieved through the Delphi method. The endoscopists then assigned a polyp complexity level to each possible combination of parameters. A scoring system to measure the difficulty level of a polyp was developed and validated by two different expert endoscopists.ResultsThrough two Delphi rounds, four factors for determining the complexity of a polypectomy were identified: size (S), morphology (M), site (S) and access (A). A scoring system was established, based on size (1–9 points), morphology (1–3 points), site (1–2 points) and access (1–3 points). Four polyp levels (with increasing level of complexity) were identified based on the range of scores obtained: level I (4–5), level II (6–9), level III (10–12) and level IV (>12). There was a high degree of interrater reliability for the polyp scores (interclass correlation coefficient of 0.93) and levels (κ=0.888).ConclusionsThe scoring system is feasible and reliable. Defining polyp complexity levels may be useful for planning training, competency assessment and certification in colonoscopic polypectomy. This may allow for more efficient service delivery and referral pathways.
Somatic Profiling of the Epidermal Growth Factor Receptor Pathway in Tumors from Patients with Advanced Colorectal Cancer Treated with Chemotherapy ± Cetuximab
Authors: Smith Christopher G. , Fisher David , Claes Bart , Maughan Timothy S. , Idziaszczyk Shelley , Peuteman Gilian , Harris Rebecca , James Michelle D. , Meade Angela , Jasani Bharat , Adams Richard A. , Kenny Sarah , Kaplan Richard , Lambrechts Diether , Cheadle Jeremy P. 
Published: June 2013

Abstract
Purpose: To study the somatic molecular profile of the EGF receptor (EGFR) pathway in advanced colorectal cancer, its relationship to prognosis, the site of the primary and metastases, and response to cetuximab.
Experimental Design: We used Sequenom and Pyrosequencing for high-throughput somatic profiling of the EGFR pathway in 1,976 tumors from patients with advanced colorectal cancer from the COIN trial (oxaliplatin and fluoropyrimidine chemotherapy ± cetuximab). Correlations between mutations, clinicopathologic, response, and survival data were carried out.
Results: Sequenom and Pyrosequencing had 99.0% (9,961/10,063) genotype concordance. We identified 13 different KRAS mutations in 42.3% of advanced colorectal cancers, 2 BRAF mutations in 9.0%, 4 NRAS mutations in 3.6%, and 5 PIK3CA mutations in 12.7%. 4.2% of advanced colorectal cancers had microsatellite instability (MSI). KRAS and PIK3CA exon 9, but not exon 20, mutations cooccurred (P = 8.9 × 10−4) as did MSI and BRAF mutations (P = 5.3 × 10−10). KRAS mutations were associated with right colon cancers (P = 5.2 × 10−5) and BRAF mutations with right (P = 7.2 × 10−5) and transverse colon (P = 9.8 × 10−6) cancers. KRAS mutations were associated with lung-only metastases (P = 2.3 × 10−4), BRAF mutations with peritoneal (P = 9.2 × 10−4) and nodal-only (P = 3.7 × 10−5) metastases, and MSI (BRAFWT) with nodal-only metastases (P = 2.9 × 10−4). MSI (BRAFWT) was associated with worse survival (HR = 1.89, 95% CI 1.30–2.76, P = 8.5 × 10−4). No mutations, subsets of mutations, or MSI status were associated with response to cetuximab.
Conclusions: Our data support a functional cooperation between KRAS and PIK3CA in colorectal tumorigenesis and link somatic profiles to the sites of metastases. MSI was associated with poor prognosis in advanced disease, and no individual somatic profile was associated with response to cetuximab in COIN. Clin Cancer Res; 19(15); 4104–13. ©2013 AACR.
Is Conflict of Interest Becoming a Challenge for Institution-Based Institutional Review Boards?
Authors: Freedman Ralph S. , McKinney Ross 
Published: June 2013

Abstract
Expansion of business relationships between academic institutions and their leaders and industry have become a reality, whereas media attention regarding conflict of interest (COI) at academic institutions has raised concerns about possible erosion of public trust. The Institutional Review Board (IRB) should collaborate with institutional COI committees to ensure that research with human subjects is in compliance with various applicable federal regulations. The IRB and COI committee should take additional independent action as necessary under their separate mandates to protect the welfare, safety, and rights of human subjects and to include limits on protocols affected by significant financial interests of the institution or its decision makers. If unable to review research due to an intrainstitutional conflict, the local IRB should consider transferring the study review and oversight to an external unaffiliated institutional or central IRB. A process for involvement of an executive institutional IRB is proposed. Clin Cancer Res; 19(15); 4034–9. ©2013 AACR.
Epithelial-Specific Deletion of 11β-HSD2 Hinders Apcmin/+ Mouse Tumorigenesis
Authors: Jiang Li , Yang Shilin , Yin Huiyong , Fan Xiaofeng , Wang Suwan , Yao Bing , Pozzi Ambra , Chen Xiaoping , Harris Raymond C. , Zhang Ming-Zhi 
Published: June 2013

Abstract
Cyclooxygenase-2 (COX-2)–derived prostaglandin E2 (PGE2) promotes colorectal tumorigenesis. Glucocorticoids are endogenous and potent COX-2 inhibitors, and their local actions are downregulated by 11β-hydroxysteroid dehydrogenase type II (11β-HSD2)-mediated metabolism. Previously, it was reported that 11β-HSD2 is increased in human colonic and Apcmin/+ mouse intestinal adenomas and correlated with increased COX-2, and 11β-HSD2 inhibition suppressed the COX-2 pathway and decreased tumorigenesis. Because 11β-HSD2 is expressed in Apcmin/+ mouse intestinal adenoma stromal and epithelial cells, Apcmin/+ mice were generated with selective deletion of 11β-HSD2 in intestinal epithelial cells (Vil-Cre-HSD2−/− Apcmin/+). Deletion of 11β-HSD2 in intestinal epithelia led to marked inhibition of Apcmin/+ mouse intestinal tumorigenesis. Immunostaining indicated decreased 11β-HSD2 and COX-2 expression in adenoma epithelia, whereas stromal COX-2 expression was intact in Vil-Cre-HSD2−/− Apcmin/+ mice. In Vil-Cre-HSD2−/− Apcmin/+ mouse intestinal adenomas, both p53 and p21 mRNA and protein were increased, with a concomitant decrease in pRb, indicating glucocorticoid-mediated G1-arrest. Further study revealed that REDD1 (regulated in development and DNA damage responses 1), a novel stress-induced gene that inhibits mTOR signaling, was increased, whereas the mTOR signaling pathway was inhibited. Therefore, in Vil-Cre-HSD2−/− Apcmin/+ mice, epithelial cell 11β-HSD2 deficiency leads to inhibition of adenoma initiation and growth by attenuation of COX-2 expression, increased cell-cycle arrest, and inhibition of mTOR signaling as a result of increased tumor intracellular active glucocorticoids.
Implications:Inhibition of 11β-HSD2 may represent a novel approach for colorectal cancer chemoprevention by increasing tumor glucocorticoid activity, which in turn inhibits tumor growth by multiple pathways. Mol Cancer Res; 11(9); 1040–50. ©2013 AACR.
A novel fibrinogen B beta chain frameshift mutation causes congenital afibrinogenaemia
Authors: Yu Ziqiang , Cao Lijuan , Zhang Wei , Bai Xia , Ruan Changgeng , Zhang Jian , Zhao Xiaojuan , Wang Zhaoyue 
Published: June 2013

SummaryCongenital afibrinogenaemia is a rare autosomal recessive disorder caused by various mutations within the fibrinogen genes FGA, FGB and FGG. Ins/del mutations in FGB are extremely rare. We report a patient with afibrinogenaemia who suffered from umbilical cord bleeding and repeated bleeding episodes. His plasma fibrinogen levels could not be detected using the Clauss method and immunological methods. Molecular analyses revealed homozygosity in a novel four bases insertion in codon 40 of FGB exon 2 (g. 2833_2834 ins GTTT), which resulted in a truncated 50-residue polypeptide that contained 11 exceptional abnormal residues. In the transient expression experiments, mutant fibrinogen could be detected at higher level than wild-type fibrinogen in COS-7 cell lysates but not in culture media. These results suggest that the homozygous mutation in FGB could be responsible for congenital afibrinogenaemia in this patient. This frameshift mutation could impair fibrinogen assembly and secretion without influencing the protein synthesis.
Lipid-lowering therapy with statins reduces microparticle shedding from endothelium, platelets and inflammatory cells
Authors: Suades Rosa , Padró Teresa , Alonso Rodrigo , Mata Pedro , Badimon Lina 
Published: June 2013

SummaryHyperlipidaemia is a causal factor in the ethiopathogenesis of atherosclerosis. Statins are the cornerstone drug therapy for LDL-cholesterol (LDL-c) lowering, that exert beneficial effects beyond lipid lowering. Circulating microparticles (cMPs), microvesicles released by activated cells into the bloodstream, are markers of vascular and inflammatory cell activation with tentative role in disease progression. However, the role of statins on cMPs seems controversial. We aimed at the evaluation of the effects of lipid-lowering treatment (LLT) on cMP generation in patients in primary prevention of atherosclerosis. A case-control study was conducted in hypercholesterolaemic patients receiving LLT with statins and normocholesterolaemic controls (LLT+ and LLT−, respectively, n=37/group), matched by age, gender and LDL-c levels. cMPs were characterised by flow cytometry using annexin-V and cellspecific antibodies. In LLT+-patients overall numbers of cMPs (p<0.005) were lower than in controls. Levels of cMPs carrying parental cell markers from vascular and circulating cell origin (platelet, endothelial cell, pan-leukocyte and specific-leukocyte subsets) were significantly lower in blood of LLT+ compared to LLT−-patients. Moreover, MPs from LLT+-patients had reduced markers of activated platelets (αIIbβ3-integrin), activated inflammatory cells (αM-integrin) and tissue factor. The effect of LLT on cMP shedding was found to be accumulative in years. cMP shedding associated to cardiovascular risk in LLT+-patients. In summary, at similar plasma cholesterol levels patients on statin treatment had a significant lower number of cMPs carrying markers of activated cells. These findings indicate that statins protect against vascular cell activation.
Two Chromosome 9p21 Haplotype Blocks Distinguish Between Coronary Artery Disease and Myocardial Infarction Risk
Authors: Fan Meng , Dandona Sonny , McPherson Ruth , Allayee Hooman , Hazen Stanley L. , Wells George A. , Roberts Robert , Stewart Alexandre F.R. 
Published: June 2013

Background—
Variants at the 9p21 locus associate with the risk of coronary artery disease (CAD) or myocardial infarction (MI). However, atherosclerotic plaque deposition is distinct from MI (plaque rupture and thrombosis), and recent studies showed no association between these variants and MI in patients with preexisting CAD. We performed haplotype analysis at the 9p21 locus to test whether haplotypes at distinct linkage disequilibrium blocks predict these phenotypes.

Methods and Results—

Using 24 single-nucleotide polymorphisms genotyped in white patients without diabetes mellitus, we reconstructed haplotypes at the 9p21 locus. Patients with angiograhic CAD/MI had ≥1 epicardial stenosis >50% (n=2352), whereas controls were asymptomatic and over the age of 60 years (n=2116). For CAD patients, regression models examined the association of haplotypes with initial age of symptomatic CAD, number of diseased vessels, and history of MI. In the case-control study, only haplotypes at 1 block tagged by rs1333049 associated with CAD more so than MI. These haplotypes also associated with early onset of CAD (β=−0.13;
P
=1.37×10
–4
) and disease severity (β=0.1823;
P
=0.006) but not with prevalent MI among patients with CAD. In contrast, haplotypes at another block tagged by rs518394 associated with prevalent MI (β=0.239;
P
=2.05×10
–4
), but remarkably these are inversely associated with disease severity (β=−0.196;
P
=0.003). This MI association was replicated in the Cleveland Clinic GeneBank premature CAD cohort (n=1385; β=0.207;
P
=0.019).

Conclusions—
Variants/haplotypes at 2 blocks are distinguished at 9p21; those at 1 block predispose to atherosclerosis, whereas those at the other predispose to MI among patients with preexisting CAD.
Twenty-Year Analysis of Trends in the Incidence and In-Hospital Mortality for Lower-Extremity Arterial Thromboembolism
Authors: Korabathina Ravikiran , Weintraub Andrew R. , Price Lori Lyn , Kapur Navin K. , Kimmelstiel Carey D. , Iafrati Mark D. , Ali Tahir Syed M. 
Published: June 2013

Background—
Epidemiology data for lower-extremity arterial thromboembolism (LET) are limited and may result from either acute limb ischemia or an acute exacerbation of critical limb ischemia. Given marked changes in both diagnosis and therapy over the last 2 decades, we hypothesized that this time period would have witnessed reductions in both the incidence and in-hospital mortality of LET.

Methods and Results—

Data from 1988 through 2007 from the National Hospital Discharge Survey were analyzed. All admissions for patients with LET were extracted, and the respective
International Classification of Diseases, Ninth Revision, Clinical Modification
codes were internally validated for both LET and acute limb ischemia. Descriptive statistics were used. The validity of the codes was good for identifying LET cases but poor for identifying acute limb ischemia cases because many of these acute presentations were attributable to critical limb ischemia. Over the 20-year span, there were 1.76 million cases of LET. The incidence of LET decreased significantly from 42.4 per 100 000 persons between 1988 and 1997 to 23.3 per 100 000 persons between 1998 and 2007. The in-hospital mortality for LET decreased significantly from 8.28% between 1988 and 1997 to 6.34% between 1998 and 2007, and male patients achieved greater mortality reduction compared with female patients. Treatments for acute limb ischemia showed decreasing use of surgical bypass and amputation and increasing rates of catheter-based thrombolysis.

Conclusions—
Over the 20-year study period, there have been significant reductions in both LET incidence and in-hospital mortality. Unfortunately, LET admissions extracted from an administrative database comprise a diverse group of individuals, including those with acute and chronic forms of limb ischemia and iatrogenic arterial injury, limiting the true assessment of ALI incidence.
Determinants of high rates of smoking among people with psychosis living in a socially disadvantaged region in South Australia
Authors: Hahn Lisa , Rigby Ashlee , Galletly Cherrie 
Published: June 2013

Objective: This study aimed to identify factors associated with the high rates of smoking amongst people with psychosis living in a disadvantaged region in Adelaide, South Australia. Methods: Data were collected from 402 people with psychosis, aged 18–64 years, who lived in the northern suburbs of Adelaide. This area is disadvantaged on many measures of socioeconomic well-being and people living in this region have higher rates of smoking compared to the general Australian population. We hypothesised that whilst tobacco use by people with psychosis living in this region was primarily associated with mental illness, factors related to social disadvantage also contributed to the high rates of smoking. Results: Approximately 74% of men and 71% of women with psychotic disorders living in the northern suburbs of Adelaide were current smokers. Factors such as unemployment, lower levels of education and receiving government welfare, factors known to be associated with smoking in the general population, were more prevalent in the northern region. Smokers with psychosis were less likely to participate in recreational programs and physical activity, and more likely to use illicit substances and be a victim of crime. They had poorer health and financial outcomes than non-smokers. There were some gender differences: for men with psychosis, employment and having a post-school qualification decreased the risk of smoking while cannabis use increased the risk; for women with psychosis, a diagnosis of alcohol abuse/dependence, using cannabis and being sedentary were risk factors for smoking, while attending recreational programs reduced this risk. Conclusion: Smoking rates were strikingly high in both men and women, and particularly high in women when compared with previous research. Our study shows that the risk of smoking is increased by factors related to the social disadvantage of living in the northern Adelaide region. Smoking cessation interventions for people with mental illness should take into account the social context, and also address relevant comorbidities such as drug and alcohol disorders.
How perceived social support relates to suicidal ideation: A Japanese social resident survey
Authors: Endo Go , Tachikawa Hirokazu , Fukuoka Yoshiharu , Aiba Miyuki , Nemoto Kiyotaka , Shiratori Yuki , Matsui Yutaka , Doi Nagafumi , Asada Takashi 
Published: June 2013

Background: The loss of social support is one of the major risk factors for suicide. However, there are few empirical studies that have examined how a person’s suicide ideation relates to their social support. Aims: To examine the relationship between social support and suicidal ideation. Methods: Self-report questionnaires were sent to 2,200 randomly selected adults in Japan. The questionnaire inquired the participants about the severity of suicidal ideation, the details of current perceived social support and their degree of satisfaction with this social support. Social support and related indicators were compared among three groups of participants that varied in severity of suicidal ideation. Results: People in the group that had suicide ideation during their lives reported receiving significantly less support from their family and had greater feelings of dissatisfaction with that support than those in the other groups. Furthermore, people who had suicide ideation during the month immediately preceding the survey reported providing less support to their family, relatives or friends, as well as receiving less support from family than other groups, and having stronger feelings of dissatisfaction with social support. Conclusion: Our study identified a strong relationship between the severity of suicidal ideation and perceived social support.
Aesthetics of Urban Design
Authors: Paetzold Heinz 
Published: June 2013

AbstractIn the essay Aesthetics of Urban Design it is argued that contemporary aesthetics should have a base in the design of the city. It is in the everyday life of the city that people can train, exercise, improve and enlarge their aesthetic sensibilities. Given this context, two different approaches have to be distinguished. On one hand Lewis Mumford praised the medieval city as leading to the “dilation of the senses”. This is the historical approach to the question. On the other hand, however, urban design could play an important role in reconstructing the aesthetic sensibility especially today. Different reasons are relevant here. Since we can’ t presuppose that in the time after postmodernity people easily find access to the aesthetics, urban life could function as a new beginning. City life in many ways makes us acquainted with the aesthetic. The architecture of the houses, the layout of the street pattern or the atmospheres of a square have to be mentioned here. The relevance of urban design for the foundation of aesthetics can in different ways be argued from pragmatism’ s connecting the art more closely with the everyday life. John Dewey did so. But also neo-Marxism’ s idea of “sublating” art by realizing its promises in everyday life is relevant here. The essay argues that the slums, which are to be found all over the world sets some limits to the thesis that aesthetics, today, originates from urban design.