bluuebunny/crossref_metadata_2025 huggingface dataset:
Designing a multi-slate reading environment to support active reading activities
Authors: Chen Nicholas , Guimbretiere Francois , Sellen Abigail
Published: November 2012

Despite predictions of the paperless office, most knowledge workers and students still rely heavily on paper in most of their document practices. Research has shown that paper's dominance can be attributed to the fact that it supports a broad range of these users' diverse reading requirements. Our analysis of the literature suggests that a new class of reading device consisting of an interconnected environment of thin and lightweight electronic slates could potentially unify the distinct advantages of e-books, PCs, and tabletop computers to offer an electronic reading solution providing functionality comparable to, or even exceeding, that of paper. This article presents the design and construction of such a system. In it, we explain how data can be mapped to slates, detail interactions for linking the slates, and describe tools that leverage the connectivity between slates. A preliminary study of the system indicates that such a system has the potential of being an electronic alternative to paper.
Crafting technology
Authors: Buechley Leah , Perner-Wilson Hannah
Published: November 2012

This article examines the practice of electronics building in the context of other crafts. We compare the experience of making electronics with the experiences of carving, sewing, and painting. Our investigation is grounded in a survey of 40 practicing craftspeople who are working in each of these disciplines. We then use this survey as a foundation for a discussion of hybrid craft—integrations of electronics with carving, sewing, and painting. We present examples of hybrid craft and discuss the ways in which blended practices can enrich and diversify technology.
The impact of interface affordances on human ideation, problem solving, and inferential reasoning
Authors: Oviatt Sharon , Cohen Adrienne , Miller Andrea , Hodge Kumi , Mann Ariana
Published: November 2012

This article presents two studies investigating how computer interface affordances influence basic cognition, including ideational fluency, problem solving, and inferential reasoning. In one study comparing interfaces with different input capabilities, students expressed 56% more nonlinguistic representations (diagrams, symbols, numbers) when using pen interfaces. A linear regression confirmed that nonlinguistic communication directly mediated a substantial increase (38.5%) in students' ability to produce appropriate science ideas. In contrast, students expressed 41% more linguistic content when using a keyboard-based interface, which mediated a drop in science ideation. A follow-up study pursued the question of how interfaces that prime nonlinguistic communication so effectively facilitate cognition. This study examined the relation between students' expression of nonlinguistic representations and their inference accuracy when using analogous digital and non-digital pen tools. Perhaps surprisingly, the digital pen interface stimulated construction of more diagrams, more correct Venn diagrams, and more accurate domain inferences. Students' construction of multiple diagrams to represent a problem also directly suppressed overgeneralization errors, which were the most common inference failure. These research results reveal that computer interfaces have communications affordances which elicit communication patterns that can substantially stimulate or impede basic cognition. Implications are discussed for designing new digital tools for thinking, with an emphasis on nonlinguistic and especially spatial representations that are most poorly supported by current keyboard-based interfaces.
Co-narrating a conflict
Authors: Zancanaro Massimo , Stock Oliviero , Eisikovits Zvi , Koren Chaya , Weiss Patrice L.
Published: November 2012

A multi-user tabletop interface was designed to support reconciliation of a conflict aimed at shifting hostile attitudes and achieving a greater understanding of another viewpoint. The interface provided a setting for face-to-face shared narration and support for the management of disagreements. The interface allows for escalation and de-escalation of the conflict emerging in the shared narration and requires that participants perform joint actions when a contribution to the story is to be removed from the overall narration. A between-subjects experiment compared the tabletop interface and a desktop multimedia interface with mixed pairs (male Israeli-Jewish and Palestinian-Arab youth). The results demonstrated that the experience with the tabletop interface appears to be motivating and, most importantly, produces at least a short-term shift of attitude toward the other.
Creating a General (Family) Practice Epidemiological Database in Ireland - Data Quality Issue Management
Authors: Collins Claire , Janssens Kelly
Published: November 2012

In Ireland, while detailed information is available regarding hospital attendance, little is known regarding general (family) practice attendance. However, it is conservatively estimated that there are almost nine times as many general practice encounters than there are hospital encounters each year in Ireland. This represents a very significant gap in health information. Indeed, general practice has been shown in other countries to be an important and rich source of information about the health of the population, their behaviors and their utilization of health services. Funded by the Health Information and Quality Authority (HIQA), the Irish College of General Practitioners (ICGP) undertook a feasibility study of diagnostic coding of routinely entered patient data and the creation of a national general practice morbidity and epidemiological database (GPMED project). This article outlines the process of data quality issue management undertaken.

The study’s findings suggest that the quality of data collection and reporting structures available in general practice throughout Ireland at the outset of this project were not adequate to permit the creation of a database of sufficient quality for service planning and policy or epidemiological research. Challenges include the dearth of a minimum standard of data recorded in consultations by GPs and the absence of the digital data recording and exporting infrastructure within Irish patient management software systems. In addition, there is at present a lack of recognition regarding the value of such data for patient management and service planning---including importantly, data collectors who do not fully accept the merit of maintaining data, which has a direct consequence for data quality. The work of this project has substantial implications for the data available to the health sector in Ireland and contributes to the knowledge base internationally regarding general practice morbidity data.
Improving the Data Quality of Drug Databases using Conditional Dependencies and Ontologies
Authors: Curé Olivier
Published: November 2012

Many health care systems and services exploit drug related information stored in databases. The poor data quality of these databases, e.g. inaccuracy of drug contraindications, can lead to catastrophic consequences for the health condition of patients. Hence it is important to ensure their quality in terms of data completeness and soundness.

In the database domain, standard Functional Dependencies (FDs) and INclusion Dependencies (INDs), have been proposed to prevent the insertion of incorrect data. But they are generally not expressive enough to represent a domain-specific set of constraints. To this end, conditional dependencies, i.e. standard dependencies extended with tableau patterns containing constant values, have been introduced and several methods have been proposed for their discovery and representation. The quality of drug databases can be considerably improved by their usage.

Moreover, pharmacology information is inherently hierarchical and many standards propose graph structures to represent them, e.g. the Anatomical Therapeutic Chemical classification (ATC) or OpenGalen’s terminology. In this article, we emphasize that the technologies of the Semantic Web are adapted to represent these hierarchical structures, i.e. in RDFS and OWL. We also present a solution for representing conditional dependencies using a query language defined for these graph oriented structures, namely SPARQL. The benefits of this approach are interoperability with applications and ontologies of the Semantic Web as well as a reasoning-based query execution solution to clean underlying databases.
Data Management within mHealth Environments
Authors: O’Donoghue John , Herbert John
Published: November 2012

Pervasive environments generate large quantities of data, originating from backend servers, portable devices, and wireless mobile sensors. Pervasive sensing devices that monitor properties of the environment (including human beings) can be a large data source. Unprocessed datasets may include data that is faulty and irrelevant, and data that is important and useful. If not managed correctly the large amount of data from a data-rich pervasive environment may result in information overload or delivery of incorrect information.

Context-sensitive quality data management aims to gather, verify, process, and manage the multiple data sources in a pervasive environment in order to deliver high quality, relevant information to the end-user. Managing the quality of data from different sources, correlating related data, and making use of context, are all essential in providing end users with accurate and meaningful data in real time. This requirement is especially true for critical applications such as in a medical environment.

This article presents the Data Management System (DMS) architecture. It is designed to deliver quality data service to its users. The DMS architecture employs an agent-based middleware to intelligently and effectively manage all pervasive data sources, and to make use of context to deliver relevant information to the end-user. Two of the DMS components are presented: (1) data validation and (2) data consistency. The DMS components have been rigorously evaluated using various medical-based test cases.

This article demonstrates a careful, precise approach to data based on the quality of the data and the context of its use. It emphasises the DMS architecture and the role of software agents in providing quality data management.
Transcriptome of the NTS in exercise-trained spontaneously hypertensive rats: implications for NTS function and plasticity in regulating blood pressure
Authors: Waki Hidefumi , Gouraud Sabine S. , Bhuiyan Mohammad E. R. , Takagishi Miwa , Yamazaki Toshiya , Kohsaka Akira , Maeda Masanobu
Published: November 2012

The nucleus tractus solitarii (NTS) controls the cardiovascular system during exercise, and alteration of its function may underlie exercise-induced cardiovascular adaptation. To understand the molecular basis of the NTS's plasticity in regulating blood pressure (BP) and its potential contribution to the antihypertensive effects, we characterized the gene expression profiles at the level of the NTS after long-term daily wheel running in spontaneously hypertensive rats (SHRs). Genome-wide microarray analysis was performed to screen for differentially expressed genes in the NTS between exercise-trained (12 wk) and control SHRs. Pathway analysis using the Kyoto Encyclopedia of Genes and Genomes database revealed that daily exercise altered the expression levels of NTS genes that are functionally associated with metabolic pathways (5 genes), neuroactive ligand-receptor interactions (4 genes), cell adhesion molecules (3 genes), and cytokine-cytokine receptor interactions (3 genes). One of the genes that belonged to the neuroactive ligand-receptor interactions category was histamine receptor H1. Since we confirmed that the pressor response induced by activation of this receptor is increased after long-term daily exercise, it is suggested that functional plasticity in the histaminergic system may mediate the facilitation of blood pressure control in response to exercise but may not be involved in the lowered basal BP level found in exercise-trained SHRs. Since abnormal inflammatory states in the NTS are known to be prohypertensive in SHRs, altered gene expression of the inflammatory molecules identified in this study may be related to the antihypertensive effects in exercise-trained SHRs, although such speculation awaits functional validation.
Current analysis platforms and methods for detecting copy number variation
Authors: Li Wenli , Olivier Michael
Published: November 2012

Copy number variation (CNV), generated through duplication or deletion events that affect one or more loci, is widespread in the human genomes and is often associated with functional consequences that may include changes in gene expression levels or fusion of genes. Genome-wide association studies indicate that some disease phenotypes and physiological pathways might be impacted by CNV in a small number of characterized genomic regions. However, the pervasiveness and full impact of such variation remains unclear. Suitable analytic methods are needed to thoroughly mine human genomes for genomic structural variation, and to explore the interplay between observed CNV and disease phenotypes, but many medical researchers are unfamiliar with the features and nuances of recently developed technologies for detecting CNV. In this article, we evaluate a suite of commonly used and recently developed approaches to uncovering genome-wide CNVs and discuss the relative merits of each.
Hyperspectral Anomaly Detection: Comparative Evaluation in Scenes with Diverse Complexity
Authors: Borghys Dirk , Kåsen Ingebjørg , Achard Véronique , Perneel Christiaan
Published: November 2012

Anomaly detection (AD) in hyperspectral data has received a lot of attention for various applications. The
aim of anomaly detection is to detect pixels in the hyperspectral data cube whose spectra differ significantly from
the background spectra. Many anomaly detectors have been proposed in the literature. They differ in the way the
background is characterized and in the method used for determining the difference between the current pixel and
the background. The most well‐known anomaly detector is the RX detector that calculates the Mahalanobis distance
between the pixel under test (PUT) and the background. Global RX characterizes the background of the complete
scene by a single multivariate normal probability density function. In many cases, this model is not appropriate
for describing the background. For that reason a variety of other anomaly detection methods have been developed.
This paper examines three classes of anomaly detectors: subspace methods, local methods, and segmentation‐based
methods. Representative examples of each class are chosen and applied on a set of hyperspectral data with diverse
complexity. The results are evaluated and compared.
Feasibility and Acceptability of Screening and Brief Interventions to Address Alcohol and Other Drug Use among Patients Presenting for Emergency Services in Cape Town, South Africa
Authors: Myers Bronwyn , Stein Dan J. , Mtukushe Bulelwa , Sorsdahl Katherine
Published: November 2012

Despite evidence from high income countries, it is not known whether screening and brief interventions (SBI) for alcohol and other drug (AOD) use are feasible to implement in low and middle income countries. This paper describes the feasibility and acceptability of a peer-led SBI for AOD-using patients presenting with injuries at emergency services in Cape Town, South Africa. Data were extracted from program records on the number of eligible patients screened and the number of program refusals. A questionnaire examined preliminary responses to the intervention for 30 patients who had completed the program and 10 emergency personnel. Peer counselors were also interviewed to identify barriers to implementation. Of the 1458 patients screened, 21% (305) met inclusion criteria, of which 74% (225) were enrolled in the intervention. Of the 30 patients interviewed, most (83%) found the program useful. Emergency personnel were supportive of the program but felt that visibility and reach could improve. Peer counselors identified the need for better integration of the program into emergency services and for additional training and support. In conclusion, with limited additional resources, peer-led SBIs for AOD use are feasible to conduct in South African emergency services and are acceptable to patients and emergency personnel.
Refractory Uveitis in Patient with Castleman Disease Successfully Treated with Tocilizumab
Authors: Oshitari Toshiyuki , Kajita Fusae , Tobe Aya , Itami Makiko , Yotsukura Jiro , Baba Takayuki , Yamamoto Shuichi
Published: November 2012

Although multicentric Castleman disease is a rare but life-threatening disease, eye complications are extremely uncommon. We present a case of refractory uveitis accompanied with Castleman disease successfully treated with tocilizumab. A 58-year-old man with Castleman disease was introduced for refractory uveitis to Chiba University Hospital. Large cells were detected in the anterior chamber and increased vascular permeability of retinal vessels has been found in both eyes. Although the patient was treated with oral and eye drop steroid treatment, the uveitis symptoms had not decreased. The serum levels of CRP and IL-6 were increased. The level of IL-6 concentration in the anterior chamber was the same as the serum level of IL-6. The humanized anti-IL-6 receptor-antibody (tocilizumab) was administrated for the patient because of poor general condition. After tocilizumab treatment, large cells in the anterior chamber were undetectable and vascular permeability was improved in FA. The serum levels of CRP and IL-6 decreased and the general condition improved. The side effect of tocilizumab was not observed during the treatment. Tocilizumab treatment was significantly effective for uveitis accompanied with Castleman disease. Although it is extremely rare, uveitis accompanied with Castleman disease may be one of the hallmarks to consider tocilizumab treatment.
SOX2 Autoantibodies As Noninvasive Serum Biomarker for Breast Carcinoma
Authors: Sun Yu , Zhang Rui , Wang Minjie , Zhang Yuan , Qi Jun , Li Jinming
Published: November 2012

Background: A clear association has been established between antibodies to the transcription factor sex-determining region Y (SRY)-box 2 (SOX2) and small cell lung cancer. In light of the pathologic role of SOX2 and its aberrant expression in breast cancer, we measured serum SOX2 autoantibodies (SOX2-Abs) in breast cancer patients.

Methods: The presence of SOX2-Abs was determined by an indirect enzyme-linked immunosorbent assay (ELISA) in sera from 282 patients with breast cancer, 78 patients with benign breast disease, and 194 healthy women.

Results: SOX2-Abs were more prevalent in patients with breast cancer (18.4%) compared with healthy women (2.6%, P < 0.0001), and patients with benign breast disease (6.4%, P = 0.011). The concentrations of circulating SOX2-Abs were found to discriminate between breast cancer patients and healthy controls (P < 0.001) and between breast cancer patients and those with benign breast disease (P < 0.001). In addition, measurement of SOX2-Abs was more effective than assays of serum tissue polypeptide-specific antigen, carcinoembryonic antigen, carbohydrate antigen (CA) 125, and CA 15-3 in distinguishing between malignant and benign breast disease. In breast cancer patients, the prevalence of SOX2-Abs was associated with a higher tumor grade (P = 0.021) and positive nodal status (P = 0.021).

Conclusion: The presence of SOX2-Abs in breast cancer may be of clinical value.

Impact: This study provides the first evidence for the presence of circulating SOX2-Abs in breast cancer and shows their potential clinical application. Cancer Epidemiol Biomarkers Prev; 21(11); 2043–7. ©2012 AACR.
Interpretation of Single and Serial Measures of HE4 and CA125 in Asymptomatic Women at High Risk for Ovarian Cancer
Authors: Urban Nicole , Thorpe Jason , Karlan Beth Y. , McIntosh Martin W. , Palomares Melanie R. , Daly Mary B. , Paley Pamela , Drescher Charles W.
Published: November 2012

Background: Human epididymis protein 4 (HE4) is approved for clinical use with CA125 to predict epithelial ovarian cancer in women with a pelvic mass or in remission after chemotherapy. Previously reported reference ranges for HE4 are inconsistent.

Methods: We report positivity thresholds yielding 90%, 95%, 98%, and 99% specificity for age-defined populations of healthy women for HE4, CA125, and Risk of Ovarian Malignancy Algorithm (ROMA), a weighted average of HE4 and CA125. HE4 and CA125 were measured in 1,780 samples from 778 healthy women aged >25 years with a documented deleterious mutation, or aged >35 years with a significant family history. Effects on marker levels of a woman's age, ethnicity, and epidemiologic characteristics were estimated, as were the population-specific means, variances, and within- and between-woman variances used to generate longitudinal screening algorithms for these markers.

Results: CA125 levels were lower with Black ethnicity (P = 0.008). Smoking was associated with higher HE4 (P = 0.007) and ROMA (P < 0.019). Continuous oral contraceptive use decreased levels of CA125 (P = 0.041), and ROMA (P = 0.12). CA125 was lower in women age ≥55, and HE4 increased with age (P < 0.01), particularly among women age ≥55.

Conclusions: Because of the strong effect of age on HE4, thresholds for HE4 are best defined for women of specific ages. Age-specific population thresholds for HE4 for 95% specificity ranged from 41.4 pmol/L for women age 30 to 82.1 pmol/L for women age 80.

Impact: Incorporation of serial marker values from screening history reduces personalized thresholds for CA125 and HE4 but is inappropriate for ROMA. Cancer Epidemiol Biomarkers Prev; 21(11); 2087–94. ©2012 AACR.
Mental and Physical Health–Related Quality of Life among U.S. Cancer Survivors: Population Estimates from the 2010 National Health Interview Survey
Authors: Weaver Kathryn E. , Forsythe Laura P. , Reeve Bryce B. , Alfano Catherine M. , Rodriguez Juan L. , Sabatino Susan A. , Hawkins Nikki A. , Rowland Julia H.
Published: November 2012

Background: Despite extensive data on health-related quality of life (HRQOL) among cancer survivors, we do not yet have an estimate of the percentage of survivors with poor mental and physical HRQOL compared with population norms. HRQOL population means for adult-onset cancer survivors of all ages and across the survivorship trajectory also have not been published.

Methods: Survivors (N = 1,822) and adults with no cancer history (N = 24,804) were identified from the 2010 National Health Interview Survey. The PROMIS® Global Health Scale was used to assess HRQOL. Poor HRQOL was defined as 1 SD or more below the PROMIS® population norm.

Results: Poor physical and mental HRQOL were reported by 24.5% and 10.1% of survivors, respectively, compared with 10.2% and 5.9% of adults without cancer (both P < 0.0001). This represents a population of approximately 3.3 million and 1.4 million U.S. survivors with poor physical and mental HRQOL. Adjusted mean mental and physical HRQOL scores were similar for breast, prostate, and melanoma survivors compared with adults without cancer. Survivors of cervical, colorectal, hematologic, short-survival, and other cancers had worse physical HRQOL; cervical and short-survival cancer survivors reported worse mental HRQOL.

Conclusion: These data elucidate the burden of cancer diagnosis and treatment among U.S. survivors and can be used to monitor the impact of national efforts to improve survivorship care and outcomes.

Impact: We present novel data on the number of U.S. survivors with poor HRQOL. Interventions for high-risk groups that can be easily implemented are needed to improve survivor health at a population level. Cancer Epidemiol Biomarkers Prev; 21(11); 2108–17. ©2012 AACR.
Patterns of Bone Sarcomas as a Second Malignancy in Relation to Radiotherapy in Adulthood and Histologic Type
Authors: Wu Lindsey C. , Kleinerman Ruth A. , Curtis Rochelle E. , Savage Sharon A. , de González Amy Berrington
Published: November 2012

Background: Radiotherapy decreases cancer mortality, but is associated with an increased incidence of second primary cancers, including osteosarcomas, especially after exposure in childhood. It remains uncertain whether radiation is related to other histologic types of bone sarcomas such as chondrosarcomas that are more common in adulthood.

Methods: Using data from 1973 to 2008 Surveillance Epidemiology and End Results registries, we evaluated long-term risk of bone cancer in 1,284,537 adult 5-year cancer survivors. We used standardized incidence ratios (SIR) to compare second bone sarcoma rates to the general population for each histologic type. We also used multivariate Poisson regression to estimate the relative risk (RR) associated with radiotherapy for the most common subtypes, osteosarcoma and chondrosarcoma.

Results: By the end of 2008, 159 second bone sarcomas were reported. Compared with the general population, the risk of developing any bone sarcoma was increased by 25% in patients with no history of radiotherapy [Observed (O) = 89, SIR = 1.25 (1.00–1.54)] and by 257% in patients with a history of radiotherapy [O = 70, SIR = 3.57 (2.78–4.50)]. For each histologic subtype, SIRs were higher among patients who had previously received radiotherapy than among those who had not. The RR for radiotherapy for osteosarcoma (n = 63) was 5.08 (3.05–8.59) and for chondrosarcoma (n = 69) was 1.54 (0.88–2.59), and these risks were even greater for second sarcomas that arose in the radiotherapy field used to treat the first cancer [osteosarcoma, RR = 10.35 (4.96–23.66); chondrosarcoma RR = 8.21 (2.09–39.89)].

Conclusions: Our findings provide the first evidence of a likely association between radiation exposure and chondrosarcoma.

Impact: These results further our understanding of radiotherapy-related cancer risks and will potentially direct practices in long-term surveillance of cancer survivors. Cancer Epidemiol Biomarkers Prev; 21(11); 1993–9. ©2012 AACR.
Results of a Randomized Controlled Trial Testing the Efficacy of a Culturally Targeted and a Generic Video on Mammography Screening among Chinese-American Immigrants
Authors: Wang Judy Huei-yu , Schwartz Marc D. , Brown Roger L. , Maxwell Annette E. , Lee Marion M. , Adams Inez F. , Mandelblatt Jeanne S.
Published: November 2012

Background: Research comparing the effects of culturally targeted and generic but linguistically appropriate intervention programs is limited. We conducted a randomized controlled trial comparing the efficacy of a culturally targeted video, a generic video, and a fact sheet (control) in promoting mammography screening among Chinese-American immigrants.

Methods: We randomized 664 Chinese-American women from the Washington, DC, and New York City areas who were older than 40 years and nonadherent to annual mammography screening guidelines to three study arms (each with ∼221 women). The outcome was self-reported mammography screening 6 months post intervention. Measures of knowledge, Eastern cultural views, and health beliefs were administered before and after the intervention.

Results: The culturally targeted video, the generic video, and the fact sheet increased mammography use by 40.3%, 38.5%, and 31.1% from baseline, respectively. A significant intervention effect was observed only in one subgroup: The culturally targeted video significantly increased mammography screening among low-acculturated women over the fact sheet [OR, 1.70; 95% confidence interval (CI), 1.04–2.78]. Overall, women who obtained a mammogram during the follow-up period reported significantly fewer barriers to screening after intervention than those who had not obtained screening. Both of the video groups reported fewer barriers after intervention than the control group.

Conclusions: Both theoretically guided videos increased the likelihood of mammography use to a similar extent. Cultural targeting was only effective for low-acculturated women. Both videos reduced perceived barriers to screening and consequently increased screening behavior.

Impact: The results of this study provide empirical evidence on the efficacy of cultural targeting for minority immigrants. Cancer Epidemiol Biomarkers Prev; 21(11); 1923–32. ©2012 AACR.
A Recombinant Immunotoxin against the Tumor-Associated Antigen Mesothelin Reengineered for High Activity, Low Off-Target Toxicity, and Reduced Antigenicity
Authors: Weldon John E. , Xiang Laiman , Zhang Jingli , Beers Richard , Walker Dawn A. , Onda Masanori , Hassan Raffit , Pastan Ira
Published: November 2012

SS1P is a recombinant immunotoxin (RIT) engineered for the targeted elimination of malignant cells that express the tumor-associated antigen mesothelin. It is composed of an antimesothelin antibody variable fragment (Fv) linked to a cytotoxic fragment of Pseudomonas exotoxin A (PE) that includes domains II and III of native PE. The clinical use of SS1P is limited by its propensity to induce neutralizing antibodies and to cause a dose-limiting capillary leak syndrome (CLS) in patients. In this article, we describe a reengineered SS1P with improved properties that overcome these deficits. The redesign of SS1P consists of (i) removing the bulk of PE domain II (residues 251–273 and 284–394 of native PE), leaving only an 11-residue furin cleavage site, (ii) adding a Gly–Gly–Ser peptide linker after the furin cleavage site, and (iii) replacing eight highly solvent-exposed residues in the catalytic domain of PE. The new molecule, SS1-LR/GGS/8M, has cytotoxic activity comparable with SS1P on several mesothelin-expressing cell lines and remarkably improved activity on primary cells from patients with mesothelioma. In a mouse xenograft tumor model, high doses of SS1-LR/GGS/8M elicit antitumor activity superior to the activity of SS1P at its maximum-tolerated dose. In addition, SS1-LR/GGS/8M has greatly decreased ability to cause CLS in a rat model and reduced antigenicity or reactivity with antibodies to the sera of patients previously treated with SS1P. Mol Cancer Ther; 12(1); 48–57. ©2012 AACR.
How Small Is Too Small? A Systematic Review of Center Volume and Outcome After Cardiac Transplantation
Authors: Pettit Stephen J. , Jhund Pardeep S. , Hawkins Nathaniel M. , Gardner Roy S. , Haj-Yahia Saleem , McMurray John J.V. , Petrie Mark C.
Published: November 2012

Background—

The aim of this study was to assess the relationship between the volume of cardiac transplantation procedures performed in a center and the outcome after cardiac transplantation.

Methods and Results—

PubMed, Embase, and the Cochrane library were searched for articles on the volume–outcome relationship in cardiac transplantation. Ten studies were identified, and all adopted a different approach to data analysis and varied in adjustment for baseline characteristics. The number of patients in each study ranged from 798 to 14401, and observed 1-year mortality ranged from 12.6% to 34%. There was no association between the continuous variables of center volume and observed mortality. There was a weak association between the continuous variables of center volume and adjusted mortality up to 1 year and a stronger association at 5 years. When centers were grouped in volume categories, low-volume centers had the highest adjusted mortality, intermediate-volume centers had lower adjusted mortality, and high-volume centers had the lowest adjusted mortality but were not significantly better than intermediate-volume centers. Category limits were arbitrary and varied between studies.

Conclusions—

There is a relationship between center volume and mortality in heart transplantation. The existence of a minimum acceptable center volume or threshold is unproven. However, a level of 10 to 12 heart transplants per year corresponds to the upper limit of low-volume categories that may have relatively higher mortality. It is not known whether outcomes for patients treated in low-volume transplant centers would be improved by reorganizing centers to ensure volumes in excess of 10 to 12 heart transplants per year.
Mechanism of Loss of Kv11.1 K
+
Current in Mutant T421M-Kv11.1–Expressing Rat Ventricular Myocytes
Authors: Balijepalli Sadguna Y. , Lim Evi , Concannon Sarah P. , Chew Chen L. , Holzem Kassandra E. , Tester David J. , Ackerman Michael J. , Delisle Brian P. , Balijepalli Ravi C. , January Craig T.
Published: November 2012

Background—

Type 2 long QT syndrome involves mutations in the human ether a-go-go–related gene (
hERG
or
KCNH2
). T421M, an S1 domain mutation in the Kv11.1 channel protein, was identified in a resuscitated patient. We assessed its biophysical, protein trafficking, and pharmacological mechanisms in adult rat ventricular myocytes.

Methods and Results—

Isolated adult rat ventricular myocytes were infected with wild-type (WT)–Kv11.1– and T421M-Kv11.1–expressing adenovirus and analyzed with the use of patch clamp, Western blot, and confocal imaging techniques. Expression of WT-Kv11.1 or T421M-Kv11.1 produced peak tail current (
I
Kv11.1
) of 8.78±1.18 and 1.91±0.22 pA/pF, respectively. Loss of mutant
I
Kv11.1
resulted from (1) a partially trafficking-deficient channel protein with reduced cell surface expression and (2) altered channel gating with a positive shift in the voltage dependence of activation and altered kinetics of activation and deactivation. Coexpression of WT+T421M-Kv11.1 resulted in heterotetrameric channels that remained partially trafficking deficient with only a minimal increase in peak
I
Kv11.1
density, whereas the voltage dependence of channel gating became WT-like. In the adult rat ventricular myocyte model, both WT-Kv11.1 and T421M-Kv11.1 channels responded to β-adrenergic stimulation by increasing
I
Kv11.1
.

Conclusions—

The T421M-Kv11.1 mutation caused a loss of
I
Kv11.1
through interactions of abnormal protein trafficking and channel gating. Furthermore, for coexpressed WT+T421M-Kv11.1 channels, different dominant-negative interactions govern protein trafficking and ion channel gating, and these are likely to be reflected in the clinical phenotype. Our results also show that WT and mutant Kv11.1 channels responded to β-adrenergic stimulation.
Effects of Interleukin-1β Inhibition With Canakinumab on Hemoglobin A1c, Lipids, C-Reactive Protein, Interleukin-6, and Fibrinogen
Authors: Ridker Paul M , Howard Campbell P. , Walter Verena , Everett Brendan , Libby Peter , Hensen Johannes , Thuren Tom
Published: November 2012

Background—

To test formally the inflammatory hypothesis of atherothrombosis, an agent is needed that reduces inflammatory biomarkers such as C-reactive protein, interleukin-6, and fibrinogen but that does not have major effects on lipid pathways associated with disease progression.

Methods and Results—

We conducted a double-blind, multinational phase IIb trial of 556 men and women with well-controlled diabetes mellitus and high cardiovascular risk who were randomly allocated to subcutaneous placebo or to subcutaneous canakinumab at doses of 5, 15, 50, or 150 mg monthly and followed over 4 months. Compared with placebo, canakinumab had modest but nonsignificant effects on the change in hemoglobin A1c, glucose, and insulin levels. No effects were seen for low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or non–high-density lipoprotein cholesterol, although triglyceride levels increased ≈10% in the 50-mg (
P
=0.02) and 150-mg (
P
=0.03) groups. By contrast, the median reductions in C-reactive protein at 4 months were 36.4%, 53.0%, 64.6%, and 58.7% for the 5-, 15-, 50-, and 150-mg canakinumab doses, respectively, compared with 4.7% for placebo (all
P
values ≤0.02). Similarly, the median reductions in interleukin-6 at 4 months across the canakinumab dose range tested were 23.9%, 32.5%, 47.9%, and 44.5%, respectively, compared with 2.9% for placebo (all
P
≤0.008), and the median reductions in fibrinogen at 4 months were 4.9%, 11.7%, 18.5%, and 14.8%, respectively, compared with 0.4% for placebo (all
P
values ≤0.0001). Effects were observed in women and men. Clinical adverse events were similar in the canakinumab and placebo groups.

Conclusions—

Canakinumab, a human monoclonal antibody that neutralizes interleukin-1β, significantly reduces inflammation without major effect on low-density lipoprotein cholesterol or high-density lipoprotein cholesterol. These phase II trial data support the use of canakinumab as a potential therapeutic method to test directly the inflammatory hypothesis of atherosclerosis.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00900146.
Hypothermia in Comatose Survivors From Out-of-Hospital Cardiac Arrest
Authors: Lopez-de-Sa Esteban , Rey Juan R. , Armada Eduardo , Salinas Pablo , Viana-Tejedor Ana , Espinosa-Garcia Sandra , Martinez-Moreno Mercedes , Corral Ervigio , Lopez-Sendon Jose
Published: November 2012

Background—

It is recommended that comatose survivors of out-of-hospital cardiac arrest should be cooled to 32° to 34°C for 12 to 24 hours. However, the optimal level of cooling is unknown. The aim of this pilot study was to obtain initial data on the effect of different levels of hypothermia. We hypothesized that deeper temperatures will be associated with better survival and neurological outcome.

Methods and Results—

Patients were eligible if they had a witnessed out-of-hospital cardiac arrest from March 2008 to August 2011. Target temperature was randomly assigned to 32°C or 34°C. Enrollment was stratified on the basis of the initial rhythm as shockable or asystole. The target temperature was maintained during 24 hours followed by 12 to 24 hours of controlled rewarming. The primary outcome was survival free from severe dependence (Barthel Index score ≥60 points) at 6 months. Thirty-six patients were enrolled in the trial (26 shockable rhythm, 10 asystole), with 18 assigned to 34°C and 18 to 32°C. Eight of 18 patients in the 32°C group (44.4%) met the primary end point compared with 2 of 18 in the 34°C group (11.1%) (log-rank
P
=0.12). All patients whose initial rhythm was asystole died before 6 months in both groups. Eight of 13 patients with initial shockable rhythm assigned to 32°C (61.5%) were alive free from severe dependence at 6 months compared with 2 of 13 (15.4%) assigned to 34°C (log-rank
P
=0.029). The incidence of complications was similar in both groups except for the incidence of clinical seizures, which was lower (1 versus 11;
P
=0.0002) in patients assigned to 32°C compared with 34°C. On the contrary, there was a trend toward a higher incidence of bradycardia (7 versus 2;
P
=0.054) in patients assigned to 32°C. Although potassium levels decreased to a greater extent in patients assigned to 32°C, the incidence of hypokalemia was similar in both groups.

Conclusions—

The findings of this pilot trial suggest that a lower cooling level may be associated with a better outcome in patients surviving out-of-hospital cardiac arrest secondary to a shockable rhythm. The benefits observed here merit further investigation in a larger trial in out-of-hospital cardiac arrest patients with different presenting rhythms.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01155622.
Miraculous Agitations: On the Uses of Chaotic, Non-Linear and Emergent Behavior in Acoustic Vibrating Physical Systems
Authors: Wilson Daniel
Published: November 2012

“Miraculous agitation” denotes an acoustic marvel: a striking sound emerging from vibrating physical systems. A somewhat subjective phenomenon, acoustic marvels are typified by expressive or harmonic richness, and their production is reliant on delicate interrelationships between objects under vibration, often involving chaotic or nonlinear behavior. In some cases it is even possible to observe emergent behavior. Significantly, acoustic marvels may commonly strike the auditor as seeming to be “of electronic origin,” thus pointing toward postelectronic electroacoustic techniques. This paper takes a qualitative approach to the examination of such acoustic marvels and their possible applications in new music composition.
Organ of Corti: A Listening Device
Authors: Prior David
Published: November 2012

The author discusses a piece that recycles noise in the surrounding environment, inviting active listening and contemplation on the act of listening itself.
Acoustic Mirage: A Psychoacoustic Sound Installation
Authors: Band Ellen
Published: November 2012

The author describes her creation of a sound installation inspired by the phenomenon of auditory hallucinations.
A Global Climatology of Tropical Moisture Exports
Authors: Knippertz Peter , Wernli Heini , Gläser Gregor
Published: November 2012

In a recent paper, a climatology of tropical moisture exports (TMEs) to the Northern Hemisphere (NH) was constructed on the basis of 7-day forward trajectories, started daily from the tropical lower troposphere, which were required to reach a water vapor flux of at least 100 g kg−1 m s−1 somewhere north of 35°N. It was shown that TMEs contribute significantly to regional precipitation. Here, the authors complement and extend this work by (i) using 6-hourly European Centre for Medium-Range Weather Forecasts (ECMWF) Interim Re-Analysis (ERA-Interim) data from 1979 to 2010 instead of the earlier 40-yr ECMWF Re-Analysis (ERA-40), (ii) extending the climatology to the Southern Hemisphere (SH), and (iii) relating TME events to atmospheric rivers (ARs) previously discussed in the literature. The main conclusions are as follows: First, the TME climatology is not sensitive to the reanalysis dataset. Second, SH TME shows four activity centers: the central and eastern Pacific Ocean (170°–90°W, near the South Pacific convergence zone), eastern South America and the adjacent Atlantic Ocean (60°W–0°, near the South Atlantic convergence zone), the western Indian Ocean (30°–80°E), and western Australia (110°–140°E). Third, TME activity in the SH peaks in austral summer because of higher moisture contents and possibly because of increased Rossby wave activity from the NH. Fourth, El Niño warm events are associated with reduced activity over the South Pacific and increased activity over the South Atlantic and around Australia, while correlations with the southern annular mode are generally weak. Finally, around 90% of all ARs affecting the U.S. West Coast during December–May are connected to TME events, revealing their importance for heavy rain and flooding.
A Theoretical Explanation of the Fetch- and Duration-Limited Laws
Authors: Fontaine Emmanuel
Published: November 2012

The evolution of wind-induced ocean waves is studied theoretically. The modeling assumes that wave groups evolve independently of each other in a state of local equilibrium between wind-pumping- and wave-breaking-induced dissipation. The well-known fetch and duration laws appear as natural solutions of the model in the case of a constant wind speed. The link between the fetch and duration laws is explained, and the results are successfully validated against various experimental data.
Impact of Breaking Wave Form Drag on Near-Surface Turbulence and Drag Coefficient over Young Seas at High Winds
Authors: Suzuki Nobuhiro , Hara Tetsu , Sullivan Peter P.
Published: November 2012

The effects of breaking waves on near-surface wind turbulence and drag coefficient are investigated using large-eddy simulation. The impact of intermittent and transient wave breaking events (over a range of scales) is modeled as localized form drag, which generates airflow separation bubbles downstream. The simulations are performed for very young sea conditions under high winds, comparable to previous laboratory experiments in hurricane-strength winds. The results for the drag coefficient in high winds range between about 0.002 and 0.003. In such conditions more than 90% of the total air–sea momentum flux is due to the form drag of breakers; that is, the contributions of the nonbreaking wave form drag and the surface viscous stress are small. Detailed analysis shows that the breaker form drag impedes the shear production of the turbulent kinetic energy (TKE) near the surface and, instead, produces a large amount of small-scale wake turbulence by transferring energy from large-scale motions (such as mean wind and gusts). This process shortcuts the inertial energy cascade and results in large TKE dissipation (integrated over the surface layer) normalized by friction velocity cubed. Consequently, the large production of wake turbulence by breakers in high winds results in the small drag coefficient obtained in this study. The results also suggest that common parameterizations for the mean wind profile and the TKE dissipation inside the wave boundary layer, used in previous Reynolds-averaged Navier–Stokes models, may not be valid.
Implicit Particle Methods and Their Connection with Variational Data Assimilation
Authors: Atkins Ethan , Morzfeld Matthias , Chorin Alexandre J.
Published: November 2012

The implicit particle filter is a sequential Monte Carlo method for data assimilation that guides the particles to the high-probability regions via a sequence of steps that includes minimizations. A new and more general derivation of this approach is presented and the method is extended to particle smoothing as well as to data assimilation for perfect models. Minimizations required by implicit particle methods are shown to be similar to those that one encounters in variational data assimilation, and the connection of implicit particle methods with variational data assimilation is explored. In particular, it is argued that existing variational codes can be converted into implicit particle methods at a low additional cost, often yielding better estimates that are also equipped with quantitative measures of the uncertainty. A detailed example is presented.
Predictability of a Mediterranean Tropical-Like Storm Downstream of the Extratropical Transition of Hurricane Helene (2006)
Authors: Pantillon Florian P. , Chaboureau Jean-Pierre , Mascart Patrick J. , Lac Christine
Published: November 2012

The extratropical transition (ET) of a tropical cyclone is known as a source of forecast uncertainty that can propagate far downstream. The present study focuses on the predictability of a Mediterranean tropical-like storm (Medicane) on 26 September 2006 downstream of the ET of Hurricane Helene from 22 to 25 September. While the development of the Medicane was missed in the deterministic forecasts from the European Centre for Medium-Range Weather Forecasts (ECMWF) initialized before and during ET, it was contained in the ECMWF ensemble forecasts in more than 10% of the 50 members up to 108-h lead time. The 200 ensemble members initialized at 0000 UTC from 20 to 23 September were clustered into two nearly equiprobable scenarios after the synoptic situation over the Mediterranean. In the first and verifying scenario, Helene was steered northeastward by an upstream trough during ET and contributed to the building of a downstream ridge. A trough elongated farther downstream toward Italy and enabled the development of the Medicane in 9 of 102 members. In the second and nonverifying scenario, Helene turned southeastward during ET and the downstream ridge building was reduced. A large-scale low over the British Isles dominated the circulation in Europe and only 1 of 98 members forecasted the Medicane. The two scenarios resulted from a different phasing between Helene and the upstream trough. Sensitivity experiments performed with the Méso-NH model further revealed that initial perturbations targeted on Helene and the upstream trough were sufficient in forecasting the warm-core Medicane at 84- and 108-h lead time.