bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhanced Targeting of the EGFR Network with MM-151, an Oligoclonal Anti-EGFR Antibody Therapeutic
Authors: Kearns Jeffrey D. , Bukhalid Raghida , Sevecka Mark , Tan Gege , Gerami-Moayed Nastaran , Werner Shannon L. , Kohli Neeraj , Burenkova Olga , Sloss Callum M. , King Anne M. , Fitzgerald Jonathan B. , Nielsen Ulrik B. , Wolf Beni B.
Published: April 2015

Although EGFR is a validated therapeutic target across multiple cancer indications, the often modest clinical responses to current anti-EGFR agents suggest the need for improved therapeutics. Here, we demonstrate that signal amplification driven by high-affinity EGFR ligands limits the capacity of monoclonal anti-EGFR antibodies to block pathway signaling and cell proliferation and that these ligands are commonly coexpressed with low-affinity EGFR ligands in epithelial tumors. To develop an improved antibody therapeutic capable of overcoming high-affinity ligand-mediated signal amplification, we used a network biology approach comprised of signaling studies and computational modeling of receptor–antagonist interactions. Model simulations suggested that an oligoclonal antibody combination may overcome signal amplification within the EGFR:ERK pathway driven by all EGFR ligands. Based on this, we designed MM-151, a combination of three fully human IgG1 monoclonal antibodies that can simultaneously engage distinct, nonoverlapping epitopes on EGFR with subnanomolar affinities. In signaling studies, MM-151 antagonized high-affinity EGFR ligands more effectively than cetuximab, leading to an approximately 65-fold greater decrease in signal amplification to ERK. In cell viability studies, MM-151 demonstrated antiproliferative activity against high-affinity EGFR ligands, either singly or in combination, while cetuximab activity was largely abrogated under these conditions. We confirmed this finding both in vitro and in vivo in a cell line model of autocrine high-affinity ligand expression. Together, these preclinical studies provide rationale for the clinical study of MM-151 and suggest that high-affinity EGFR ligand expression may be a predictive response marker that distinguishes MM-151 from other anti-EGFR therapeutics. Mol Cancer Ther; 14(7); 1625–36. ©2015 AACR.
Three-Dimensional Cell Culture-Based Screening Identifies the Anthelmintic Drug Nitazoxanide as a Candidate for Treatment of Colorectal Cancer
Authors: Senkowski Wojciech , Zhang Xiaonan , Olofsson Maria Hägg , Isacson Ruben , Höglund Urban , Gustafsson Mats , Nygren Peter , Linder Stig , Larsson Rolf , Fryknäs Mårten
Published: April 2015

Because dormant cancer cells in hypoxic and nutrient-deprived regions of solid tumors provide a major obstacle to treatment, compounds targeting those cells might have clinical benefits. Here, we describe a high-throughput drug screening approach, using glucose-deprived multicellular tumor spheroids (MCTS) with inner hypoxia, to identify compounds that specifically target this cell population. We used a concept of drug repositioning—using known molecules for new indications. This is a promising strategy to identify molecules for rapid clinical advancement. By screening 1,600 compounds with documented clinical history, we aimed to identify candidates with unforeseen potential for repositioning as anticancer drugs. Our screen identified five molecules with pronounced MCTS-selective activity: nitazoxanide, niclosamide, closantel, pyrvinium pamoate, and salinomycin. Herein, we show that all five compounds inhibit mitochondrial respiration. This suggests that cancer cells in low glucose concentrations depend on oxidative phosphorylation rather than solely glycolysis. Importantly, continuous exposure to the compounds was required to achieve effective treatment. Nitazoxanide, an FDA-approved antiprotozoal drug with excellent pharmacokinetic and safety profile, is the only molecule among the screening hits that reaches high plasma concentrations persisting for up to a few hours after single oral dose. Nitazoxanide activated the AMPK pathway and downregulated c-Myc, mTOR, and Wnt signaling at clinically achievable concentrations. Nitazoxanide combined with the cytotoxic drug irinotecan showed anticancer activity in vivo. We here report that the FDA-approved anthelmintic drug nitazoxanide could be a potential candidate for advancement into cancer clinical trials. Mol Cancer Ther; 14(6); 1504–16. ©2015 AACR.
Diaphragm Pacing without Tracheostomy in Congenital Central Hypoventilation Syndrome Patients
Authors: Diep Bonnie , Wang Annie , Kun Sheila , McComb J. Gordon , Shaul Donald B. , Shin Cathy E. , Keens Thomas G. , Perez Iris A.
Published: April 2015

Background: Congenital central hypoventilation syndrome (CCHS) is a rare disorder affecting central control of breathing. Thus, patients require lifelong assisted ventilation. Diaphragm pacing (DP) may permit decannulation in those who are ventilator dependent only during sleep. Objective: The purpose of this study is to determine if patients with CCHS can be successfully ventilated by DP without tracheostomy. Methods: We reviewed the records of 18 CCHS patients (mean age 19.5 ± 10.1 years; 44% female) who were ventilated by DP only during sleep. Results: Prior to diaphragm pacer implantation surgery, 14 CCHS patients had been using home portable positive pressure ventilation (PPV) via tracheostomy, 1 had been on PPV via endotracheal tube, and 3 had been using noninvasive PPV (NPPV). Of the patients with tracheostomy prior to DP (n = 15), 11 (73%) were decannulated and ventilated successfully by DP without tracheostomy. Of all the patients reviewed (n = 18), 13 (72%) were successfully ventilated by DP without tracheostomy. Obesity prevented successful DP without tracheostomy in 1 patient, and upper airway obstruction prevented success in another patient. Snoring and/or obstructive apneas were present in some patients, but they were improved by diaphragm pacer changes, adenotonsillectomy, and/or use of nasal steroids. Conclusions: DP without tracheostomy can be successfully achieved in patients with CCHS. Snoring and obstructive apneas, when present, can be managed by diaphragm pacer changes and medical therapies. Obesity can pose a challenge to successful DP.
The Influence of Known Genetic Variants on Subclinical Cardiovascular Outcomes in Childhood
Authors: Punwasi Rani V.G. , Monnereau Claire , Hofman Albert , Jaddoe Vincent W.V. , Felix Janine F.
Published: April 2015

Background—

Genome-wide association studies have identified single-nucleotide polymorphisms (SNPs) for subclinical cardiovascular outcomes in adults. We examined the influence of these variants on the same outcomes in childhood.

Methods and Results—

In a population-based prospective cohort study among 4137 children, we examined the associations of SNPs, individually and incorporated in genetic risk scores, which were identified in adults for cardiac (2 SNPs for left ventricular end-diastolic diameter and 5 SNPs for aortic root diameter) and blood pressure outcomes (29 SNPs for systolic and diastolic blood pressure, 22 SNPs for mean arterial pressure, and 10 SNPs for pulse pressure) with the same outcomes in children (median age of 6.0 years [95% range, 4.5–8.7]). Weighted and unweighted risk scores for aortic root diameter were associated with childhood aortic root diameter (difference per additional average risk allele 0.09 mm [95% CI: 0.05, 0.13]). Weighted and unweighted risk scores for pulse pressure were associated with childhood pulse pressure (difference per additional average risk allele 0.22 mm Hg [95% CI: 0.08, 0.35] and 0.18 mm Hg [95% CI: 0.05, 0.31], respectively), but not with childhood systolic or diastolic blood pressure or mean arterial pressure. The risk scores for blood pressure and mean arterial pressure were not associated with any of the childhood blood pressure outcomes.

Conclusions—

Genetic risk scores based on SNPs for aortic root diameter and pulse pressure in adults are associated with the same outcomes in children. SNPs related to cardiovascular outcomes in adulthood at least partly influence cardiovascular development from early life onwards.
Clinical Impact of Gastrointestinal Bleeding in Patients Undergoing Percutaneous Coronary Interventions
Authors: Koskinas Konstantinos C. , Räber Lorenz , Zanchin Thomas , Wenaweser Peter , Stortecky Stefan , Moschovitis Aris , Khattab Ahmed A. , Pilgrim Thomas , Blöchlinger Stefan , Moro Christina , Jüni Peter , Meier Bernhard , Heg Dik , Windecker Stephan
Published: April 2015

Background—

The risk factors and clinical sequelae of gastrointestinal bleeding (GIB) in the current era of drug-eluting stents, prolonged dual antiplatelet therapy, and potent P2Y
12
inhibitors are not well established. We determined the frequency, predictors, and clinical impact of GIB after percutaneous coronary interventions (PCIs) in a contemporary cohort of consecutive patients treated with unrestricted use of drug-eluting stents.

Methods and Results—

Between 2009 and 2012, all consecutive patients undergoing PCI were prospectively included in the Bern PCI Registry. Bleeding Academic Research Consortium (BARC) GIB and cardiovascular outcomes were recorded within 1 year of follow-up. Among 6212 patients, 84.1% received new-generation drug-eluting stents and 19.5% received prasugrel. At 1 year, GIB had occurred in 65 patients (1.04%); 70.8% of all events and 84.4% of BARC ≥3B events were recorded >30 days after PCI. The majority of events (64.4%) were related to upper GIB with a more delayed time course compared with lower GIB. Increasing age, previous GIB, history of malignancy, smoking, and triple antithrombotic therapy (ie, oral anticoagulation plus dual antiplatelet therapy) were independent predictors of GIB in multivariable analysis. GIB was associated with increased all-cause mortality (adjusted hazard ratio, 3.40; 95% confidence interval, 1.67–6.92;
P
=0.001) and the composite of death, myocardial infarction, or stroke (adjusted hazard ratio, 3.75; 95% confidence interval, 1.99–7.07;
P
<0.001) and was an independent predictor of all-cause mortality during 1 year.

Conclusions—

Among unselected patients undergoing PCI, GIB has a profound effect on prognosis. Triple antithrombotic therapy emerged as the single drug-related predictor of GIB in addition to patient-related risk factors within 1 year of PCI.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT02241291.
Reperfusion Times for Radial Versus Femoral Access in Patients With ST-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention
Authors: Cantor Warren J. , Ko Dennis T. , Natarajan Madhu K. , Džavík Vladimír , Wijeysundera Harindra C. , Wang Julie T. , Kingsbury Kori J. , Velianou James L. , Cohen Eric A. , Le May Michel R. , Tu Jack V.
Published: April 2015

Background—

Radial access is associated with less bleeding and vascular complications. However, it may delay reperfusion during primary percutaneous coronary intervention for ST-segment–elevation myocardial infarction.

Methods and Results—

A provincial database prospectively collected clinical and procedural characteristics for all urgent percutaneous coronary intervention procedures performed between June 2010 and September 2011 in Ontario for ST-segment–elevation myocardial infarction, including time of arrival in the catheterization laboratory and time of first balloon inflation. After excluding patients with cardiogenic shock, with previous bypass surgery, or who received fibrinolysis, 2947 patients were included in the analysis. Propensity score matching was used to minimize difference in clinical characteristics between radial and femoral access procedures. Predictors of radial access included younger age and male sex. After propensity score matching, the median time from arrival in the cardiac catheterization laboratory to first balloon was 27 minutes (25th%–75th%, 21–34) for the femoral group and 30 minutes (25th%–75th %, 24–39) for the radial group (
P
<0.001). When hospitals were stratified based on the proportion of primary percutaneous coronary intervention cases that were performed using radial access, there was no difference in treatment times between radial and femoral access in the tercile of hospitals that used radial access most frequently. There were no significant differences in the rates of death or myocardial infarction at 30 days.

Conclusions—

This contemporary multicenter registry demonstrates that the time to first balloon inflation is slightly longer with radial access than with femoral access, although the 3 minute difference is unlikely to be clinically relevant. There is no difference in treatment times at hospitals that frequently use radial access for primary percutaneous coronary intervention. Short-term mortality and reinfarction rates are similar with radial and femoral access.
Mass Screening for Untreated Atrial Fibrillation
Authors: Svennberg Emma , Engdahl Johan , Al-Khalili Faris , Friberg Leif , Frykman Viveka , Rosenqvist Mårten
Published: April 2015

Background—

The aims of the present study were to define the prevalence of untreated atrial fibrillation (AF) in a systematic screening program using intermittent ECG recordings among 75- to 76-year-old individuals and to study the feasibility of initiating protective oral anticoagulant (OAC) treatment.

Methods and Results—

Half of the 75- to 76-year-old population in 2 Swedish regions were invited to a screening program for AF. Participants without a previous diagnosis of AF underwent intermittent ECG recordings over 2 weeks. If AF was detected, participants were offered OAC. During the 28-month inclusion period, 13 331 inhabitants were invited. Of these, 7173 (53.8%) participated. Of the participants, 218 (3.0%; 95% confidence interval [CI], 2.7–3.5) were found to have previously unknown AF, and of these, AF was found in 37 (0.5% of the screened population) on their first ECG. The use of intermittent ECGs increased new AF detection 4-fold. A previous diagnosis of AF was known in 9.3% (n=666; 95% CI, 8.6–10.0). Total AF prevalence in the screened population was 12.3%. Of participants with known AF, 149 (2.1%; 95% CI, 1.8–2.4) had no OAC treatment. In total, 5.1% (95% CI, 4.6–5.7) of the screened population had untreated AF; screening resulted in initiation of OAC treatment in 3.7% (95% CI, 3.3–4.2) of the screened population. More than 90% of the participants with previously undiagnosed AF accepted initiation of OAC treatment.

Conclusions—

Mass screening for AF in a 75- to 76-year-old population identifies a significant proportion of participants with untreated AF. Initiation of stroke prophylactic treatment was highly successful in individuals with newly diagnosed AF.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01593553.
Accumulation of Metabolic Cardiovascular Risk Factors in Black and White Young Adults Over 20 Years
Authors: Paynter Nina P. , Kiefe Catarina I. , Lewis Cora E. , Loria Catherine M. , Goff David C. , Lloyd‐Jones Donald M.
Published: April 2015

Background

Cross‐sectional clustering of metabolic risk factors for cardiovascular disease in middle‐aged adults is well described, but less is known regarding the order in which risk factors develop through young adulthood and their relation to subclinical atherosclerosis.

Method and Results

A total of 3178 black and white women and men in the Coronary Artery Risk Development in Young Adults study were assessed to identify the order in which cardiovascular disease risk factors including diabetes, hypertension, dyslipidemia (low high‐density lipoprotein cholesterol or high triglyceride levels), hypercholesterolemia (high total or low‐density lipoprotein cholesterol), and obesity develop. Observed patterns of risk factor development were compared with those expected if risk factors accumulated randomly, given their overall distribution in the population. Over the 20 years of follow‐up, 80% of participants developed at least 1 risk factor. The first factor to occur was dyslipidemia in 39% of participants, obesity in 20%, hypercholesterolemia in 11%, hypertension in 7%, and diabetes in 1%. Dyslipidemia was the only risk factor both to occur first and to be followed by additional risk factors more often than expected (
P
<0.001 for both). Order of risk factor accrual did not affect subclinical atherosclerosis at year 20. Results were similar by sex, race, and smoking status.

Conclusions

Multiple patterns of cardiovascular risk factor development were observed from young adulthood to middle age. Dyslipidemia, a potentially modifiable condition, often preceded the development of other risk factors and may be a useful target for intervention and monitoring.
Increased Interannual Precipitation Extremes over California under Climate Change
Authors: Berg Neil , Hall Alex
Published: April 2015

Changes to mean and extreme wet season precipitation over California on interannual time scales are analyzed using twenty-first-century precipitation data from 34 global climate models. Models disagree on the sign of projected changes in mean precipitation, although in most models the change is very small compared to historical and simulated levels of interannual variability. For the 2020/21–2059/60 period, there is no projected increase in the frequency of extremely dry wet seasons in the ensemble mean. Wet extremes are found to increase to around 2 times the historical frequency, which is statistically significant at the 95% level. Stronger signals emerge in the 2060/61–2099/2100 period. Across all models, extremely dry wet seasons are roughly 1.5 to 2 times more common, and wet extremes generally triple in their historical frequency (statistically significant). Large increases in precipitation variability in most models account for the modest increases to dry extremes. Increases in the frequency of wet extremes can be ascribed to equal contributions from increased variability and increases to the mean. These increases in the frequency of interannual precipitation extremes will create severe water management problems in a region where coping with large interannual variability in precipitation is already a challenge. Evidence from models and observations is examined to understand the causes of the low precipitation associated with the 2013/14 drought in California. These lines of evidence all strongly indicate that the low 2013/14 wet season precipitation total can be very likely attributed to natural variability, in spite of the projected future changes in extremes.
Idiopathic Subglottic and Tracheal Stenosis
Authors: Gnagi Sharon H. , Howard Brittany E. , Anderson Catherine , Lott David G.
Published: April 2015

Objectives:

To report and compare patients’ experiences with acquired subglottic stenosis (AS) versus idiopathic subglottic and tracheal stenosis (ISTS).

Methods:

A survey was made available to patients with AS and ISTS. Results were analyzed for inter- and intragroup differences using a 2-tailed t test.

Results:

The study included 160 survey participants (AS n = 28; ISTS n = 132), with a predominance of female participants (82% AS, 98% ISTS). Acid reflux was the most prevalent comorbidity across groups (42%-43%). A significant difference in time to diagnosis was found between groups, with 32% of AS patients diagnosed within 3 months of symptom onset, compared to 2% with ISTS. A diagnosis delay greater than 18 months occurred for 58% of ISTS patients. There was no difference in treatment approach, with the most common treatment being balloon dilation, followed by laser dilation. Tracheal resection was performed in 36% of patients in both groups. Patient satisfaction with surgical outcomes was significantly higher after tracheal resection (76%) compared to other treatment modalities (39%).

Conclusions:

ISTS remains a diagnostic challenge as highlighted by the delay in diagnosis compared to AS. There appears to be no historical or symptomatic factors specific to ISTS. Additionally, patients report increased satisfaction and symptom resolution after tracheal resection.
Gentle blood aspiration and tube cushioning reduce pneumatic tube system interference in lactate dehydrogenase assays
Authors: Strubi-Vuillaume Isabelle , Carlier Valentine , Obeuf Catherine , Vasseur Francis , Maury J-Claude , Maboudou Patrice , Mangalaboyi Jacques , Durocher Alain , Launay David , Noel Christian , Brousseau Thierry
Published: April 2015

Background

Use of a hospital pneumatic tube system may be associated with measurement errors.

Methods

A venous blood sample was collected from 79 patients into a pair of lithium heparin tubes; one tube was sent to the laboratory by porter and the other was sent via the pneumatic tube system. Plasma lactate dehydrogenase concentrations were then assayed.

Results

Lactate dehydrogenase concentrations were overestimated (median bias: 18.8%) when evacuated vacuum lithium heparin tubes were sent by pneumatic tube system. This bias was reduced by bubble-wrapping the standard lithium heparin tube or using Monovette lithium heparin tubes in aspiration mode (median bias: +8.7% and −0.3%, respectively).

Conclusions

Cushioning and aspiration-mode sampling may limit pneumatic tube system-associated overestimation of lactate dehydrogenase concentrations.
Followers of the Dao of the Bible
Authors: Marshall Alison R.
Published: April 2015

Studies of pre-1950s Chinese Canadian Christianity have tended to occlude Chinese perspectives and experiences for a number of reasons, including a lack of sources. Drawing on largely unpublished Chinese and English source materials including scrapbooks, correspondence, reports, membership rosters, marriage, funeral and clergy records, Chinese nationalist registers, diaries, oral histories, photographs and material culture, this article investigates Chinese experiences of Canadian Presbyterian missionary work in Victoria, Cumberland, Calgary, Winnipeg, Toronto and Montreal between 1896 and 1950. By examining the personal archival materials of Ma Seung, Frank Chan and Ernest Mark, and era-specific Chinese political involvements and fieldwork data, this article challenges previous simplistic understandings of the Chinese missionary experience that were based solely on the perspectives of mainstream Christian institutions and society. This article emphasizes the Chinese context and concepts such as the dao, efficacy ( ling), and affect ( renqing, or human sentiments) that guided relationships and faith in early Chinese Canada. It aims to provide a more complicated understanding of why Chinese ministers chose to Christianize fellow Chinese, and why before 1950 many Chinese chose to be nominal Christians and only a small number converted.
Black Feminist-Womanist Research Paradigm
Authors: Lindsay-Dennis LaShawnda
Published: April 2015

Black Feminist and Womanist theories are culturally based perspectives that take into consideration the contextual and interactive effects of herstory culture, race, class, gender, and other forms of oppression. These frameworks provide a contextualized understanding of African American girls’ experiences and perspectives. The purpose of this article is to provide an overview of the current status of research about African American girls. In addition, this article demonstrates the need for a theoretical perspective that can be used to produce research that accurately examines the lives of African American girls. Major themes of Black Feminist Thought and Womanism will serve as a viable theoretical framework for studying this population. Last, principles of a Black Feminist-Womanist research model will be defined.
Correlates of Psychosocial Development for Taiwanese Youth
Authors: Beckert Troy E. , Lee Chien-Ti , Ota Carrie L.
Published: April 2015

The purpose of this study was to assess the effect of parenting behavior, friendship support, collective value affiliation, and gender on psychosocial development with a sample of youth from urban and rural areas from Taiwan ( N = 787). We first applied latent profile analysis (LPA) to identify patterns of psychosocial outcomes. Next, a series of pairwise equality tests and logistic regression revealed the individual and unique effect of each predictor. We identified two patterns of psychosocial outcomes and observed significant associations between predictors and psychosocial development based on class membership. These results suggest that among all predictors, parenting satisfaction and friendship support were particularly predictive in an enhanced psychosocial development status.
Candidate Gene Analyses of Skeletal Variation in Malocclusion
Authors: da Fontoura C.S.G. , Miller S.F. , Wehby G.L. , Amendt B.A. , Holton N.E. , Southard T.E. , Allareddy V. , Moreno Uribe L.M.
Published: April 2015

This study evaluated associations between craniofacial candidate genes and skeletal variation in patients with malocclusion. Lateral cephalometric radiographs of 269 untreated adults with skeletal classes I, II, and III malocclusion were digitized with 14 landmarks. Two-dimensional coordinates were analyzed using Procrustes fit and principal component (PC) analysis to generate continuous malocclusion phenotypes. Skeletal class classifications (I, II, or III) were used as a categorical phenotype. Individuals were genotyped for 198 single-nucleotide polymorphisms (SNPs) in 71 craniofacial genes and loci. Phenotype-genotype associations were tested via multivariate linear regression for continuous phenotypes and multinomial logistic regression for skeletal malocclusion class. PC analysis resulted in 4 principal components (PCs) explaining 69% of the total skeletal facial variation. PC1 explained 32.7% of the variation and depicted vertical discrepancies ranging from skeletal deep to open bites. PC1 was associated with a SNP near PAX5 ( P = 0.01). PC2 explained 21.7% and captured horizontal maxillomandibular discrepancies. PC2 was associated with SNPs upstream of SNAI3 ( P = 0.0002) and MYO1H ( P = 0.006). PC3 explained 8.2% and captured variation in ramus height, body length, and anterior cranial base orientation. PC3 was associated with TWIST1 ( P = 0.000076). Finally, PC4 explained 6.6% and detected variation in condylar inclination as well as symphysis projection. PC4 was associated with PAX7 ( P = 0.007). Furthermore, skeletal class II risk increased relative to class I with the minor alleles of SNPs in FGFR2 (odds ratio [OR] = 2.1, P = 0.004) and declined with SNPs in EDN1 (OR = 0.5, P = 0.007). Conversely, skeletal class III risk increased versus class I with SNPs in FGFR2 (OR 2.2, P = 0.005) and COL1A1 (OR = 2.1, P = 0.008) and declined with SNPs in TBX5 (OR = 0.5, P = 0.014). PAX5, SNAI3, MYO1H, TWIST1, and PAX7 are associated with craniofacial skeletal variation among patients with malocclusion, while FGFR2, EDN1, TBX5, and COL1A1 are associated with type of skeletal malocclusion.
The Gene Network Underlying Hypodontia
Authors: Yin W. , Bian Z.
Published: April 2015

Mammalian tooth development is a precise and complicated procedure. Several signaling pathways, such as nuclear factor (NF)–κB and WNT, are key regulators of tooth development. Any disturbance of these signaling pathways can potentially affect or block normal tooth development, and presently, there are more than 150 syndromes and 80 genes known to be related to tooth agenesis. Clarifying the interaction and crosstalk among these genes will provide important information regarding the mechanisms underlying missing teeth. In the current review, we summarize recently published findings on genes related to isolated and syndromic tooth agenesis; most of these genes function as positive regulators of cell proliferation or negative regulators of cell differentiation and apoptosis. Furthermore, we explore the corresponding networks involving these genes in addition to their implications for the clinical management of tooth agenesis. We conclude that this requires further study to improve patients’ quality of life in the future.
Longitudinal Associations among Discordant Sexual Orientation Dimensions and Hazardous Drinking in a Cohort of Sexual Minority Women
Authors: Talley Amelia E. , Aranda Frances , Hughes Tonda L. , Everett Bethany , Johnson Timothy P.
Published: April 2015

We examined differences between sexual minority women’s (SMW’s) sexual identity and sexual behavior or sexual attraction as potential contributors to hazardous drinking across a 10-year period. Data are from a longitudinal study examining drinking and drinking-related problems in a diverse, community-based sample of self-identified SMW (Wave 1: n = 447; Wave 2: n = 384; Wave 3: n = 354). Longitudinal cross-lagged models showed that SMW who report higher levels of identity-behavior or identity-attraction discordance may be at greater risk of concurrent and subsequent hazardous drinking. Results of multigroup models suggest that sexual orientation discordance is a more potent risk factor for risky drinking outcomes among SMW in older adulthood than in younger adulthood. Findings support that discordance between sexual orientation dimensions may contribute to hazardous drinking among SMW and provide evidence that cognitive-behavioral consistency is important for individuals expressing diverse and fluid sexual identities, attraction, and behavior.
The global union federations in international industrial relations: A critical review
Authors: Ford Michele , Gillan Michael
Published: April 2015

In recent decades, trade unions have been challenged to develop new forms of representation, action and institutional engagement in response to the increasingly transnational character of production and service delivery. This has necessarily required a shift in focus beyond national boundaries, and thus beyond the traditional scale of industrial relations systems. Among the most important actors in these attempts to globalize industrial relations have been the global union federations (GUFs), which represent national sectoral federations in key industries. Over several decades, the GUFs have sought to engage with multinational corporations through various strategies including policy campaigns and the negotiation of Global Framework Agreements (GFAs) and have provided support for workers and their unions in different national settings, including emerging labour movements in the Global South. This article reviews the growing literature on transnational industrial relations, focusing on the historical development of the GUFs, their core repertoires of action and their impact on industrial relations practice both internationally and within national boundaries. In doing so, it identifies and assesses not only the opportunities for GUF interventions in international industrial relations, but also the many obstacles – including resource constraints and dependence on unions at other scales – that limit their reach and ability to achieve these strategic goals.
Gillick, bone marrow and teenagers
Authors: Cherkassky Lisa
Published: April 2015

The Human Tissue Authority can authorise a bone marrow harvest on a child of any age if a person with parental responsibility consents to the procedure. Older children have the legal capacity to consent to medical procedures under Gillick, but it is unclear if Gillick can be applied to non-therapeutic medical procedures. The relevant donation guidelines state that the High Court shall be consulted in the event of a disagreement, but what is in the best interests of the teenage donor under s.1 of the Children Act 1989? There are no legal authorities on child bone marrow harvests in the United Kingdom. This article considers the best interests of the older saviour sibling and questions whether, for the purposes of welfare, the speculative benefits could outweigh the physical burdens.
Dynamically reconfigurable command and control structure for network-centric warfare
Authors: Pang Chee Khiang , Mathew Josey
Published: April 2015

The rapidly changing battle conditions in modern network-centric operations prescribe expectations for speedy deployment and nimble ad hoc reconfiguration of military networked teams. In this paper, a formal command and control (C2) structure is presented that allows for reliable ad hoc reconfiguration of tasks and resources of multiple simultaneous missions. Missions and assigned resources can be removed or added in an online manner without affecting other running missions. A mathematically justified software tool called the Reconfigurable Discrete Event Control (RDEC) is proposed by extending an existing framework using simple matrix decomposition. The RDEC effectively allows multiple fighting platforms of different interdisciplinary fields to join and leave the network easily in a “plug-and-play” manner. The proposed C2 structure is developed and demonstrated on a simulation study involving a Singapore armed forces team with three realistic attack missions. Extensive simulation results verify that the networked team is fairly sequenced and the missions and resources can be removed or added without blocking effects.
Development and Psychometric Assessment of the Healthcare Provider Cultural Competence Instrument
Authors: Schwarz Joshua L. , Witte Raymond , Sellers Sherrill L. , Luzadis Rebecca A. , Weiner Judith L. , Domingo-Snyder Eloiza , Page James E.
Published: April 2015

This study presents the measurement properties of 5 scales used in the Healthcare Provider Cultural Competence Instrument (HPCCI). The HPCCI measures a health care provider’s cultural competence along 5 primary dimensions: (1) awareness/sensitivity, (2) behaviors, (3) patient-centered communication, (4) practice orientation, and (5) self-assessment. Exploratory factor analysis demonstrated that the 5 scales were distinct, and within each scale items loaded as expected. Reliability statistics indicated a high level of internal consistency within each scale. The results indicate that the HPCCI effectively measures the cultural competence of health care providers and can provide useful professional feedback for practitioners and organizations seeking to increase a practitioner’s cultural competence.
Five women’s recollections and reflections on being raised by a mother with psychosis
Authors: Kadish Yael
Published: April 2015

This qualitative research project explored the recollections and reflections of women who were raised by mothers suffering with psychosis. Existing research has documented the mostly negative effects of maternal psychopathology on offspring; they are exposed to both the genetic and environmental effects of such illness. Very few qualitative studies exist in this research area. The mother–daughter perspective was taken to explore the ways that daughters felt maternal psychosis might have affected this primary relationship. Five participants comprised the purposive, snowball sample. The semi-structured interview method was used for data collection. The data was analysed using thematic content analysis. Nine themes and two sub-themes emerged from the interview data; these were (1) resilience and survival (with two sub-themes: (1.1) extreme self-sufficiency and (1.2) low self-esteem and the need for approval); (2) memories of maternal psychotic episodes; (3) mother–daughter bond; (4) importance of father; (5) sibling sounding boards and responsibilities; (6) silent family storms; (7) significant others; (8) stigma, shame, and secrecy; and (9) maternal psychosis, motherhood, and feminine identity. All participants believe that maternal psychosis had affected them profoundly, both in childhood and adulthood. They felt that it had influenced their personality development in various ways, including the formation of feminine identity.
From Trash to Treasure
Authors: Lu Di Yin
Published: April 2015

Since 1951, salvage archaeologists in the People’s Republic of China (PRC) have retrieved tons of ancient artifacts from municipal scrapyards, refineries, and industrial development sites. They evaluated the artifacts for quality and distributed them to Chinese museums, libraries, hotels, restaurants, and art dealerships, which promoted the objects as representative of China’s ancient past. This article examines the salvage archaeology program in Shanghai, one of the largest in the country. Shanghai evaluated metal and paper scrap from collecting stations throughout China. Salvage archaeologists in this program benefited from movements such as the Great Leap Forward (1958–1961) and the Cultural Revolution (1966–1976), as these movements allowed them to collect unprecedented quantities of ancient coins, standard weights and measures, weapons, agricultural implements, and ethnic minority artifacts. The program created museum and library collections across the PRC, and changed the distribution of bronze artifacts both in China and overseas. Covering the history of salvage archaeology in Shanghai over four decades, this article argues that “trash picking” increased the availability and visibility of bronze and textual artifacts throughout the PRC. It further argues that salvage archaeology shaped what Chinese people regard as relics of Chinese civilization.
Using High-Level Construal and Perceptions of Changeability to Promote Self-Change Over Self-Protection Motives in Response to Negative Feedback
Authors: Belding Jennifer N. , Naufel Karen Z. , Fujita Kentaro
Published: April 2015

Diagnostic negative information presents people with a motivational dilemma. Although negative feedback can provide useful information with which to guide future self-improvement efforts, it also presents short-term affective costs. We propose that construal level, jointly with the perceived changeability of the feedback domain, determines whether people choose to accept or dismiss such information. Whereas low-level construal promotes short-term self-protection motivation (promoting dismissal), high-level construal promotes long-term self-change motivation (promoting acceptance)—to the extent that change is perceived as possible. Four studies support this hypothesis and examine underlying cognitive and motivational mechanisms. The present work may provide an integrative theoretical framework for understanding when people will be open to and accept negative diagnostic information, and has important practical implications for promoting self-change efforts.
Barriers in seeking health information from primary healthcare facilities in Pakistan
Authors: Naeem Salman Bin , Bhatti Rubina
Published: April 2015

Primary care physicians (PCPs) need a wide range of health information resources to manage their patients. The present study aimed to investigate the barriers that obstruct the health information seeking behavior of primary care physicians in Pakistan from their practice setting. A survey was carried out in 77 basic health units (BHUs), seven rural health centers (RHCs), and two tehsil headquarters (THQs) of Multan District, Pakistan. A three-part questionnaire containing participants’ demographic information, barriers in seeking health information, and required sources and services, was distributed to primary care physicians through post, email, and personal visits to participating healthcare facilities. The data was analyzed statistically using SPSS. Chi square and Kruskal Wallis tests were applied to determine if there were any significant differences in demographic information of different healthcare facilities participants, the barriers they faced in seeking health information, and the required sources and services available to them. The major barriers included: no onsite library, no health sciences librarian, scarcity of health information resources, inaccessibility of health information system, and lack of information and technological infrastructure. Consultation with seniors, improved connectivity and document delivery services were among the sources and services most required by primary care physicians. The study concluded that primary care physicians encounter multiple barriers that obstruct their health-related information seeking behavior, which compromises patient care. Medical librarians should design outreach library and information services in health sciences and health information literacy programs to overcome the barriers primary care physicians face while seeking health information from their practice settings.
Extracorporeal membrane oxygenation in acute massive pulmonary embolism: a systematic review
Authors: Yusuff HO , Zochios V , Vuylsteke A
Published: April 2015

Massive pulmonary embolism (PE) can present with extreme physiological dysfunction, characterised by acute right ventricular failure, hypoxaemia unresponsive to conventional therapy and cardiac arrest. Consensus regarding the management of patients with persistent shock following thrombolysis is lacking. Our primary objective was to describe the application of extracorporeal membrane oxygenation (ECMO) in the treatment of acute massive PE. We were unable to identify any randomised controlled trials (RCTs) comparing ECMO with other support systems in the setting of massive PE. We reviewed case reports and case series published in the past 20 years to evaluate the mortality rate and any poor prognostic factors. Overall survival was 70.1% and none of the definitive treatment modalities was associated with a higher mortality (thrombolysis - OR - 0.99, P - 0.9, catheter embolectomy - OR - 1.01, P - 0.99, surgical embolectomy - OR - 0.44, P - 0.20). Patients who had ECMO instituted whilst in cardiorespiratory arrest had a higher risk of death. (OR - 16.71, P - 0.0004). When compared with other causes of cardiac arrest, patients who survived a massive PE presented a good neurological outcome (cerebral performance category 1 or 2).
The Use of Social Media to Foster Trust, Mentorship, and Collaboration in Scientific Organizations
Authors: Murthy Dhiraj , Hastings Calla M. , Mawrie Somya A.
Published: April 2015

Many domains are well known for their resistance to social media. Currently, there is a dearth of literature that explores social media use in these contexts. This study seeks to help address this gap by evaluating the use of social media within a scientific organization (anonymized as SciCity) that has a strong virtual presence and quarterly face-to-face meet-ups. We evaluated SciCity’s use of social media to foster trust, collaboration, and mentorship. We found that the prominent social media platform Twitter fosters trust among organizational members and plays a role in creating and maintaining lightweight collaborative relationships. Additionally, Twitter-based relationships often act as precursors to collaborations that occur face-to-face. However, Twitter, by itself, was not found to be successful in promoting formal collaborations. Though the medium did facilitate sporadic mentoring, supplementary non-social media-based communication was needed to form mentorship relationships. Twitter was also found to serve as a “social lubricant,” making contact easier and faster, thereby helping foster a scientific social network. Though minor in its role in specifically fostering scientific collaboration, the use of social media by SciCity indicates a shift toward acceptable uses of social media for scientific organizations that have traditionally been hesitant to use social media.
Same- and Other-Sex Popularity and Preference During Early Adolescence
Authors: Bowker Julie C. , Adams Ryan E. , Bowker Matthew H. , Fisher Carrie , Spencer Sarah V.
Published: April 2015

This study examined the longitudinal and bidirectional relations between same-sex (SS) and other-sex (OS) popularity and preference across one school year. Participants were 271 sixth-grade students who completed peer nomination measures at three time points in their schools. Tests of cross-lagged autoregressive models indicated that SS popularity predicted later OS popularity and vice versa. OS preference predicted later SS preference but not vice versa. Findings highlight the importance of more carefully considering the distinctions and associations between SS and OS popularity and preference during early adolescence while setting the stage for future group-level peer relations research.
Using Dual Beta Distributions to Create “Proper” ROC Curves Based on Rating Category Data
Authors: Mossman Douglas , Peng Hongying
Published: April 2015

Background: Receiver operating characteristic (ROC) analysis helps investigators quantify and describe how well a diagnostic system discriminates between 2 mutually exclusive conditions. The conventional binormal (CvB) curve-fitting model usually produces ROCs that are improper in that they do not have the ever-decreasing slope required by signal detection theory. When data sets evaluated under the CvB model have hooks, the resulting ROCs can contain misleading information about the diagnostic performance of the method at low and high false positive rates. Objective: To present and evaluate a dual beta (DB) ROC model that assumes diagnostic data arise from 2 β distributions. The DB model’s parameter constraints assure that the resulting ROC curve has a positive, monotonically decreasing slope. Design/Method: Computer simulation study comparing results from CvB, DB, and weighted power function (WPF) models. Results: The DB model produces results that are as good as or better than those from the WPF model, and less biased and closer to the true values than curves obtained using the CvB model. Conclusions: The DB ROC model expresses the relationship between the false positive rate and true positive rate in closed form and allows for quick ROC area calculations using spreadsheet functions. Because it posits simple relationships among the decision axis, operating points, and model parameters, the DB model offers investigators a flexible, easy-to-grasp ROC form that is simpler to implement than other proper ROC models.
An Efficient Estimator for the Expected Value of Sample Information
Authors: Menzies Nicolas A.
Published: April 2015

Background. Conventional estimators for the expected value of sample information (EVSI) are computationally expensive or limited to specific analytic scenarios. I describe a novel approach that allows efficient EVSI computation for a wide range of study designs and is applicable to models of arbitrary complexity. Methods.The posterior parameter distribution produced by a hypothetical study is estimated by reweighting existing draws from the prior distribution. EVSI can then be estimated using a conventional probabilistic sensitivity analysis, with no further model evaluations and with a simple sequence of calculations (Algorithm 1). A refinement to this approach (Algorithm 2) uses smoothing techniques to improve accuracy. Algorithm performance was compared with the conventional EVSI estimator (2-level Monte Carlo integration) and an alternative developed by Brennan and Kharroubi (BK), in a cost-effectiveness case study. Results. Compared with the conventional estimator, Algorithm 2 exhibited a root mean square error (RMSE) 8%–17% lower, with far fewer model evaluations (3–4 orders of magnitude). Algorithm 1 produced results similar to those of the conventional estimator when study evidence was weak but underestimated EVSI when study evidence was strong. Compared with the BK estimator, the proposed algorithms reduced RSME by 18%–38% in most analytic scenarios, with 40 times fewer model evaluations. Algorithm 1 performed poorly in the context of strong study evidence. All methods were sensitive to the number of samples in the outer loop of the simulation. Conclusions. The proposed algorithms remove two major challenges for estimating EVSI—the difficulty of estimating the posterior parameter distribution given hypothetical study data and the need for many model evaluations to obtain stable and unbiased results. These approaches make EVSI estimation feasible for a wide range of analytic scenarios.