bluuebunny/crossref_metadata_2025 huggingface dataset:
What might interrupt men's suicide? Results from an online survey of men
Authors: Shand Fiona L , Proudfoot Judy , Player Michael J , Fogarty Andrea , Whittle Erin , Wilhelm Kay , Hadzi-Pavlovic Dusan , McTigue Isabel , Spurrier Michael , Christensen Helen
Published: October 2015

Objectives

Men are almost two times more likely to die by suicide than women, yet little research has focused on what is required to prevent suicide among men. This paper aims to investigate what factors interrupt suicidal behaviour in men, and to examine differences according to known suicide risk factors.

Setting

Australia.

Participants

251 Australian men aged 18 years and over who had made a suicide attempt 6–18 months prior to completing the survey.

Outcomes

The survey canvassed the language men use to describe their depression and suicidality, warning signs, barriers to accessing help and what is needed to interrupt a suicide attempt. ORs and χ2were used to test for differences by age, geographic location and current depression severity.

Results

Of 299 men screened and eligible to participate, 251 completed all or part of the survey. Participants identified different words and warning signs for depression compared with suicidality. The most commonly endorsed barriers to accessing help were not wanting to burden others (66%) and having isolated themselves (63%). Men overwhelmingly endorsed ‘I thought about the consequences for my family’ as the factor which stopped a suicide attempt (67%). ‘I need support from someone I really trust and respect’ was also strongly endorsed. There were few differences by age, region or depression severity.

Conclusions

Participants were able to identify signs, albeit often subtle ones, that they were becoming depressed or suicidal. Similarly, most were able to identify active strategies to interrupt this downward spiral. Men wanted others to notice changes in their behaviour, and to approach them without judgement.
Factors associated with variation in urgency of primary out-of-hours contacts in the Netherlands: a cross-sectional study
Authors: Zwaanswijk Marieke , Nielen Markus M J , Hek Karin , Verheij Robert A
Published: October 2015

Objectives

Dutch primary out-of-hours care is provided by general practice cooperatives (GPCs). Although most GPCs use the same standardised triage system, differences between GPCs exist in the urgency assigned to patients’ health problems. This cross-sectional study aims to provide insight into factors associated with the variation in assigned urgency between GPCs.

Design and methods

Data were derived from routine electronic health records of 895 253 patients who attended 17 GPCs in 2012. Patients’ gender, age, travel distance to the GPC, and the use of a computer-based decision support system for triage were investigated as possibly affecting assigned urgency. Multilevel linear regression analyses were executed for the 3 most frequently presented health problems (cystitis/other urinary infection, laceration/cut and fever).

Results

Variation in urgency levels between GPCs was significant for the selected health problems (p=0.00). Assigned urgency was mainly related to patient gender and age. It was not associated with the use of a computer-based decision support system, or with travel distance to the GPC. Most variation in urgency (93.4–96.7%) could be ascribed to variation in patient characteristics.

Conclusions

There is significant variation in urgency levels between GPCs, even for the same health problem. This variation is mainly associated with differences in characteristics of individuals contacting the GPCs, rather than with variables such as patients’ travel distance or the use of a computer-based decision support system. Since patient characteristics are likely to affect patients’ clinical need, our results are an indication of the adequate functioning of the triage system.
Patients’ perspectives on the medical primary–secondary care interface: systematic review and synthesis of qualitative research
Authors: Sampson Rod , Cooper Jamie , Barbour Rosaline , Polson Rob , Wilson Philip
Published: October 2015

Objectives

To synthesise the published literature on the patient experience of the medical primary–secondary care interface and to determine priorities for future work in this field aimed at improving clinical outcomes.

Design

Systematic review and metaethnographic synthesis of primary studies that used qualitative methods to explore patients’ perspectives of the medical primary–secondary care interface.

Setting

International primary–secondary care interface.

Data sources

EMBASE, MEDLINE, CINAHL Plus with Full text, PsycINFO, Psychology and Behavioural Sciences Collection, Health Business Elite, Biomedica Reference Collection: Comprehensive Library, Information Science & Technology Abstracts, eBook Collection, Web of Science Core Collection: Citation Indexes and Social Sciences Citation Index, and grey literature.

Eligibility criteria for selecting studies

Studies were eligible for inclusion if they were full research papers employing qualitative methodology to explore patients’ perspectives of the medical primary–secondary care interface.

Review methods

The 7-step metaethnographic approach described by Noblit and Hare, which involves cross-interpretation between studies while preserving the context of the primary data.

Results

The search identified 690 articles, of which 39 were selected for full-text review. 20 articles were included in the systematic review that encompassed a total of 689 patients from 10 countries. 4 important areas specific to the primary–secondary care interface from the patients’ perspective emerged: barriers to care, communication, coordination, and ‘relationships and personal value’.

Conclusions and implications of key findings

Patients should be the focus of any transfer of care between primary and secondary systems. From their perspective, areas for improvement may be classified into four domains that should usefully guide future work aimed at improving quality at this important interface.

Trial registration number

PROSPERO CRD42014009486.
Prioritising patients for bariatric surgery: building public preferences from a discrete choice experiment into public policy
Authors: Whitty Jennifer A , Ratcliffe Julie , Kendall Elizabeth , Burton Paul , Wilson Andrew , Littlejohns Peter , Harris Paul , Krinks Rachael , Scuffham Paul A
Published: October 2015

Objectives

To derive priority weights for access to bariatric surgery for obese adults, from the perspective of the public.

Setting

Australian public hospital system.

Participants

Adults (N=1994), reflecting the age and gender distribution of Queensland and South Australia.

Primary and secondary outcome measures

A discrete choice experiment in which respondents indicated which of two individuals with different characteristics should be prioritised for surgery in repeated hypothetical choices. Potential surgery recipients were described by seven key characteristics or attributes: body mass index (BMI), presence of comorbid conditions, age, family history, commitment to lifestyle change, time on the surgical wait list and chance of maintaining weight loss following surgery. A multinomial logit model was used to evaluate preferences and derive priority weights (primary analysis), with a latent class model used to explore respondent characteristics that were associated with variation in preference across the sample (see online supplementary analysis).

Results

A preference was observed to prioritise individuals who demonstrated a strong commitment to maintaining a healthy lifestyle as well as individuals categorised with very severe (BMI≥50 kg/m2) or (to a lesser extent) severe (BMI≥40 kg/m2) obesity, those who already have obesity-related comorbidity, with a family history of obesity, with a greater chance of maintaining weight loss or who had spent a longer time on the wait list. Lifestyle commitment was considered to be more than twice as important as any other criterion. There was little tendency to prioritise according to the age of the recipient. Respondent preferences were dependent on their BMI, previous experience with weight management surgery, current health state and education level.

Conclusions

This study extends our understanding of the publics’ preferences for priority setting to the context of bariatric surgery, and derives priority weights that could be used to assist bodies responsible for commissioning bariatric services.
Hearing the voices of children: self-reported information on children's experiences during research procedures: a study protocol
Authors: Staphorst Mira S , Hunfeld Joke A M , Timman Reinier , Passchier Jan , van Goudoever Johannes B
Published: October 2015

Introduction

In paediatric research, there is a tension between what you can ask from a child and what is needed for the development of evidence-based treatments. To find an optimal balance in conducting clinical research and protecting the child, it is necessary to have empirical data on children's experiences. Until now, there are scarce empirical data on the experiences from the perspective of the child. In this manuscript, we describe the protocol of a two-phase study measuring children's self-reported experiences during research procedures.

Methods and analysis

In the first phase of our study, we aim to interview approximately 40 children (6–18 years) about their self-reported experiences during research procedures. In the second phase, we will develop a questionnaire to measure children's experiences during research procedures in a quantitative way. We will use the interview outcomes for the development of this questionnaire. Next, we will measure the experiences of children during seven research procedures with this questionnaire. A one-month follow-up is conducted to investigate the emotional impact of the research procedures on the children. Children will be recruited from different research studies in three academic children's hospitals in the Netherlands.

Ethics and dissemination

The ethics committee of the VU University medical center evaluated both studies and indicated that there was no risk/discomfort associated, stating that both phases are exempt from getting approval under the Dutch Law. Dissemination of results will occur by conference presentations and peer-reviewed publications. The findings of our project can help Institutional Review Boards and paediatric researchers when evaluating the discomforts of research procedures described in study protocols or when designing a study. Information on experiences of children involved in previous studies may also help children and parents in future research with their decision-making about participation in clinical research, or parts thereof.
Telmisartan and Insulin Resistance in HIV (TAILoR): protocol for a dose-ranging phase II randomised open-labelled trial of telmisartan as a strategy for the reduction of insulin resistance in HIV-positive individuals on combination antiretroviral therapy
Authors: Pushpakom Sudeep P , Taylor Claire , Kolamunnage-Dona Ruwanthi , Spowart Catherine , Vora Jiten , García-Fiñana Marta , Kemp Graham J , Whitehead John , Jaki Thomas , Khoo Saye , Williamson Paula , Pirmohamed Munir
Published: October 2015

Introduction

Telmisartan, an angiotensin receptor blocker, has beneficial effects on insulin resistance and cardiovascular health in non-HIV populations. This trial will evaluate whether telmisartan can reduce insulin resistance in HIV-positive individuals on combination antiretroviral therapy.

Methods and analysis

This is a phase II, multicentre, randomised, open-labelled, dose-ranging trial of telmisartan in 336 HIV-positive individuals over a period of 48 weeks. The trial will use an adaptive design to inform the optimal dose of telmisartan. Patients will be randomised initially 1:1:1:1 to receive one of the three doses of telmisartan (20, 40 and 80 mg) or no intervention (control). An interim analysis will be performed when half of the planned maximum of 336 patients have been followed up for at least 24 weeks. The second stage of the study will depend on the results of interim analysis. The primary outcome measure is a reduction in insulin resistance (as measured by Homeostatic Model Assessment—Insulin Resistance (HOMA-IR)) in telmisartan treated arm(s) after 24 weeks of treatment in comparison with the non-intervention arm. The secondary outcome measures include changes in lipid profile; body fat redistribution (as measured by MRI); plasma and urinary levels of various biomarkers of cardiometabolic and renal health at 12, 24 and 48 weeks. Serious adverse events will be compared between different telmisartan treated dose arm(s) and the control arm.

Ethics and dissemination

The study, this protocol and related documents have been approved by the National Research Ethics Service Committee North West—Liverpool Central (Ref: 12/NW/0214). On successful completion, study data will be shared with academic collaborators. The findings from TAILoR will be disseminated through peer-reviewed publications, at scientific conferences, the media and through patient and public involvement.

Trial registration numbers

04196/0024/001-0001; EUDRACT: 2012-000935-18; ISRCTN: 51069819.
Patient-reported sleep disturbance in advanced cancer: frequency, predictors and screening performance of the Edmonton Symptom Assessment System sleep item
Authors: Yennurajalingam Sriram , Balachandran Dave , Pedraza Cardozo Sandra L , Berg Elyssa A , Chisholm Gary B , Reddy Akhila , DeLa Cruz Vera , Williams Janet L , Bruera Eduardo
Published: October 2015

Aims

Sleep Disturbance (SD) is a severe debilitating symptom in advanced cancer patients (ACP). However, routine screening of SD is uncommon. The primary aim of this study was to determine the optimal cutoff score for SD screening for Edmonton Symptom Assessment system (ESAS) sleep item using Pittsburgh Sleep Quality Index (PSQI) as a gold standard. We also determined the frequency of SD, obstructive sleep apnea symptoms (OSA) and restless leg syndrome (RLS) and factors associated with SD.

Methods

We prospectively surveyed 180 consecutive ACP. Patients completed validated assessment for symptoms. We determined epidemiological performance, receiver operating characteristics, and correlations of SD.

Results

SD according to PSQI was diagnosed in 112/180 (62%), and median (IQR) ESAS sleep was 5 (2-7). ESAS sleep ≥ 4 had a sensitivity of 74% and 80%, and specificity of 71% and 64% in the training and validation samples, respectively for screening of SD. The frequency of OSA was 61%; RLS was 38%. ESAS sleep was associated [r, p-value] with PSQI (0.61, <0.0001), pain (0.4, <0.0001); fatigue (0.35, <0.0001); depression (0.20, 0.006); anxiety (0.385, <0.0001); drowsiness (0.385, <0.0001), shortness of breath (0.24, <0.0014); anorexia (0.32, <0.0001), well-being (0.36, <0.0001). Multivariate analysis found well-being (OR per point 1.34, p=0.0003), pain (OR 1.21, p<0.0037), dyspnea (OR 1.16, p=0.027), and OSA (OR 0.31, P=0.003) as independent predictors of SD. There was no association between SD and survival.

Conclusions

SD is frequent and ESAS SD item ≥ 4 has good sensitivity for SD screening.
Tertiary lymphoid structures: prognostic significance and relationship with tumour-infiltrating lymphocytes in triple-negative breast cancer
Authors: Lee Hee Jin , Park In Ah , Song In Hye , Shin Su-Jin , Kim Joo Young , Yu Jong Han , Gong Gyungyub
Published: October 2015

Background

Tumour-infiltrating lymphocytes (TILs) have a strong prognostic significance, particularly in triple-negative breast cancer (TNBC). One important source of TILs in breast cancer is tertiary lymphoid structures (TLSs).

Objective

To carry out a histological analysis of surgically resected TNBC to identify the location of TLSs, the relationship between TLSs and TILs and their prognostic significance in TNBC.

Methods

We retrospectively analysed 769 patients with TNBC.

Results

TILs were defined as the percentage of stroma of invasive carcinoma infiltrated by lymphocytes. TLSs were mainly present within adjacent terminal duct lobular units and around in situ components. TNBC with higher levels of TILs showed a higher nuclear grade, lower lymphovascular invasion, less accompanying in situ component, a homogeneous growth pattern, necrosis in invasive areas, low levels of tumour stroma, high levels of peritumoral lymphocytic infiltration and moderate to abundant TLSs in adjacent tissue. TILs, the degree of peritumoral lymphocytic infiltration and adjacent TLSs were prognostic factors for disease-free and overall survival. Although the TIL level did not have a prognostic value in stage I, it added significant prognostic information for stages II and III. Conversely, patients with high levels of TILs did not show prognostic differences according to the pTNM stage. Patients with high levels of TILs (>60%) and moderate to abundant TLSs had significantly better disease-free survival than those with high levels of TILs but none or few TLSs.

Conclusions

TLSs are frequently present in TNBC and are closely associated with TILs. TILs provide additional prognostic information in patients with TNBC with a higher pTNM stage.
How stakeholder participation can contribute to systematic reviews of complex interventions
Authors: Harris J , Croot L , Thompson J , Springett J
Published: October 2015

Although patient and public involvement in research is a requirement for research funding in many countries, the knowledge base for how to effectively involve people—and evidence of the effectiveness of involvement—is weak. This article describes how methods used in participatory health research were used to involve patients, clients, providers and community health workers across all stages of a realist review. Sustained involvement enabled better identification of the components of the complex intervention of community-based peer support. It also challenged assumptions of how peer support is constructed, leading the review team to question whether the process of designing and implementing interventions has more influence on effectiveness than previously recognised in empirical studies. We conclude with a discussion on when sustained involvement should be used, and the challenges of incorporating it into the traditional researcher-led approach to systematic reviews.
Health survey of 167 pet rabbits (Oryctolagus cuniculus) in Finland
Authors: Mäkitaipale J. , Harcourt‐Brown F. M. , Laitinen‐Vapaavuori O.
Published: October 2015

Only a limited amount of information is available about health status of pet rabbits. The aim of this study was to obtain data about the health status of pet rabbits considered healthy by the owners in Finland. Physical examination and lateral abdominal and lateral skull radiography were performed on 167 pet rabbits of which 118 (70.7 per cent) had abnormal findings in at least one examination. The most common findings were acquired dental disease (n=67, 40.1 per cent), vertebral column deformities and degenerative lesions (n=52, 31.1 per cent), skin disorders (n=28, 16.8 per cent) and eye disorders (n=12, 7.2 per cent). Vertebral column angulating deformities were significantly more common in dwarf lop rabbits (P≤0.001). The prevalence of health disorders was significantly higher in rabbits over three years of age of which 51 (82.3 per cent) had findings in at least one examination (P<0.05). Rabbits as prey animals hide their illness, which cause difficulties to owners to recognise health problems. Because of the high prevalence of clinical and radiological findings in apparently healthy pet rabbits, regular physical examinations are advised, especially for animals over three years old.
The significance of tectonism in the glaciations of Greece
Authors: Bathrellos George D. , Skilodimou Hariklia D. , Maroukian Hampik
Published: October 2015

Glaciers were common features in the highlands of Greece during the Middle to Late Pleistocene glacial periods and cirques are characteristic landforms of mountain glaciation. This study examined the cirques of Greece and the role of tectonic uplift in determining their altitude across the country, from Mount Olympus to the Peloponnesus and Crete. An inventory of 227 Middle to Late Pleistocene age limestone cirques was compiled. The number and total area of the cirques decreased from northern mainland Greece (Macedonia, Epirus) to the south (the Peloponnesus, Crete) and on moving to higher elevations. Continued tectonic uplift of the Olympus massif, the Peloponnesus and Crete has led to altitudinal changes in cirques in every subsequent ice age. The formation of cirques at lower elevations during Marine Isotope Stage 12 suggests extreme climatic conditions. On Mount Olympus, the mean elevation of cirques was estimated to have increased by
c.
450 m since Marine Isotope Stage 12; in the northern and southern Peloponnesus the elevation increased by
c.
500 m and 190 m, respectively, and in Crete by
c.
400 m. The cirques have uplifted at approximately the same rate in northern Greece, but at different rates in southern Greece during this period.
Biochemical evaluation of the renin-angiotensin system: the good, bad, and absolute?
Authors: Chappell Mark C.
Published: October 2015

The renin-angiotensin system (RAS) constitutes a key hormonal system in the physiological regulation of blood pressure through peripheral and central mechanisms. Indeed, dysregulation of the RAS is considered a major factor in the development of cardiovascular pathologies, and pharmacological blockade of this system by the inhibition of angiotensin-converting enzyme (ACE) or antagonism of the angiotensin type 1 receptor (AT1R) offers an effective therapeutic regimen. The RAS is now defined as a system composed of different angiotensin peptides with diverse biological actions mediated by distinct receptor subtypes. The classic RAS comprises the ACE-ANG II-AT1R axis that promotes vasoconstriction; water intake; sodium retention; and increased oxidative stress, fibrosis, cellular growth, and inflammation. In contrast, the nonclassical RAS composed primarily of the ANG II/ANG III-AT2R and the ACE2-ANG-(1–7)-AT7R pathways generally opposes the actions of a stimulated ANG II-AT1R axis. In lieu of the complex and multifunctional aspects of this system, as well as increased concerns on the reproducibility among laboratories, a critical assessment is provided on the current biochemical approaches to characterize and define the various components that ultimately reflect the status of the RAS.
Plasticity beyond Cancer Cells and the “Immunosuppressive Switch”
Authors: Granot Zvi , Fridlender Zvi G.
Published: October 2015

Tumor initiation, growth, and metastatic progression are complex processes that, in order to be successful, require extraordinary cellular plasticity. Accordingly, tumor cell plasticity and how it affects disease progression have been studied extensively. However, as our understanding of the tumor microenvironment deepens, we are confronted with the notion that functional plasticity in the context of cancer is not limited to tumor cells alone but is also commonly seen in normal stromal cells of the microenvironment, and specifically in immune cells. Here, we review the functional plasticity these cells exhibit in the context of cancer, highlighting the role of circulating and tumor-associated neutrophils. We further discuss how this plasticity supports or limits tumor progression, inducing an “immunosuppressive switch” to promote further tumor growth and development. Cancer Res; 75(21); 4441–5. ©2015 AACR.
Tetracycline Antibiotics Impair Mitochondrial Function and Its Experimental Use Confounds Research
Authors: Chatzispyrou Iliana A. , Held Ntsiki M. , Mouchiroud Laurent , Auwerx Johan , Houtkooper Riekelt H.
Published: October 2015

Tetracyclines, a class of antibiotics that target bacterial translation, are commonly used in research for inducible gene expression using Tet-ON/Tet-OFF systems. However, such tetracycline-inducible systems carry a risk. Given that mitochondria have a “bacterial” ancestry, these antibiotics also target mitochondrial translation and impair mitochondrial function. Indeed, treatment with doxycycline—a tetracycline derivative—disturbs mitochondrial proteostasis and metabolic activity, and induces widespread gene-expression changes. Together, this affects physiology in well-established model systems ranging from cultured cells to simple organisms and to mice and plants. These changes are observed with doxycycline doses that are widely used to regulate gene expression. In light of these findings, and bearing in mind the conserved role of mitochondria in metabolism and whole organism homeostasis, we caution against the use of tetracyclines in experimental approaches. The use of newly developed tetracycline-based systems that are more sensitive could be an alternative; however, even if no overt mitochondrial toxicity is detected, widespread changes in gene expression may sensitize cells to the intended tetracycline-controlled loss or gain of function, thereby introducing a “two-hit model.” This is highly relevant for cancer research, as mitochondrial metabolism holds a central position in the reallocation of nutrients for biomass production known as the Warburg effect. Cancer Res; 75(21); 4446–9. ©2015 AACR.
The Colony-Stimulating Factor 3 Receptor T640N Mutation Is Oncogenic, Sensitive to JAK Inhibition, and Mimics T618I
Authors: Maxson Julia E. , Luty Samuel B. , MacManiman Jason D. , Paik Jason C. , Gotlib Jason , Greenberg Peter , Bahamadi Swaleh , Savage Samantha L. , Abel Melissa L. , Eide Christopher A. , Loriaux Marc M. , Stevens Emily A. , Tyner Jeffrey W.
Published: October 2015

Purpose: Colony-stimulating factor 3 receptor (CSF3R) mutations have been identified in the majority of chronic neutrophilic leukemia (CNL) and a smaller percentage of atypical chronic myeloid leukemia (aCML) cases. Although CSF3R point mutations (e.g., T618I) are emerging as key players in CNL/aCML, the significance of rarer CSF3R mutations is unknown. In this study, we assess the importance of the CSF3R T640N mutation as a marker of CNL/aCML and potential therapeutic target.

Experimental Design: Sanger sequencing of leukemia samples was performed to identify CSF3R mutations in CNL and aCML. The oncogenicity of the CSF3R T640N mutation relative to the T618I mutation was assessed by cytokine independent growth assays and by mouse bone marrow transplant. Receptor dimerization and O-glycosylation of the mutants was assessed by Western blot, and JAK inhibitor sensitivity was assessed by colony assay.

Results: Here, we identify a CSF3R T640N mutation in two patients with CNL/aCML, one of whom was originally diagnosed with MDS and acquired the T640N mutation upon evolution of disease to aCML. The T640N mutation is oncogenic in cellular transformation assays and an in vivo mouse bone marrow transplantation model. It exhibits many similar phenotypic features to T618I, including ligand independence and altered patterns of O-glycosylation—despite the transmembrane location of T640 preventing access by GalNAc transferase enzymes. Cells transformed by the T640N mutation are sensitive to JAK kinase inhibition to a similar degree as cells transformed by CSF3R T618I.

Conclusions: Because of its similarities to CSF3R T618I, the T640N mutation likely has diagnostic and therapeutic relevance in CNL/aCML. Clin Cancer Res; 22(3); 757–64. ©2015 AACR.
Global Hypomethylation (LINE-1) and Gene-Specific Hypermethylation (GSTP1) on Initial Negative Prostate Biopsy as Markers of Prostate Cancer on a Rebiopsy
Authors: Zelic Renata , Fiano Valentina , Zugna Daniela , Grasso Chiara , Delsedime Luisa , Daniele Lorenzo , Galliano Diego , Pettersson Andreas , Gillio-Tos Anna , Merletti Franco , Richiardi Lorenzo
Published: October 2015

Purpose: Men at risk of missed prostate cancer on a negative biopsy often undergo a rebiopsy. We evaluated whether global hypomethylation, measured through LINE-1 methylation, and GSTP1 hypermethylation on a negative biopsy are associated with subsequent prostate cancer diagnosis.

Experimental Design: We performed a case–control study nested in an unselected series of 737 men who received at least two prostate biopsies at least three months apart at the Molinette Hospital (Turin, Italy). Two pathology wards were included for replication purposes. The study included 67 cases and 62 controls in Ward 1 and 62 cases and 66 controls in Ward 2. We used pyrosequencing to analyze LINE-1 and GSTP1 methylation in the negative biopsies. Odds ratios (OR) of prostate cancer diagnosis were estimated using conditional logistic regression.

Results: After mutual adjustment, GSTP1 hypermethylation was associated with an OR of prostate cancer diagnosis of 5.1 (95% confidence interval: 1.7–14.9) in Ward 1 and 2.0 (0.8–5.3) in Ward 2, whereas an association was suggested only for low LINE-1 methylation levels (<70% vs. 70%–74%) with an OR of 2.1 (0.5–9.1) in Ward 1 and 1.6 (0.4–6.1) in Ward 2. When the two wards were combined the association was stronger for tumors with Gleason score ≥4+3 [GSTP1 hypermethylation: 9.2 (2.0–43.1); LINE-1 (<70% vs. 70%–74%): 9.2 (1.4–59.3)]. GSTP-1 alone improved the predictive capability of the model (P = 0.007).

Conclusions: GSTP1 hypermethylation on a negative biopsy is associated with the risk of prostate cancer on a rebiopsy, especially of high-grade prostate cancer. Consistent results were found only for extremely low LINE-1 methylation levels. Clin Cancer Res; 22(4); 984–92. ©2015 AACR.
Enzymatically Modified Low‐Density Lipoprotein Is Present in All Stages of Aortic Valve Sclerosis: Implications for Pathogenesis of the Disease
Authors: Twardowski Laura , Cheng Fei , Michaelsen Jens , Winter Stefan , Hofmann Ute , Schaeffeler Elke , Müller Simon , Sonnenberg Maike , Steuer Kristin , Ott German , Schwab Matthias , Franke Ulrich F. W. , Torzewski Michael
Published: October 2015

Background

We have demonstrated previously that enzymatically degraded low‐density lipoprotein (
eLDL
) is an essential causative component for the initiation of atherosclerosis. Here, we investigated the different stages of human aortic valve sclerosis for the presence of
eLDL
and effectors of the innate immune system, as well as the interaction of
eLDL
with isolated valvular interstitial cells/myofibroblasts to discover possible pathways leading to aortic valve sclerosis.

Methods and Results

Human aortic valvular tissue was obtained from 68 patients undergoing valve replacement surgery. Patients were classified into 3 groups (mild, moderate, or severe aortic valve sclerosis), and clinical data for statistical analysis were gathered from all patients. Immunohistochemical staining demonstrated extensive extracellular deposits of
eLDL
throughout all grades of aortic valve sclerosis. Complementary analysis of lipid composition revealed higher concentrations of the decisive components of
eLDL
(ie, unesterified cholesterol and linoleic acid) compared with internal control tissues. Further, the complement component C3d and terminal complement complexes colocalized with
eLDL
compatible with the proposal that subendothelially deposited
eLDL
is enzymatically transformed into a complement activator at early stages of valvular cusp lesion development. Gene expression profiles of proteases and complement components corroborated by immunohistochemistry demonstrated an upregulation of the protease cathepsin D (a possible candidate for
LDL
degradation to
eLDL
) and the complement inhibitor
CD
55. Surprisingly, substantial C‐reactive protein expression was not observed before grade 2 aortic valve sclerosis as investigated with microarray analysis, reverse transcription–polymerase chain reaction analysis, and immunohistochemistry. Finally, we demonstrated cellular uptake of
eLDL
by valvular interstitial cells/myofibroblasts.

Conclusions

The present study is a startup of a hypothesis on the pathogenesis of aortic valve sclerosis declaring extracellular lipoprotein modification, subsequent complement activation, and cellular uptake by valvular interstitial cells/myofibroblasts as integral players.
Differences Among Cardiologists in Rates of Positive Coronary Angiograms
Authors: Wasfy Jason H. , Hidrue Michael K. , Yeh Robert W. , Armstrong Katrina , Dec G. William , Pomerantsev Eugene V. , Fifer Michael A. , Ferris Timothy G.
Published: October 2015

Background

Understanding the sources of variation for high‐cost services has the potential to improve both patient outcomes and value in health care delivery. Nationally, the overall diagnostic yield of coronary angiography is relatively low, suggesting overutilization. Understanding how individual cardiologists request catheterization may suggest opportunities for improving quality and value. We aimed to assess and explain variation in positive angiograms among referring cardiologists.

Methods and Results

We identified all cases of diagnostic coronary angiography at Massachusetts General Hospital from January 1, 2012, to June 30, 2013. We excluded angiograms for acute coronary syndrome. For each angiogram, we identified clinical features of the patients and characteristics of the requesting cardiologists. We also identified angiogram positivity, defined as at least 1 epicardial coronary stenosis ≥50% luminal narrowing. We then constructed a series of mixed‐effects logistic regression models to analyze predictors of positive coronary angiograms. We assessed variation by physician in the models with median odds ratios. Over this time period, 5015 angiograms were identified. We excluded angiograms ordered by cardiologists requesting <10 angiograms. Among the remaining 2925 angiograms, 1450 (49.6%) were positive. Significant predictors of positive angiograms included age, male patients, and peripheral arterial disease. After adjustment for clinical variables only, the median odds ratio was 1.23 (95%
CI
1.0–1.36), consistent with only borderline clinical variation after adjustment. In the full clinical and nonclinical model, the median odds ratio was 1.07 (95%
CI
1.07–1.20), also consistent with clinically insignificant variation.

Conclusions

Substantial variation exists among requesting cardiologists with respect to positive and negative coronary angiograms. After adjustment for clinical variables, there was only borderline clinically significant variation. These results emphasize the importance of risk adjustment in reporting related to quality and value.
Metacommunication in social play: the meaning of aggression-like elements is modified by play face in Hanuman langurs (Semnopithecus entellus)
Authors: Špinka Marek , Palečková Marie , Řeháková Milada
Published: October 2015

The metacommunication hypothesis asserts that some elements of play behaviour are associated with play elements borrowed from aggression and interpret these aggression-like elements as playful. Using data from free living Hanuman langurs (Semnopithecus entellus), we tested three predictions that follow from the metacommunication hypothesis: (i) aggression-like elements (ALEs) abbreviate play bouts; (ii) candidate signal elements are sequentially associated with ALEs; (iii) associations of candidate signal elements with ALEs prolong play bouts. Play face and five other candidate signal elements were evaluated in relation to nine ALEs. We confirmed all three predictions for play face, albeit only if the play face and/or the ALEs occurred at the start of the play bout. The other candidate elements were not associated with ALEs. We conclude that play face fulfils the metacommunicatory function in Hanuman langur play bouts, while other play specific elements may serve other signal or non-signal functions.
Classification of Aortic Stenosis by Flow and Gradient Patterns Provides Insights into the Pathophysiology of Disease
Authors: Bhattacharyya Sanjeev , Mittal Tarun , Abayalingam Mayavan , Kabir Tito , Dalby Miles , Cleland John G. , Baltabaeva Aigul , Rahman Haley Shelley
Published: October 2015

Different patterns of flow and valve gradients can lead to diagnostic uncertainty about the severity of aortic stenosis (AS). Consecutive patients with severe AS (valve area <1 cm2) underwent echocardiography and computed tomography. Patients were classified into 4 groups (high-gradient/normal flow [HGNF], high-gradient/low flow [HGLF], low-gradient/normal flow [LGNF], and low-gradient/low flow [LGLF]). Low flow was defined as stroke volume index <35 mL/m2 and low gradient as a mean aortic gradient <40 mm Hg. Aortic valve calcification (AVC) was calculated using the Agatston score. Of 181 patients, 56, 30, 46, and 49 had HGNF, HGLF, LGNF and LGLF with median AVC of 2048, 2015, 1366, and 1178 AU/m2 ( P < .0001) and valvuloarterial impedance of 4.5, 6.4, 4.2, and 5.9, respectively ( P < .0001). Among those with LGLF, AVC was lower in patients with preserved compared to reduced left ventricular ejection fraction (1018 vs 2550 AU/m2; P < .0001), but valvuloarterial impedance was similar ( P = .33). The LGLF AS with preserved ejection fraction is associated with lower AVC and may identify patients with less severe AS in association with an adaptive ventricular response to high afterload.
Diagnosis of Pediatric Foreign Body Ingestion
Authors: Sink Jacquelyn R. , Kitsko Dennis J. , Mehta Deepak K. , Georg Matthew W. , Simons Jeffrey P.
Published: October 2015

Objectives:

(1) To describe clinical and radiologic findings in patients with esophageal foreign bodies. (2) To examine the sensitivity and specificity of history, physical examination, and radiologic studies in children with suspected foreign body ingestion.

Methods:

A retrospective cohort study was performed evaluating all children who underwent esophagoscopy for suspected foreign body ingestion at our institution from 2006 to 2013.

Results:

Five hundred forty-three patients were included (54% male). Average age was 4.7 years (SD = 4.1 years). Foreign bodies were identified on esophagoscopy in 497 cases (92%). Ingestion was witnessed in 23% of cases. Most common presenting symptoms were choking/gagging (49%), vomiting (47%), and dysphagia/odynophagia (42%). Most patients with foreign bodies had a normal exam (76%). Most foreign bodies were radiopaque (83%). In 59% of patients with normal chest radiographs, a foreign body was present. Sensitivity and specificity of 1 or more findings on history, physical examination, and imaging were 99% and 0%, 21% and 76%, and 83% and 100%, respectively.

Conclusions:

Most patients with esophageal foreign bodies are symptomatic. Although many patients will have a normal physical examination, an abnormal exam should increase suspicion for a foreign body. Most esophageal foreign bodies are radiopaque, but a normal chest radiograph cannot rule out a foreign body.
The Penalization of Non-Communicating UN Global Compact’s Companies by Investors and Its Implications for This Initiative’s Effectiveness
Authors: Amer Estefania
Published: October 2015

Companies that have joined the United Nations Global Compact (UNGC) are required to submit a Communication on Progress (COP), which is an environmental, social, and governance (ESG) report, to the UNGC every year. If they fail to do so, they are marked and listed as non-communicating on the UNGC website. Using the event study methodology, this study shows that a company that fails to report to the UNGC is penalized in the financial markets with an average cumulative abnormal return of −1.6% over a period of 5 trading days around the event. Although a major critique against the UNGC is that the initiative’s voluntary nature and its lack of external monitoring and sanction mechanisms render it ineffective in terms of the business participants’ implementation of the UNGC principles into their operations, this result suggests that investors may be able to pressure UNGC business participants to increase their compliance with the UNGC requirements and to “walk the talk.”
Corporate Boards and Ownership Structure as Antecedents of Corporate Governance Disclosure in Saudi Arabian Publicly Listed Corporations
Authors: Al-Bassam Waleed M. , Ntim Collins G. , Opong Kwaku K. , Downs Yvonne
Published: October 2015

This study investigates whether and to what extent publicly listed corporations voluntarily comply with and disclose recommended good corporate governance (CG) practices, and distinctively examines whether the observed cross-sectional differences in such CG disclosures can be explained by ownership and board mechanisms with specific focus on Saudi Arabia. The study’s results suggest that corporations with larger boards, a Big 4 auditor, higher government ownership, a CG committee, and higher institutional ownership disclose considerably more than those that are not. By contrast, the study finds that an increase in block ownership significantly reduces CG disclosure. The study’s results are generally robust to a number of econometric models that control for different types of disclosure indices, firm-specific characteristics, and firm-level fixed effects. The study’s results have important implications for policy makers, practitioners, and regulatory authorities, especially those in developing countries across the globe.
E-Reading and the Christian Bible
Authors: Hutchings Tim
Published: October 2015

The Christian Bible is now available in thousands of digital forms, re-imagined for electronic reading on mobile, tablet and desktop screens. This article introduces findings from an online survey of digital Bible users, analysing their demographics, reading practices, motivations and experiences. Survey responses are analysed in conversation with recent debates among Christian commentators and broader arguments in the study of e-reading in education and other contexts. Religious e-reading shows some distinctive and unexpected features, in comparison with reading in other contexts, and this article proposes some initial hypotheses about the impact of digital media on sacred text.
Unpacking Ethnic Preferences
Authors: Chauchard Simon
Published: October 2015

Much of the recent scholarship about ethnicity in comparative politics has focused on why ethnicity becomes a salient cleavage. Yet opinions still diverge as to how ethnicity matters. This article tests three hypotheses relevant to this question. Building on recent arguments, it first hypothesizes that voters take the ethnicity of parties and candidates into consideration. Second, it hypothesizes that wherever ethnicity is politically salient, it matters beyond coethnicity—that is, voters’ decisions are guided by ethnicity even when they are choosing among non-coethnics. Third, it argues that the advantage conferred by ethnicity is mediated by non-ethnic factors. A large vignette experiment carried in 2013 in the Indian state of Uttar Pradesh provides strong support for each of these hypotheses. These results imply that the influence of ethnicity on voting behavior may be subtler and more complex than what the main theories of ethnic politics usually assume.
“I am a father now”: Colonial paternalism and oedipal typicality in Shaun Johnson’s The Native Commissioner
Authors: Emmett Christine
Published: October 2015

This article considers the prevalence and dynamics of colonial paternalism and oedipal typicality as they operate within Shaun Johnson’s novel, The Native Commissioner (2006). Therefore, the article explicates how Freud’s oedipal theory can, read within its historical context, contribute and serve as a tool to elucidate colonial discourses. It also indicates the prevalence of colonial paternalism, not merely through the South African Union government (1910–1961) and apartheid, but as I will argue, within post-apartheid South Africa. Johnson’s novel, which presents a father–son narrative, interfaces with colonial paternalism through the father, George Jameson, and his role as a Native Commissioner. Through an analysis of the ideological assumptions underlying George’s identity as a father (and associated notions of husbandry, gardening, and cultivation), the shared ideological basis of his career as a Native Commissioner and his seemingly neutral role as a patriarch is highlighted. The article then considers how oedipal dynamics structure the novel’s focus on paternalism. Through an analysis of George’s failure as a patriarch and the psychically invested nature of the narrative, we encounter the concomitant anxiety of the son-as-narrator. This anxiety manifests itself in the oedipal mechanics of castration anxiety, rivalry, and identification as originally explicated by Freud. Through these mechanics, the power of the son-as-narrator is emphasized as the father dies and the son identifies with the father’s power. The remainder of the article re-contextualizes these findings within the novel’s reception by South African audiences. The novel’s popularity suggests that colonial paternalism remains a discourse that still has significant purchase for white South Africans even amid calls to identities based on equality and multiculturalism.
Is Marijuana Use Associated With Health Promotion Behaviors Among College Students? Health-Promoting and Health-Risk Behaviors Among Students Identified Through Screening in a University Student Health Services Center
Authors: Palfai Tibor P. , Tahaney Kelli D. , Winter Michael R.
Published: October 2015

This study sought to examine whether student marijuana use identified by screening in a student health center is associated with health-promoting behaviors. Students completed a brief web-based, health behavior screening instrument. Those who reported marijuana use of monthly or more on the Alcohol, Smoking, and Substance Involvement Test (ASSIST)—and a subset of those who did not—were invited to complete additional baseline assessments, including questions about health-promoting behaviors, alcohol, and substance use ( n = 321). Results showed marijuana users were more likely to use a variety of substances and engage in hazardous drinking than non-users. Moreover, level of marijuana use was associated with greater likelihood of using a variety of substances but not with hazardous drinking. There was no evidence that marijuana use was associated with health-promoting behaviors. These findings highlight the concomitant substance-related risks associated with marijuana use but do not support the view that these students are less likely to engage in health-promoting behaviors than non-users.
Rapid Naming and Phonemic Awareness in Children With or Without Reading Disabilities and/or ADHD
Authors: De Groot Barry J. A. , Van den Bos Kees P. , Van der Meulen Bieuwe F. , Minnaert Alexander E. M. G.
Published: October 2015

Employing a large sample of children from Dutch regular elementary schools, this study assessed the contributing and discriminating values of reading disability (RD) and attention-deficit/hyperactivity disorder (ADHD) to two types of phonological processing skills, phonemic awareness (PA) and rapid automatized naming (RAN). A second objective was to investigate whether comorbidity of RD and ADHD should be considered as an additive phenomenon as to RAN and PA. A total of 1,262 children, aged 8 to 13 years, were classified as RD ( n = 121), ADHD ( n = 17), comorbid (RD+ADHD; n = 16), or control ( n = 1,108). Phonological processing was assessed by standardized tests of PA and RAN. Disability groups were compared to each other and contrasted to the control group. Although results indicate substantial effects for all three disability groups on both types of phonological processing, and the RAN/PA compound measure in particular, effect sizes were considerably larger for the RD groups, as compared to the ADHD-only group. Theoretical and practical implications are discussed.
Group-based Trajectory Modeling and Criminal Career Research
Authors: Nagin Daniel S.
Published: October 2015

This essay traces the origins of group-based trajectory modeling (GBTM) from its inception as a statistical tool for analyzing issues central to the criminal careers debate of the 1990s to its widespread application outside of criminology especially in psychological and medical research to study the developmental course of disease and physiological processes. Also, discussed are common misconceptions about the interpretation of GBTM.