bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel EGFR Isoform Confers Increased Invasiveness to Cancer Cells
Authors: Zhou Min , Wang Hai , Zhou Keke , Luo Xiaoying , Pan Xiaorong , Shi Bizhi , Jiang Hua , Zhang Jiqin , Li Kesang , Wang Hua-Mao , Gao Huiping , Lu Shun , Yao Ming , Mao Ying , Wang Hong-Yang , Yang Shengli , Gu Jianren , Li Chuanyuan , Li Zonghai
Published: November 2013

As a validated therapeutic target in several human cancers, the EGF receptor (EGFR) provides a focus to gain deeper insights into cancer pathophysiology. In this study, we report the identification of a naturally occurring and widely expressed EGFR isoform termed EGFRvA, which substitutes a Ser/Thr-rich peptide for part of the carboxyl-terminal regulatory domain of the receptor. Intriguingly, EGFRvA expression relates more closely to histopathologic grade and poor prognosis in patients with glioma. Ectopic expression of EGFRvA in cancer cells conferred a higher invasive capacity than EGFR in vitro and in vivo. Mechanistically, EGFRvA stimulated expression of STAT3, which upregulated heparin-binding EGF (HB-EGF). Reciprocally, HB-EGF stimulated phosphorylation of EGFRvA at Y845 along with STAT3, generating a positive feedback loop that may reinforce invasive function. The significance of EGFRvA expression was reinforced by findings that it is attenuated by miR-542-5p, a microRNA that is a known tumor suppressor. Taken together, our findings define this newfound EGFR isoform as a key theranostic molecule. Cancer Res; 73(23); 7056–67. ©2013 AACR.
Targeting Small Cell Lung Cancer Harboring PIK3CA Mutation with a Selective Oral PI3K Inhibitor PF-4989216
Authors: Walls Marlena , Baxi Sangita M. , Mehta Pramod P. , Liu Kevin K.-C. , Zhu JinJiang , Estrella Heather , Li Chunze , Zientek Michael , Zong Qing , Smeal Tod , Yin Min-Jean
Published: November 2013

Purpose: Constitutive activation of phosphoinositide 3-kinase (PI3K) occurs frequently in many human tumors via either gene mutation in the p110α catalytic subunit of PI3K or functional loss of tumor suppressor PTEN. Patients with small-cell lung cancer (SCLC) have very poor prognosis and survival rates such that an effective targeted therapy is in strong demand for these patients. In this study, we characterized the highly selective oral PI3K inhibitor, PF-4989216, in preclinical SCLC models to investigate whether targeting the PI3K pathway is an effective targeted therapy option for SCLCs that harbor a PIK3CA mutation.

Experimental Design: A panel of SCLC cell lines with PIK3CA mutation or PTEN loss were treated with PF-4989216 in several in vitro assays, including PI3K pathway signaling, cell viability, apoptosis, cell-cycle progression, and cell transformation. SCLC cell lines that were sensitive in vitro to PF-4989216 were further evaluated by in vivo animal studies to determine the pharmacokinetic/pharmacodynamic relationship and tumor growth inhibition (TGI) by PF-4989216 treatment.

Results: PF-4989216 inhibited PI3K downstream signaling and subsequently led to apoptosis induction, and inhibition in cell viability, transformation, and xenograft tumor growth in SCLCs harboring PIK3CA mutation. In SCLCs with PTEN loss, PF-4989216 also inhibited PI3K signaling but did not induce BCL2-interacting mediator (BIM)-mediated apoptosis nor was there any effect on cell viability or transformation. These results implicate differential tumorigenesis and apoptosis mechanisms in SCLCs harboring PIK3CA mutation versus PTEN loss.

Conclusions: Our results suggest that PF-4989216 is a potential cancer drug candidate for patients with SCLC with PIK3CA mutation but not PTEN loss. Clin Cancer Res; 20(3); 631–43. ©2013 AACR.
IgG-Switched CLL Has a Distinct Immunogenetic Signature from the Common MD Variant: Ontogenetic Implications
Authors: Vardi Anna , Agathangelidis Andreas , Sutton Lesley-Ann , Chatzouli Maria , Scarfò Lydia , Mansouri Larry , Douka Vassiliki , Anagnostopoulos Achilles , Darzentas Nikos , Rosenquist Richard , Ghia Paolo , Belessi Chrysoula , Stamatopoulos Kostas
Published: November 2013

Purpose: Immunoglobulin G–switched chronic lymphocytic leukemia (G-CLL) is a rare variant of CLL, whose origin and ontogenetic relationship to the common IgM/IgD (MD-CLL) variant remains undefined. Here, we sought for clues about the ontogeny of G-CLL versus MD-CLL by profiling the relevant IG gene repertoires.

Experimental Design: Using purpose-built bioinformatics methods, we performed detailed immunogenetic profiling of a multinational CLL cohort comprising 1,256 cases, of which 1,087 and 169 expressed IG mu/delta and gamma heavy chains, respectively.

Results: G-CLL has a highly skewed IG gene repertoire that is distinct from MD-CLL, especially in terms of (i) overuse of the IGHV4-34 and IGHV4-39 genes and (ii) differential somatic hypermutation (SHM) load. Repertoire differences were also found when comparing subgroups with similar SHM status and were mainly attributed to the exclusive representation in G-CLL of two major subsets with quasi-identical (stereotyped) B-cell receptors. These subsets, namely #4 (IGHV4-34/IGKV2-30) and #8 (IGHV4-39/IGKV1(D)-39), were found to display sharply contrasting SHM and clinical behavior.

Conclusions: G-CLL exhibits an overall distinct immunogenetic signature from MD-CLL, prompting speculations about distinct ontogenetic derivation and/or immune triggering. The reasons underlying the differential regulation of SHM among G-CLL cases remain to be elucidated. Clin Cancer Res; 20(2); 323–30. ©2013 AACR.
Tumor Growth Rate Is an Early Indicator of Antitumor Drug Activity in Phase I Clinical Trials
Authors: Ferté Charles , Fernandez Marianna , Hollebecque Antoine , Koscielny Serge , Levy Antonin , Massard Christophe , Balheda Rastislav , Bot Brian , Gomez-Roca Carlos , Dromain Clarisse , Ammari Samy , Soria Jean-Charles
Published: November 2013

Purpose: Response Evaluation Criteria in Solid Tumors (RECIST) evaluation does not take into account the pretreatment tumor kinetics and may provide incomplete information about experimental drug activity. Tumor growth rate (TGR) allows for a dynamic and quantitative assessment of the tumor kinetics. How TGR varies along the introduction of experimental therapeutics and is associated with outcome in phase I patients remains unknown.

Experimental Design: Medical records from all patients (N = 253) prospectively treated in 20 phase I trials were analyzed. TGR was computed during the pretreatment period (reference) and the experimental period. Associations between TGR, standard prognostic scores [Royal Marsden Hospital (RMH) score], and outcome [progression-free survival (PFS) and overall survival (OS)] were computed (multivariate analysis).

Results: We observed a reduction of TGR between the reference versus experimental periods (38% vs. 4.4%; P < 0.00001). Although most patients were classified as stable disease (65%) or progressive disease (25%) by RECIST at the first evaluation, 82% and 65% of them exhibited a decrease in TGR, respectively. In a multivariate analysis, only the decrease of TGR was associated with PFS (P = 0.004), whereas the RMH score was the only variable associated with OS (P = 0.0008). Only the investigated regimens delivered were associated with a decrease of TGR (P < 0.00001, multivariate analysis). Computing TGR profiles across different clinical trials reveals specific patterns of antitumor activity.

Conclusions: Exploring TGR in phase I patients is simple and provides clinically relevant information: (i) an early and subtle assessment of signs of antitumor activity; (ii) independent association with PFS; and (iii) it reveals drug-specific profiles, suggesting potential utility for guiding the further development of the investigational drugs. Clin Cancer Res; 20(1); 246–52. ©2013 AACR.
MUC4-Mediated Regulation of Acute Phase Protein Lipocalin 2 through HER2/AKT/NF-κB Signaling in Pancreatic Cancer
Authors: Kaur Sukhwinder , Sharma Neil , Krishn Shiv Ram , Lakshmanan Imay , Rachagani Satyanarayana , Baine Michael J. , Smith Lynette M. , Lele Subodh M. , Sasson Aaron R. , Guha Sushovan , Mallya Kavita , Anderson Judy M. , Hollingsworth Michael A. , Batra Surinder K.
Published: November 2013

Purpose: MUC4 shows aberrant expression in early pancreatic lesions and a high specificity for pancreatic cancer. It thus has a high potential to be a sensitive and specific biomarker. Unfortunately, its low serum level limits its diagnostic/prognostic potential. We here report that a multifaceted acute phase protein lipocalin 2, regulated by MUC4, could be a potential diagnostic/prognostic marker for pancreatic cancer.

Experimental Designs and Results: Overexpression/knockdown, luciferase reporter and molecular inhibition studies revealed that MUC4 regulates lipocalin 2 by stabilizing HER2 and stimulating AKT, which results in the activation of NF-κB. Immunohistochemical analyses of lipocalin 2 and MUC4 showed a significant positive correlation between MUC4 and lipocalin 2 in primary, metastatic tissues (Spearman correlation coefficient 0.71, P = 0.002) from rapid autopsy tissue sample from patients with pancreatic cancer as well as in serum and tissue samples from spontaneous KRASG12D mouse pancreatic cancer model (Spearman correlation coefficient 0.98, P < 0.05). Lipocalin 2 levels increased progressively with disease advancement (344.2 ± 22.8 ng/mL for 10 weeks to 3067.2 ± 572.6 for 50 weeks; P < 0.0001). In human pancreatic cancer cases, significantly elevated levels of lipocalin 2 were observed in patients with pancreatic cancer (148 ± 13.18 ng/mL) in comparison with controls (73.27 ± 4.9 ng/mL, P = 0.014). Analyses of pre- and postchemotherapy patients showed higher lipocalin 2 levels in prechemotherapy patients [121.7 ng/mL; 95% confidence interval (CI), 98.1–150.9] in comparison with the postchemotherapy (92.6 ng/mL; 95% CI, 76.7–111.6; P = 0.06) group.

Conclusions: This study delineates the association and the downstream mechanisms of MUC4-regulated elevation of lipocalin-2 (via HER2/AKT/NF-κB) and its clinical significance for prognosis of pancreatic cancer. Clin Cancer Res; 20(3); 688–700. ©2013 AACR.
Germline and Somatic Mutations in Homologous Recombination Genes Predict Platinum Response and Survival in Ovarian, Fallopian Tube, and Peritoneal Carcinomas
Authors: Pennington Kathryn P. , Walsh Tom , Harrell Maria I. , Lee Ming K. , Pennil Christopher C. , Rendi Mara H. , Thornton Anne , Norquist Barbara M. , Casadei Silvia , Nord Alexander S. , Agnew Kathy J. , Pritchard Colin C. , Scroggins Sheena , Garcia Rochelle L. , King Mary-Claire , Swisher Elizabeth M.
Published: November 2013

Purpose: Hallmarks of germline BRCA1/2-associated ovarian carcinomas include chemosensitivity and improved survival. The therapeutic impact of somatic BRCA1/2 mutations and mutations in other homologous recombination DNA repair genes is uncertain.

Experimental Design: Using targeted capture and massively parallel genomic sequencing, we assessed 390 ovarian carcinomas for germline and somatic loss-of-function mutations in 30 genes, including BRCA1, BRCA2, and 11 other genes in the homologous recombination pathway.

Results: Thirty-one percent of ovarian carcinomas had a deleterious germline (24%) and/or somatic (9%) mutation in one or more of the 13 homologous recombination genes: BRCA1, BRCA2, ATM, BARD1, BRIP1, CHEK1, CHEK2, FAM175A, MRE11A, NBN, PALB2, RAD51C, and RAD51D. Nonserous ovarian carcinomas had similar rates of homologous recombination mutations to serous carcinomas (28% vs. 31%, P = 0.6), including clear cell, endometrioid, and carcinosarcoma. The presence of germline and somatic homologous recombination mutations was highly predictive of primary platinum sensitivity (P = 0.0002) and improved overall survival (P = 0.0006), with a median overall survival of 66 months in germline homologous recombination mutation carriers, 59 months in cases with a somatic homologous recombination mutation, and 41 months for cases without a homologous recombination mutation.

Conclusions: Germline or somatic mutations in homologous recombination genes are present in almost one third of ovarian carcinomas, including both serous and nonserous histologies. Somatic BRCA1/2 mutations and mutations in other homologous recombination genes have a similar positive impact on overall survival and platinum responsiveness as germline BRCA1/2 mutations. The similar rate of homologous recombination mutations in nonserous carcinomas supports their inclusion in PARP inhibitor clinical trials. Clin Cancer Res; 20(3); 764–75. ©2013 AACR.
Pertuzumab Protects the Achilles' Heel of Trastuzumab—Emtansine
Authors: Gwin William R. , Spector Neil L.
Published: November 2013

Trastuzumab emtansine (T-DM1) represents a significant advancement in the treatment of HER2+ breast cancers. Its clinical efficacy however will be limited by the development of therapeutic resistance. In this report, the HER3 ligand neuregulin is shown to mediate T-DM1 resistance, which was overcome by administration of pertuzumab, a steric inhibitor of HER2 dimerization. Clin Cancer Res; 20(2); 278–80. ©2013 AACR.
Intracardiac Echocardiography for Detection of Thrombus in the Left Atrial Appendage
Authors: Baran Jakub , Stec Sebastian , Pilichowska-Paszkiet Ewa , Zaborska Beata , Sikora-Frąc Małgorzata , Kryński Tomasz , Michałowska Ilona , Łopatka Rafał , Kułakowski Piotr
Published: November 2013

Background—

Transesophageal echocardiography (TEE) is the gold standard for the exclusion of thrombi in the left atrial appendage (LAA) before ablation for atrial fibrillation. Intracardiac echocardiography (ICE) is used to assist atrial fibrillation ablation; however, it can also be used for LAA imaging. The aim of our study was to determine whether ICE could replace TEE and to identify the optimal ICE placement for LAA visualization.

Methods and Results—

Seventy-six consecutive patients (56 men; mean age, 55±9.6 years) scheduled for atrial fibrillation ablation underwent TEE before the procedure and LAA assessment by ICE. An 8F AcuNav probe was introduced into right atrium, pulmonary artery, and coronary sinus. LAA structure was analyzed by the echocardiographer and electrophysiologist who were blinded to the results of TEE. ICE probe was positioned in the right atrium in all patients, in the pulmonary artery in 64 of 74 (86%) patients, and in the coronary sinus in 49 of 74 (66%) patients. The LAA was properly visualized in 56 of 64 (87.5%) patients from the pulmonary artery versus 13 of 49 (26%) patients from the coronary sinus (
P
<0.001). From the right atrium, the whole LAA cavity could not be seen in any patient. In those patients in whom LAA was visualized properly by ICE, a perfect agreement between ICE and TEE was obtained (both techniques detected LAA thrombus in 2 patients and excluded LAA thrombus in the remaining patients).

Conclusions—

ICE can be used safely and effectively for the evaluation of LAA in patients undergoing atrial fibrillation ablation. ICE imaging from pulmonary artery is accurate for LAA visualization.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01371279.
Complications of Catheter Ablation of Atrial Fibrillation
Authors: Gupta Aakriti , Perera Tharani , Ganesan Anand , Sullivan Thomas , Lau Dennis H. , Roberts-Thomson Kurt C. , Brooks Anthony G. , Sanders Prashanthan
Published: November 2013

Background—

Atrial fibrillation ablation is an established therapy; however, limited data are available on associated complications. This systematic review determines the incidence and potential predictors of acute complications.

Methods and Results—

Electronic searches were conducted in MEDLINE and EMBASE for English scientific literature up to the 18th June 2012. A total of 2065 references were retrieved and evaluated for relevance. Reference lists of retrieved studies and review articles were examined to ensure all relevant studies were included. Data were extracted from 192 studies, total of 83 236 patients. The incidence of periprocedural complications for catheter ablation of atrial fibrillation was 2.9% (95% confidence interval, 2.6–3.2). There was a significant decrease in the acute complication rate in 2007 to 2012 compared with 2000 to 2006 (2.6% versus 4.0%;
P
=0.003). The complication rates reported were higher in prospective studies compared with those that retrospectively described complications (3.5% versus 2.7%;
P
=0.03). There were no significant associations among procedure duration, ablation time or ablation strategy, and acute complication rate.

Conclusions—

Catheter ablation of atrial fibrillation has a low incidence of periprocedural complications. The acute complication rate has decreased significantly in recent years. This may reflect improved catheter technology and experience. The use of different strategies across centers worldwide seems to be safe with no established relationship between procedural variables and complication rate.
Adenosine-Induced Pulmonary Vein Ectopy as a Predictor of Recurrent Atrial Fibrillation After Pulmonary Vein Isolation
Authors: Cheung Jim W. , Lin Frank S. , Ip James E. , Bender Seth R. , Siddiqi Faisal K. , Liu Christopher F. , Thomas George , Markowitz Steven M. , Lerman Bruce B.
Published: November 2013

Background—

Adenosine can unmask dormant pulmonary vein (PV) conduction after PV isolation. Adenosine can also induce ectopy in electrically silent PVs after isolation, possibly via activation of autonomic triggers. We sought to identify the implications of adenosine-induced PV ectopy for atrial fibrillation (AF) recurrence after PV isolation.

Methods and Results—

A total of 152 patients (age, 60±11 years; 63% paroxysmal AF) undergoing PV isolation for AF were studied. After each PV was isolated, adenosine was administered and the presence of adenosine-induced PV reconnection and PV ectopy were recorded. Dormant conduction was targeted with additional ablation. Adenosine-induced PV ectopy was seen in 45 (30%) patients, and dormant conduction was seen in 44 (29%) patients. After a median follow-up of 374 days, 48 (32%) patients had recurrent AF after a single ablation procedure. Rates of freedom from AF among patients with adenosine-induced PV ectopy were significantly lower than patients without adenosine-induced PV ectopy (63% versus 76% at 1 year; log rank, 0.014). Rates of freedom from AF among patients with dormant conduction were also lower than patients without dormant conduction (64% versus 76% at 1 year; log rank, 0.062). With multivariate analysis, adenosine-induced PV ectopy was found to be the only independent predictor of AF after PV isolation (hazard ratio, 1.90; 95% confidence interval, 1.06–3.40;
P
=0.032).

Conclusions—

Adenosine-induced PV ectopy is a predictor of recurrent AF after PV isolation and may be a marker of increased susceptibility to autonomic triggers of AF.
How to Screen Obese Children at Risk for Type 2 Diabetes Mellitus?
Authors: van der Aa Marloes P. , Fazeli Farsani Soulmaz , Kromwijk Lisa A. J. , de Boer Anthonius , Knibbe Catherijne A. J. , van der Vorst Marja M. J.
Published: November 2013

Background. Recommended screening to identify children at risk for diabetes and its precursors impaired glucose tolerance (IGT) and insulin resistance (IR) is fasted plasma glucose (FPG). This study evaluates the added value of fasted plasma insulin (FPI). Methods. This study analyzed routinely collected data of an oral glucose tolerance test (OGTT) of 311 obese children (age 10.8 ± 3.2 years). Diabetes and IGT were defined according to the American Diabetes Association criteria, IR as homeostasis model assessment (HOMA)-IR ≥3.4. Results. Cases diagnosed with an OGTT if FPG ≥5.6 mmol/L, compared with an OGTT performed if FPG ≥5.6 mmol/L or HOMA-IR ≥3.4, were, respectively, 4 (80%) versus 5 (100%) with diabetes, 7 (28%) versus 16 (64%) with IGT, and 0 (0%) versus 93 (100%) with IR. Conclusions. Screening with FPG and FPI has equal burden compared with screening with FPG alone, identifies all patients with diabetes, and identifies more patients with precursors of diabetes.
State and Federal Policies for School Facility Construction
Authors: Davis Thomas E.
Published: November 2013

Background: The Ohio School Facilities Commission was set up in response to litigation compelling the state to achieve a more equitable distribution in the quality of school facilities. The American Recovery and Reinvestment Act (ARRA) was a federal policy to stimulate the United States economy and support school facility construction. These two programs provide an opportunity to compare a state-run program to a federal one. Purpose: This study analyzes the distribution of school and community resources across school districts in Michigan and Ohio, two otherwise similar states with very different policies to support school facilities. Using the year prior to the implementation of the ARRA as a baseline, this study then compares the allocation of Qualified School Construction Bonds (QSCB) provided under the ARRA. Research Design: Using Michigan as a control group because of the weak state support for school construction, the analysis shows the distribution and variation of school building capital, community resources, educational inputs, and student outcomes across districts in both states. Based on these indicators, districts that received QSCBs are compared with districts that did not. Findings: Ohio does appear to have a more equitable distribution of capital facilities but the QSCB allocations in Ohio do not appear to be noticeably more equalizing than those in Michigan. Moreover, the allocations in both states went, on average, to districts above the mean on a number of measures of community resources, educational inputs, and student outcomes.
Healthy and active ageing: Social capital in health promotion
Authors: Koutsogeorgou Eleni , Davies John Kenneth , Aranda Kay , Zissi Anastasia , Chatzikou Maria , Cerniauskaite Milda , Quintas Rui , Raggi Alberto , Leonardi Matilde
Published: November 2013

Objectives:

This paper examines the context of health promotion actions that are focused on/contributing to strengthening social capital by increasing community participation, reciprocal trust and support as the means to achieve better health and more active ageing.

Method:

The methodology employed was a literature review/research synthesis, and a thematic analysis.

Results:

Four core themes emerged from the analysis: a) active ageing; b) the relationship between social capital and ageing; c) the importance of social capital in health promotion; and d) policy implications. The role of social capital in health promotion stresses empowerment, intergenerational support, the building of social trust, and the need to tackle loneliness among older adults. The importance of community/social participation emerged from the literature review as a key contributor to the maintenance and promotion of a healthier ageing population.

Conclusion:

Supporting long-term social capital building within communities can lead to improved public health and well-being for an ageing population.
Analysis of Cross-Cultural Comparability of PISA 2009 Scores
Authors: Kankaraš Miloš , Moors Guy
Published: November 2013

The Program for International Student Assessment (PISA) is a large-scale cross-national study that measures academic competencies of 15-year-old students in mathematics, reading, and science from more than 50 countries/economies around the world. PISA results are usually aggregated and presented in so-called “league tables,” in which countries are compared and ranked in each of the three scales. However, to compare results obtained from different groups/countries, one must first be sure that the tests measure the same competencies in all cultures. In this paper, this is tested by examining the level of measurement equivalence in the 2009 PISA data set using an item response theory approach (IRT) and analyzing differential item functioning (DIF). Measurement in-equivalence was found in the form of uniform DIF. In-equivalence occurred in a majority of test questions in all three scales researched and is, on average, of moderate size. It varies considerably both across items and across countries. When this uniform DIF is accounted for in the in-equivalent model, the resulting country scores change considerably in the cases of the “Mathematics,” “Science,” and especially, “Reading” scale. These changes tend to occur simultaneously and in the same direction in groups of regional countries. The most affected seems to be Southeast Asian countries/territories whose scores, although among the highest in the initial, homogeneous model, additionally increase when accounting for in-equivalence in the scales.
‘We don’t have no neighbourhood’: Advanced marginality and urban agriculture in Detroit
Authors: Draus Paul Joseph , Roddy Juliette , McDuffie Anthony
Published: November 2013

This paper is based on qualitative interviews ( n=20) conducted with individuals working or residing within a heavily depopulated section of the city of Detroit. This area is the projected site of an urban agriculture (UA) project, which proposes to utilise vacant land and economically marginalised residents to produce marketable products and services. With a few exceptions, neighbourhood respondents had little hope of improvement occurring in the neighbourhood anytime soon, and few expectations for UA to alter the daily life or social dynamic of the area. These findings are framed and interpreted using Wacquant’s (1999) concept of advanced marginality and Sampson’s (2012) arguments concerning neighbourhood effects. While some neighbourhood improvement efforts were viewed positively, others were regarded with intense suspicion, indicating that idealistic UA efforts may have some work to do in terms of engaging residents and offsetting legacies of displacement as well as on-going marginalisation.
Institutionally configured risk: Assessing urban resilience and disaster risk reduction to heat wave risk in London
Authors: Zaidi R Zehra , Pelling Mark
Published: November 2013

This paper argues for an increased emphasis on the institutions of risk governance and management in understanding urban resilience. This moves analysis of vulnerability away from a focus on individuals to also consider risk management regimes as co-productive of vulnerability and resilience in the City. This is illustrated through the application of an Adaptive Capacity Index to unpack the role played by formal governance institutions in mediating resilience to extreme heat events in the empirical case of London. Analysis shows that the configuration of risk at the institutional level directs heat wave risk management through the health services, and operationalises it during the emergency phase of hazard onset. This misses an important opportunity for integrating individual and regime level risk management initiatives, which we proposed can be worked out through greater collaboration with social services and interaction with those caring for the vulnerable, has yet to be fully integrated into planning and practice in London and elsewhere.
Visualizing Sequences in the Social Sciences
Authors: Fasang Anette Eva , Liao Tim Futing
Published: November 2013

Visualization is a potentially powerful tool for exploration and complexity reduction of categorical sequence data. This article discusses currently available sequence visualization against established criteria for graphical excellence in the visual display of quantitative information. Existing sequence graphs fall into two groups: They either represent categorical sequences or summarize them. The authors propose relative frequency sequence plots as an informative way of graphing sequence data and as a bridge between data representation graphs and data summarization graphs. The efficacy of the proposed plot is assessed by the R2 and the F statistics. The applicability of the proposed graphs is demonstrated using data from the German Life History Study on women’s family formation.
Immunogenicity/Hypersensitivity of Biologics
Authors: Leach Michael W. , Rottman James B. , Hock M. Benjamin , Finco Deborah , Rojko Jennifer L. , Beyer Joseph C.
Published: November 2013

This continuing education course was designed to provide an overview of the immunologic mechanisms involved in immunogenicity and hypersensitivity reactions following administration of biologics in nonclinical toxicity studies, the methods used to determine whether such reactions are occurring, and the associated clinical and anatomic pathology findings. Hypersensitivity reactions have classically been divided into type I, II, III, and IV reactions; type I and III reactions are those most often observed following administration of biologics. A variety of methods can be used to detect these reactions. Antemortem methods include hematology; detection of antidrug antibodies, circulating immune complexes and complement fragments, and immunoglobulin E in serum; tests for serum complement activity; and evaluation of complement receptor 1 on erythrocytes. Postmortem methods include routine light microscopy and electron microscopy, which can demonstrate typical findings associated with hypersensitivity reactions, and immunohistochemistry, which can detect the presence of immune complexes in tissues, including the detection of the test article. A final determination of whether findings are related to a hypersensitivity reaction in individual animals or across the entire study should rely on the overall weight of evidence, as findings indicative of these reactions are not necessarily consistent across all affected animals.
A Longitudinal Approach to Understanding the Relationship Between Symptom Status and QOL
Authors: Sousa Karen H. , Kwok Oi-Man , Schmiege Sarah J. , West Stephen G.
Published: November 2013

This study demonstrates how a variant of growth curve modeling known as longitudinal parallel-process modeling can yield an understanding of the effect of symptoms on quality of life (QOL). A two-level hierarchical linear model with random intercepts and slopes was implemented within a structural equation modeling approach. The data ( N = 367) comes from a large database of persons with HIV-associated illness. Twenty-three symptoms based on the Sign and Symptom Checklist for Persons with HIV disease and items measuring QOL from the general health status scales were used. Each respondent completed from 1 to 11 questionnaires. The number of reported symptoms had a significant association with patient QOL over time. These findings suggest that appropriate symptom management has the potential to improve patient QOL. This study demonstrates how a state-of-the-art longitudinal modeling technique evaluates the relationship between concurrent rates of change in measurements of two relevant variables.
Video-assisted mediastinoscopic resection of mediastinal cyst (lymphangioma)
Authors: Sadrizadeh Ali , Bagheri Reza , Afghani Reza , Molaei Mehdi
Published: November 2013

Mediastinal cysts account for 20% of all mediastinal masses. Symptomatic cysts need treatment, and surgical excision is the treatment of choice. One approach to resect them is video-assisted mediastinoscopy. An 80-year-old man with cough and dyspnea at rest was referred for evaluation. Chest computed tomography revealed a mediastinal cyst. Because of his symptoms, he was a candidate for surgery, and the cyst was resected by video-assisted mediastinoscopy through a cervical incision. Video-assisted mediastinoscopy is a safe and effective approach for complete resection of mediastinal cysts.
The effects of a physical exercise programme after radical cystectomy for urinary bladder cancer. A pilot randomized controlled trial
Authors: Porserud Andrea , Sherif Amir , Tollbäck Anna
Published: November 2013

Objective:

Assessment of feasibility and effects of an exercise training programme in patients following cystectomy due to urinary bladder cancer.

Design:

Single-blind, pilot, randomized controlled trial.

Setting:

University hospital, Sweden.

Subjects:

Eighteen patients (64–78 years), of 89 suitable, cystectomized due to urinary bladder cancer, were randomized after hospital discharge to intervention or control.

Interventions:

The 12-week exercise programme included group exercise training twice a week and daily walks. The control group received only standardized information at discharge.

Main outcome measures:

Trial eligibility and compliance to inclusion were registered. Assessments of functional capacity, balance, lower body strength and health-related quality of life (HRQoL) with SF-36.

Results:

Out of 122 patients 89 were eligible, but 64 did not want to participate/were not invited. Twenty-five patients were included, but 7 dropped out before randomization. Eighteen patients were randomized to intervention or control. Thirteen patients completed the training period. The intervention group increased walking distance more than the control group, 109 m (75–177) compared to 62 m (36–119) ( P = 0.013), and role physical domain in SF-36 more than the control group ( P = 0.031). Ten patients were evaluated one year postoperatively. The intervention group had continued increasing walking distance, 20 m (19–36), whereas the control group had shortened the distance −15.5 m (−43 to −5) ( P = 0.010).

Conclusions:

A 12-week group exercise training programme was not feasible for most cystectomy patients. However, functional capacity and the role-physical domain in HRQoL increased in the short and long term for patients in the intervention group compared with controls.
A multicentre postal survey investigating the contribution of illness perceptions, coping and optimism to quality of life and mood in adults with muscle disease
Authors: Graham Christopher D , Weinman John , Sadjadi Reza , Chalder Trudie , Petty Richard , Hanna Mike G , Turner Chris , Parton Matt , Maddison Paul , Radunovic Aleksandar , Longman Cheryl , Robb Yvonne , Bushby Kate , Hilton-Jones David , Rose Michael R
Published: November 2013

Objective:

To replicate the finding that illness perceptions influence quality of life in adults with muscle disease and to explore the additional influence of coping and optimism on quality of life and mood.

Design:

A postal survey including questionnaires recording quality of life, mood, illness perceptions, optimism, coping and functional impairment.

Setting:

National Health Service muscle clinics in the United Kingdom.

Participants:

A convenience sample of adults with muscle disease.

Interventions:

Not applicable.

Main outcome measures:

Individualised Neuromuscular Quality of Life Questionnaire, Hospital Anxiety and Depression Scale.

Results:

A total of 226 completed questionnaires were returned. Although functional impairment explained most of the variance in three out of eight quality of life domains, psychological factors explained greater amounts of variance (between 19% and 52% of variance) in all other quality of life domains and in both mood domains (between 45% and 48% of variance). Overall, illness perceptions explained much of the variance in quality of life and mood score (between 5% and 37% of variance), while coping (up to 8% of variance) and optimism (up to 15% of variance) explained smaller amounts of variance.

Conclusion:

The results confirm that illness perceptions are associated with quality of life in muscle disease and suggest that they also influence mood. The addition of optimism and coping variables into the analysis yielded small increases in the proportions of variance in quality of life and mood which were explained. These results have implications for the composition of future psychological interventions.
Efficacy of microcurrent therapy in infants with congenital muscular torticollis involving the entire sternocleidomastoid muscle: a randomized placebo-controlled trial
Authors: Kwon Dong Rak , Park Gi Young
Published: November 2013

Objective:

To compare the effects of a combination of therapeutic exercise and ultrasound with or without additional microcurrent therapy in infants with congenital muscular torticollis involving the entire sternocleidomastoid muscle.

Design:

Prospective, randomized, placebo-controlled trial.

Setting:

An outpatient rehabilitation clinic in a tertiary university hospital.

Subjects:

Infants ( n = 20) with congenital muscular torticollis involving the entire sternocleidomastoid muscle.

Interventions:

Group 1 comprised 10 infants who received therapeutic exercise with ultrasound alone and Group 2 comprised 10 infants who received the same treatment with microcurrent therapy.

Main measures:

Passive cervical rotational range of motion was measured at before treatment and one, two, three, and six months after initial treatment. Thickness, cross-sectional area, and red pixel intensity on colour histograms, which were all assessed before treatment and at three months after initial treatment. Additionally, the duration of treatment was measured.

Results:

The mean passive cervical rotational range of motion measured at three months posttreatment was significantly greater in Group 2 (101.1°) than that in Group 1 (86.4°), and the thickness, cross-sectional area, and red pixel intensity of the affected sternocleidomastoid muscle were all less in Group 2 (7.8 mm, 100.3 mm2, and 126.1, respectively) than those in Group 1 (9.6 mm, 121.5 mm2, and 140.5, respectively). The mean duration of treatment was significantly shorter in Group 2 (2.6 months) than in Group 1 (6.3 months).

Conclusions:

Microcurrent therapy may increase the efficacy of therapeutic exercise with ultrasound for the treatment of congenital muscular torticollis involving the entire sternocleidomastoid muscle.
FIRM: Sampling-based feedback motion-planning under motion uncertainty and imperfect measurements
Authors: Agha-mohammadi Ali-akbar , Chakravorty Suman , Amato Nancy M
Published: November 2013

In this paper we present feedback-based information roadmap (FIRM), a multi-query approach for planning under uncertainty which is a belief-space variant of probabilistic roadmap methods. The crucial feature of FIRM is that the costs associated with the edges are independent of each other, and in this sense it is the first method that generates a graph in belief space that preserves the optimal substructure property. From a practical point of view, FIRM is a robust and reliable planning framework. It is robust since the solution is a feedback and there is no need for expensive replanning. It is reliable because accurate collision probabilities can be computed along the edges. In addition, FIRM is a scalable framework, where the complexity of planning with FIRM is a constant multiplier of the complexity of planning with PRM. In this paper, FIRM is introduced as an abstract framework. As a concrete instantiation of FIRM, we adopt stationary linear quadratic Gaussian (SLQG) controllers as belief stabilizers and introduce the so-called SLQG-FIRM. In SLQG-FIRM we focus on kinematic systems and then extend to dynamical systems by sampling in the equilibrium space. We investigate the performance of SLQG-FIRM in different scenarios.
Understanding ‘anticipatory governance’
Authors: Guston David H
Published: November 2013

Anticipatory governance is ‘a broad-based capacity extended through society that can act on a variety of inputs to manage emerging knowledge-based technologies while such management is still possible’. It motivates activities designed to build capacities in foresight, engagement, and integration – as well as through their production ensemble. These capacities encourage and support the reflection of scientists, engineers, policy makers, and other publics on their roles in new technologies. This article reviews the early history of the National Nanotechnology Initiative in the United States, and it further explicates anticipatory governance through exploring the genealogy of the term and addressing a set of critiques found in the literature. These critiques involve skepticism of three proximities of anticipatory governance: to its object, nanotechnology, which is a relatively indistinct one; to the public, which remains almost utterly naïve toward nanotechnology; and to technoscience itself, which allegedly renders anticipatory governance complicit in its hubris. The article concludes that the changing venues and the amplification within them of the still, small voices of folks previously excluded from offering constructive visions of futures afforded by anticipatory governance may not be complete solutions to our woes in governing technology, but they certainly can contribute to bending the long arc of technoscience more toward humane ends.
Red Tape, Resigned Satisfaction, Public Service Motivation, and Negative Employee Attitudes and Behaviors
Authors: Quratulain Samina , Khan Abdul Karim
Published: November 2013

We examine the effect of red tape on resigned satisfaction, Public Service Motivation (PSM), and negative employee attitudes and behaviors. Based on responses of 217 public servants, this study demonstrates the role of resigned satisfaction as a mediating mechanism for transferring the effect of red tape on negative employee outcomes. PSM was hypothesized as an individual difference variable that can either mitigate or exacerbate the indirect effect of red tape on employee attitudes and behaviors. Our study is among the first few that demonstrate the dark side of PSM. We found that PSM exacerbates the adverse effects of red tape on negative employee attitudes and behaviors and that these effects are transmitted through the mechanism of resigned satisfaction. These findings are at odds with the dominant conception that employees having higher levels of PSM tend to pursue their motivations of public service despite excessive formalization and procedural constraints.
Protection mechanism of a flame-retarded polyamide 6 nanocomposite
Authors: Samyn Fabienne , Bourbigot Serge
Published: November 2013

Investigations have been performed to determine the causes of the synergistic effect observed when a combination of flame retardants (FR; aluminum phosphinate/melamine polyphosphate) and organomodified montmorillonite (o-MMT) is used in polyamide 6 (PA6). Structures obtained at different stage of degradation in cone calorimeter experiments for the PA6, PA6/FR, PA6/o-MMT, PA6/FR/o-MMT are compared. The evolution of the chemical species formed according to the stages of degradation together with the characterization of the resistance of the char have enabled to elucidate the mechanism of protection involved for PA6/FR/o-MMT. Infrared characterizations have demonstrated that the species formed are degradation products of the components of the formulation that are also observed for PA6/FR and PA6/o-MMT and do not explain the improved performances. However, the structure of the char with clay distinguishes itself with a very specific small closed-cells foamed structure exhibiting an enhanced char strength. A detailed comparison of the mode of protection involved when using FR and a combination of FR/o-MMT when submitted to fire is proposed.
Polls, coalitions and strategic voting under proportional representation
Authors: Herrmann Michael
Published: November 2013

How do polls influence strategic voting under proportional representation? This paper derives a strategic calculus of voting for coalitions that generates testable predictions about the effects of polls on strategic voting in elections involving four or more parties. Incentives of leftist voters to vote for a centrist over a noncentrist party are shown to increase with the difference in expected seats between the prospective right-wing and left-wing coalitions (and vice versa for rightist voters). Centrist voters’ incentives to vote for a center-left vs a center-right party are also shown to depend on the relative strengths of the right-wing and left-wing coalitions. Importantly, the strategic voting incentives studied here do not depend on the presence of electoral thresholds or other features of the electoral system. The predictions are tested with survey data from parliamentary elections in Austria and Germany.
Supermajority voting, social indifference and status quo constraints
Authors: Kline Reuben
Published: November 2013

We develop several results related to equilibrium in sophisticated voting under an amendment agenda procedure and supermajoritarian voting rules. Contrary to the simple majority case, we demonstrate that attainable equilibria are a function of the location of the status quo ex ante as well as the tie-breaking rule in place. Most importantly, we demonstrate that the Banks set (the set of sophisticated voting outcomes) does not reduce to the core under certain conditions. Moreover, in generalizing and extending the results in Colomer (1999), we define three analytically distinct regions, defined by the location of the status quo alternative, which determine the extent of the intersection between the Banks set and the core.
Awe, Uncertainty, and Agency Detection
Authors: Valdesolo Piercarlo , Graham Jesse
Published: November 2013

Across five studies, we found that awe increases both supernatural belief (Studies 1, 2, and 5) and intentional-pattern perception (Studies 3 and 4)—two phenomena that have been linked to agency detection, or the tendency to interpret events as the consequence of intentional and purpose-driven agents. Effects were both directly and conceptually replicated, and mediational analyses revealed that these effects were driven by the influence of awe on tolerance for uncertainty. Experiences of awe decreased tolerance for uncertainty, which, in turn, increased the tendency to believe in nonhuman agents and to perceive human agency in random events.
Mortality in neuropsychiatric systemic lupus erythematosus (NPSLE)
Authors: Zirkzee EJM , Huizinga TWJ , Bollen ELEM , Buchem MA van , Middelkoop HAM , Wee NJA van der , Cessie S le , Steup-Beekman GM
Published: November 2013

The standardized mortality ratio (SMR) for systemic lupus erythematosus (SLE) is three; SMR increases to six in case of renal involvement. Up to now data on survival in case of neuropsychiatric involvement in SLE (NPSLE) have been scarce, therefore we calculated an SMR for NPSLE. Furthermore, we identified characteristics that influenced survival by Cox regression analyses. All patients suspected of NPSLE in our center since 1989 were evaluated and included in this study when a diagnosis of primary NPSLE could be established. Patient’s life/death status was tracked using the civic registries. Thirty-two (19%) of the 169 included NPSLE patients died within a median follow-up period of six years (range 0.5–24 years). This resulted in a significantly increased mortality rate compared to the general population: SMR 9.5 (95% CI 6.7–13.5). Hazard ratios (HRs) were highest in patients with acute confusional state (HR 3.4) and older age at diagnosis of NPSLE (HR 1.1). A decreased mortality risk was seen with the prescription of antiplatelet therapy (HR 0.22). The time period in which NPSLE was diagnosed did not significantly influence survival. Most frequent causes of death were infection and NPSLE itself.
Nonconvulsive Status Epilepticus in a Palliative Care Unit
Authors: Samala Renato V. , Parala-Metz Armida , Davis Mellar P.
Published: November 2013

The search for an underlying cause of altered mental status not uncommonly becomes more challenging in the hospice and palliative care setting. Due to multiple coexisting conditions that affect mental status and shifting goals of care, discerning that single cause in this venue can become frustrating and even nonbeneficial at times. We present a case of nonconvulsive status epilepticus (NCSE), which multiple reports have shown to be a rarely contemplated cause of impaired consciousness. A concise review of NCSE follows, with emphasis on conditions that present similarly, precipitating factors, diagnostic and therapeutic considerations, and prognostic implications. Nonconvulsive status epilepticus is a reversible cause of altered consciousness, particularly when recognized promptly. In a palliative care unit, treatment should ultimately be guided by the patient’s goals of care.