bluuebunny/crossref_metadata_2025_split huggingface dataset:
VALIDATION OF STANDARDIZATION METHODOLOGY TO MINIMIZE MEASUREMENT BIAS DUE TO SYSTEMATIC ACCELEROMETER WEAR-TIME VARIATION IN PRESCHOOLERS, ADOLESCENTS, AND ADULTS
Authors: Katapally Tarun , Froehlich-Chow Amanda , Leis Anne , Humbert Louise , Muhajarine Nazeem 
Published: September 2013

IntroductionIncreasingly, physical activity (PA) and sedentary behaviour (SED) are independently being associated with physical, mental and emotional well-being. The heightened research interest in this area has resulted in an upsurge of accelerometer usage to objectively quantify PA and SED. However, these epidemiological investigations consistently ignore systematic variation in the number of hours participants wear accelerometers each day (i.e., systematic accelerometer wear-time variation), and this has a direct impact on measured activity.ObjectivesUsing three different cohorts (3–5 years ─ N=83; 10-14years ─ N=455; and 18 years and older ─ N=21), this study aims to validate a standardization methodology to minimize measurement bias due to accelerometer wear-time variation.MethodsIn epidemiological studies, accelerometry is generally conducted over seven consecutive days, and participants' data are considered 'valid' only if wear-time is at least 10 hours/day. However, there could be systematic wear-time variation even within 'valid' data. To explore this variation, accelerometer data from two studies set in Saskatoon, Saskatchewan were analyzed: Smart Cities, Healthy Kids (smartcitieshealthykids.com) and Healthy Start (http://www.canadainmotion.ca/healthy_start/). Subsequently, a standardization method was developed where case-specific observed wear-time was controlled for using an ‘analyst specified’ time period. Next, case-specific accelerometer data were interpolated to this controlled wear-time to produce standardized variables. To understand discrepancies owing to wear-time variation, identical analyses were conducted with data from all three cohorts both pre- and post-standardization. The results of these identical analyses were compared to objectively validate the standardization methodology.ResultsIn all three cohorts, descriptive analyses revealed systematic wear-time variation between participants. Again, in all three cohorts, pre- and post-standardized analyses of the three outcome variables (SED, light physical activity and moderate vigorous physical activity) that cover the whole range of human activities revealed an identical and often significant trend of wear-time's influence on activity. For instance, SED which was consistently higher during weekdays pre-standardization, proved to be higher during weekends post-standardization.ConclusionsAnalyzing accelerometer data without standardizing wear-time will cause biased results and erroneous conclusions. Standardizing accelerometer data using the above mentioned methodology produces stable variables and a uniform platform to compare results between studies, irrespective of the studies' sample size or age characteristics.
LIFECOURSE ANALYSIS OF MANUAL OCCUPATIONS AND RISK OF PROSTATE CANCER IN MONTREAL, CANADA: A CASE-CONTROL STUDY
Authors: Blaser Christine , Nicolau Belinda , Parent Marie-Élise 
Published: September 2013

IntroductionCancer risk factors accumulate over time or affect the body at specific moments of development. Our lifecourse approach identified occupational exposures and social determinants of health associated with the risk of prostate cancer across a lifetime.ObjectivesTo assess the risk of prostate cancer among men employed in manual occupations compared to the risk of those in non-manual occupations. Using three time points of exposure, we tested the accumulation, critical period and trajectory models.MethodsHistologically-confirmed prostate cancer cases (n=1229), aged 40 to 75, were identified across 11 French hospitals in Montreal. Population controls (n=1307) were identified from the French provincial electoral list in the same areas of residence as the cases, and frequency-matched to cases by age (± 5 years). Information on socio-demographic, lifestyle characteristics, and detailed occupational history, was collected through face-to-face interviews. Using the British Registrar General's classification of occupations, jobs held at age 25 and 55, and father's occupation at birth, were categorised as manual or non-manual. Logistic regression models were applied.ResultsMen with exposure to manual occupations at the three time points were more likely to have had an unfavourable financial situation during childhood, a lower education level and a lower family income at diagnosis or interview. Based on the accumulation model, men who held only manual occupations were at 23% excess risk of prostate cancer [OR=1.23, 95%CI 1.00–1.51] compared to those who did not after controlling for other socioeconomic factors. Using the trajectory model, a decreased risk of prostate cancer [OR=0.79, 95%CI 0.59–1.05] was observed among men moving from manual to non-manual occupations during adulthood. The critical period model did not identify any risk differences when exposures occurred specifically at one of the three time points.ConclusionAlthough life-course models are difficult to disentangle, the observed associations between manual occupations and prostate cancer risk are consistent with both accumulation and trajectory models. Highest risks were observed with prolonged exposure to manual occupations. Conversely, moving from manual to non-manual occupations appeared to be protective against prostate cancer.
PREDICTING THE OCCURRENCE OF MAJOR ADVERSE CARDIAC EVENTS WITHIN 30 DAYS AFTER A PATIENT'S VASCULAR SURGERY: AN INDIVIDUAL PATIENT-DATA META-ANALYSIS
Authors: Vanniyasingam Thuvaraha , Thabane Lehana , Rodseth Reitze , Buse Giovana A. Lurati , Bolliger Daniel , Daniel Christoph S. , Cuthbertson Brian H. , Gibson Simon C. , Mahla Elisabeth , Leibowitz David W. , Biccard Bruce 
Published: September 2013

IntroductionMajor adverse cardiac events (MACE) – which include cardiac death and non-fatal myocardial infarction – are severe harmful outcomes that commonly arise after elective non-cardiac vascular surgeries. Current preoperative risk prediction models are not as effective in predicting post-operative outcomes. This talk will discuss the key results of an individual patient-data meta-analysis, based on data from six cohort studies of patients undergoing vascular surgery.ObjectivesWe aimed to determine a prediction model that dichotomizes patients into high and low risk categories of MACE within 30 days after noncardiac vascular surgery.ApproachThis is an application of the minimum p-value method (MPM) to determine the optimal cut-off points for: (i) B-type naturietic peptide (BNP) and (ii) N-terminal pro B-type natriuretic peptide (NTproBNP) in predicting MACE within 30 days after non-cardiac vascular surgery. Elevated concentrations of these hormones are secreted into the blood in response to heart failure. We compare results from MPM with those based on the receiver operating characteristic (ROC) curve approach using logistic regression; develop and validate the prediction rule for MACE; and assess the robustness of the results under different statistical models.ResultsThe ROC curve approach (applied by Rodseth and colleagues) identified 116pg/mL and 277.5pg/mL as the optimal thresholds for BNP and NTproBNP, respectively. The minimum p-value method dichotomized these covariates as BNP: 115.57pg/mL (p<0.0001) and NTproBNP: 241.7pg/mL (p=0.0001). Our logistic regression analysis identified MINP_thrshld, the indicator variable of our MPM results for BNP and NTproBNP, as a stronger covariate than our ROC curve results. Our final prediction model contained variables MINP_thrshld, the type of surgery, and diabetes mellitus. Internal validation was performed using bootstrapping while mixed effects logistic regression and generalized estimating equations were performed for sensitivity analysis. Although our model was validated using 1000 samples, it was not robust against methods that accounted for clustering effects.ConclusionAs current preoperative risk stratification models are not as effective in predicting post-operative outcomes for vascular surgery patients, clinicians are at an advantage in using this model for the ease and accuracy that it provides. Further exploration into clustering effects is needed for determining the best model.
ASSOCIATION OF C-REACTIVE PROTEIN WITH METABOLIC SYNDROME AND DEPRESSIVE SYMPTOMS IN THE ENGLISH LONGITUDINAL STUDY OF AGEING
Authors: Au Bonnie , Schmitz Norbert 
Published: September 2013

IntroductionThe metabolic syndrome is a cluster of risk factors comprised of elevated fasting plasma glucose and insulin resistance, central obesity, low levels of high-density lipoprotein cholesterol, hypertriglyceridemia, and hypertension. Depression is a common co-morbidity in individuals with metabolic syndrome. Inflammatory mechanisms have been suggested to be involved in depression and metabolic syndrome. C-reactive protein (CRP), an acute-phase reactant of systemic inflammation, has been found to be independently associated with metabolic syndrome and depression.ObjectivesTo assess the association between C-reactive protein with metabolic syndrome and depressive symptoms in a representative sample of British people aged 50 years and above.MethodsParticipants were 8398 men and women from the English Longitudinal Study of Ageing(ELSA), a prospective study of community-dwelling older adults. Associations between CRP with metabolic syndrome and depressive symptoms were examined using stratified multivariate logistic regression adjusted for age, smoking, physical activity, and alcohol consumption. Metabolic syndrome was based on the new worldwide definition by the International Diabetes Federation (IDF). Elevated depressive symptoms was based on a score >=4 using the 8-item Center for Epidemiologic Studies Depression Scale (CES-D) scale.ResultsThe prevalence of having both metabolic syndrome and elevated depressive symptom was 27.5%. Preliminary results indicate that high CRP levels is associated with elevated depressive symptoms in individuals without metabolic syndrome (adjusted OR: 2.23, 95% CI: 1.65-3.02), but not in individuals with metabolic syndrome. High CRP levels is associated with metabolic syndrome in individuals with elevated depressive symptoms (adjusted OR: 3.41, 95% CI: 2.48-4.69) as well as in individuals without elevated depressive symptoms (adjusted OR: 3.46, 95% CI: 2.37-5.05).ConclusionsMetabolic syndrome and depressive symptoms are independently related to CRP. A better understanding using longitudinal data will help assess whether inflammation is a determinant of depressive symptoms in individuals with metabolic syndrome.
ANTIBIOTIC STEWARDSHIP PROGRAM; CONTEXTUAL ENVIRONMENT AND FRAMEWORK
Authors: Al-Khatib Naser , Cholin Brenda , Moraros John 
Published: September 2013

IntroductionAntibiotic Stewardship is currently an important topic in Public Health, Hospital Epidemiology and Infectious Disease Epidemiology. Designing, implementing and evaluating an Antibiotic Stewardship Program (ASP) is mandates by accreditation agencies. Prairie North Regional Health Authority (PNRHA)- Saskatchewan assigned me to collect and analyse quantitatively and qualitatively - data related to antibiotic prescription habits of physicians in three hospitals and community clinics.Objectives1- to review the literature on antibiotic Stewardship and its programs 2- to understand the local antibiotics prescribing environment (using one 2010 data) 3- to design an Antibiotic Stewardship Program for the PNRHAMethodsData collection by direct key stakeholders interviews, using hospital pharmacy, the lab and admission information systems. Community data were sourced from Saskatchewan Drug Plan administration - Using Excel and SPSS for data management, and biostatistics (parametric, non-parametric and variance analysis) - Using results for evidence based design of an Antibiotic Stewardship ProgramResultsThe detailed descriptive statistics were very helpful to draw a baseline. These descriptive statistics shed the light on usage of 33 antibiotics in three different hospitals. These results were categorized based on specialty, main groups of antibiotics, per doctor, per antibiotic, per DOT (Duration of Therapy) and DOT per 1000 patient-day.ConclusionsThere were recommendations on how to adopt the Antibiotic Stewardship and the suggested framework, as well as recommendations about data collection, analysis and measurements for future implementation of the Program. Specific steps were encouraged based on the exact results of specific antibiotics such as flouroquinolones, clindamycin, vancomycin and IV administration and conversion to oral antibiotics
FETAL ALCOHOL SPECTRUM DISORDER: COST OF SCREENING AND DIAGNOSIS IN CANADA
Authors: Lange Shannon , Burd Larry , Chudley Albert E. , Clarren Sterling K. , Rehm Jürgen , Popova Svetlana 
Published: September 2013

IntroductionsPrenatal alcohol exposure can lead to a myriad of adverse health outcomes for the child, including Fetal Alcohol Spectrum Disorder (FASD). Unfortunately, for a number of reasons, FASD is underdiagnosed in many countries, including Canada. The diagnosis of FASD is not simple and is a time consuming process that should be done via a comprehensive, multidisciplinary assessment of the individual.ObjectivesTo estimate the per person and the annual cost of FASD screening diagnostic services in Canada.MethodsThe breakdown of the diagnostic process was based on the Fetal Alcohol Spectrum Disorder: Canadian Guidelines for Diagnosis. In order to calculate the per person cost of diagnosis, the number of hours required by each specialist involved in the diagnostic process were estimated, and the average rate per hour for each specialist was applied to the respective number of hours needed. The existing clinical capacity of all FASD multidisciplinary clinics in Canada, obtained from the 2005 and 2011 surveys conducted by the Canada Northwest FASD Research Network, was used to estimate the number of FASD cases diagnosed per year in Canada. The per person cost of FASD diagnosis was applied to the total number of FASD cases diagnosed per year in order to calculate the annual cost of FASD diagnostic services in Canada.ResultsIt was estimated that a comprehensive, multidisciplinary FASD assessment requires 32 to 47 hours, resulting in a total cost of $3,110 to $4,570 per person. Based on a clinical capacity of 2,288 in Canada per year, and assuming that 50% (lower estimate) to 70% (upper estimate) of all individuals evaluated are diagnosed with FASD, it was calculated that 1,602 to 1,144 cases of FASD are diagnosed per year in Canada. As such, it was estimated that the cost of all FASD screening and diagnostic services in Canada ranges from $3.6 to $5.2 million (lower estimate), up to $5.0 to $7.3 million (upper estimate) per year.ConclusionsCost of FASD screening and diagnostic services is high in Canada. However, this economic burden is largely avoidable given that FASD is preventable if effective policies are implemented.
Circular RNA and miR-7 in Cancer
Authors: Hansen Thomas B. , Kjems Jørgen , Damgaard Christian K. 
Published: September 2013

Abstract
MicroRNAs (miRNA) play important roles in fine-tuning gene expression and are often deregulated in cancer. The identification of competing endogenous RNA and circular RNA (circRNA) as important regulators of miRNA activity underscores the increasing complexity of ncRNA-mediated regulatory networks. Particularly, the recently identified circular RNA, ciRS-7, which acts as a designated miR-7 inhibitor/sponge, has conceptually changed the mechanistic understanding of miRNA networks. As miR-7 modulates the expression of several oncogenes, disclosing the regulation of miR-7 activity will likely advance the understanding of various cancer etiologies. Here, we review the current knowledge about the ciRS-7/miR-7 axis in cancer-related pathways and discuss possible models explaining the relevance of coexpressing miR-7 along with a circRNA inhibitor. Cancer Res; 73(18); 5609–12. ©2013 AACR.
Antitumor Immunity: Easy as 1, 2, 3 with Monoclonal Bispecific Trifunctional Antibodies?
Authors: Maher John , Adami Antonella A. 
Published: September 2013

AbstractMonoclonal antibodies occupy an increasing niche in the arsenal available to treat cancer. Several developments have rendered this the fastest growing sector in the pharmaceutical industry. Traditionally, antibodies were developed to block key signaling molecules implicated in tumor progression. However, antibodies also recruit additional immune effector mechanisms against tumors, a property that may be exploited for clinical benefit. Bispecific antibodies represent one such strategy in which elements derived from two monoclonal antibodies are incorporated into a single molecular species. Commonly, the bispecific approach is used to achieve simultaneous cross-linking of CD3 and a tumor antigen such as epithelial cell adhesion molecule (EpCAM), thereby recruiting T-cell activation to the tumor cell surface. A further sophistication involves the engineering of trifunctional derivatives such as the clinically approved agent, catumaxomab. Catumaxomab has antigen-binding arms that engage CD3 and EpCAM and a constant domain that recruits Fc receptor-bearing cells, notably monocytes, dendritic cells, and natural killer cells. Owing to this triangular binding capability, catumaxomab can activate both innate and adaptive immune effector mechanisms in addition to promoting immunologic memory. Recent data indicate that this agent can also promote immunogenic cell death, particularly when used in combination with selected chemotherapeutic agents such as oxaliplatin. Cancer Res; 73(18); 5613–7. ©2013 AACR.
miRNA-141, Downregulated in Pancreatic Cancer, Inhibits Cell Proliferation and Invasion by Directly Targeting MAP4K4
Authors: Zhao Gang , Wang Bo , Liu Yang , Zhang Jun-gang , Deng Shi-chang , Qin Qi , Tian Kui , Li Xiang , Zhu Shuai , Niu Yi , Gong Qiong , Wang Chun-you 
Published: September 2013

Abstract
miRNAs are associated with various types of cancer due to their ability to affect expression of genes that modulate tumorigenesis. In this study, we explored the role of miR-141 in pancreatic cancer. The analysis of clinical characteristics showed that miR-141 was significantly downregulated in tissues and cell lines of pancreatic cancer. Moreover, the decreased miR-141 level was significantly associated with tumor size and TNM stage, as well as lymph node and distant metastasis. Meanwhile, both Kaplan–Meier and multivariate survival analysis showed decreased miR-141 were associated with overall survival. Overexpression of miR-141 in pancreatic cancer cells inhibited cell proliferation, clonogenicity, and invasion; induced G1 arrest and apoptosis; and enhanced chemosensitivity. To understand how miR-141 mediates the phenotype of pancreatic cancer cells, a bioinformatics tool was used to identify MAP4K4 as a potential target of miR-141. The Dual-Luciferase reporter gene assay showed that miR-141 binds directly to the 3′-untranslated region (3′UTR) of MAP4K4 to inhibit MAP4K4 expression. Western blot and quantitative real-time PCR (qRT-PCR) analyses revealed that MAP4K4 expression was inversely correlated with miR-141 expression both in pancreatic cancer samples and cell lines. Knockdown of MAP4K4 inhibited cell proliferation, clonogenicity, and invasion, induced G1 arrest and apoptosis, and enhanced chemosensitivity. In a nude mouse xenograft model, both overexpression of miR-141 and knockdown of MAP4K4 significantly repressed pancreatic cancer cell growth. Therefore, we conclude that miR-141 targets MAP4K4, acts as a tumor suppressor in pancreatic cancer cells, and may serve as a novel therapeutic agent for miRNA-based pancreatic cancer therapy. Mol Cancer Ther; 12(11); 2569–80. ©2013 AACR.
Impact of Ejection Fraction on the Clinical Response to Cardiac Resynchronization Therapy in Mild Heart Failure
Authors: Linde Cecilia , Daubert Claude , Abraham William T. , St John Sutton Martin , Ghio Stefano , Hassager Christian , Herre John M. , Bergemann Tracy L. , Gold Michael R. 
Published: September 2013

Background—
Current guidelines recommend cardiac resynchronization therapy (CRT) in mild heart failure (HF) patients with QRS prolongation and ejection fraction (EF) ≤30%. To assess the effect of CRT in less severe systolic dysfunction, outcomes in the REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction (REVERSE) study were evaluated in which patients with left ventricular (LV) ejection fraction (LVEF) >30% were included.

Methods and Results—

The results of patients with baseline EF >30% (n=177) and those with EF ≤30% (n=431), as determined by a blinded core laboratory, were compared. In the LVEF >30% subgroup, there was a trend for improvement in the clinical composite response with CRT ON versus CRT OFF (
P
=0.06) and significant reductions in LV end systolic volume index (−6.7±21.1 versus 2.1±17.6 mL/m
2
;
P
=0.01) and LV mass (−20.6±50.5 versus 5.0±42.4 g;
P
=0.04) after 12 months. The time to death or first HF hospitalization was significantly prolonged with CRT (hazard ratio, 0.26;
P
=0.012). In the LVEF <30% subgroup, significant improvements in clinical composite response (
P
=0.02), reverse remodeling parameters, and time to death or first HF hospitalization (hazard ratio, 0.58;
P
=0.047) were observed. After adjusting for important covariates, the CRT ON assignment remained independently associated with improved time to death or first HF hospitalization (hazard ratio, 0.54;
P
=0.035), whereas there was no significant interaction with LVEF.

Conclusions—
Among subjects with mild HF, QRS prolongation, and LVEF >30%, CRT produced reverse remodeling and similar clinical benefit compared with subjects with more severe LV systolic dysfunction.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00271154.
Do Outcomes for Patients With Heart Failure Vary by Emergency Department Volume?
Authors: Brar Sandeep , McAlister Finlay A. , Youngson Erik , Rowe Brian H. 
Published: September 2013

Background—
Heart failure is a common Emergency Department (ED) presentation but whether ED volume influences patient outcomes is unknown.

Methods and Results—
Retrospective cohort of all adults presenting to 93 EDs between 1999 and 2009 with a most responsible diagnosis of heart failure (n=44 925 ED visits; mean age, 76.4 years). Cases seen in low-volume EDs had less comorbidities and were less likely to be hospitalized (54.5%) than those seen in medium (61.8%; adjusted odds ratio [aOR] 1.16, [95% confidence interval {CI} 1.10–1.23]) or high-volume EDs (73.6%; aOR, 1.95 [95% CI, 1.83–2.07]). Of patients treated and released, low-volume ED cases exhibited higher risk of death/hospitalization/ED visit in the subsequent 7 (22.0%) and 30 days (44.9%) than medium (16.3%; aOR, 0.81 [95% CI, 0.73–0.90], and 35.3%; aOR, 0.79 [95% CI, 0.73–0.86]) or high-volume ED cases (13.0%; aOR, 0.69 [95% CI, 0.61–0.78], and 30.2%; aOR, 0.67 [95% CI, 0.61–0.74]). Of patients hospitalized at the time of their index ED visit, low-volume ED cases exhibited a higher risk of 30-day death/all-cause readmission (24.3%) than those seen in medium (21.9%; aOR, 0.83 [95% CI, 0.76–0.91]) or high-volume EDs (18.1%; aOR, 0.77 [95% CI, 0.70–0.85]).

Conclusions—
Low-volume EDs were more likely to discharge patients with heart failure home, but low-volume ED cases exhibited worse outcomes (driven largely by readmissions or repeat ED visits). Interventions to improve management of acute heart failure are required at low-volume sites.