bluuebunny/crossref_metadata_2025 huggingface dataset:
YM155 Reverses Cisplatin Resistance in Head and Neck Cancer by Decreasing Cytoplasmic Survivin Levels
Authors: Kumar Bhavna , Yadav Arti , Lang James C. , Cipolla Michael J. , Schmitt Alessandra C. , Arradaza Nicole , Teknos Theodoros N. , Kumar Pawan
Published: June 2012

Cisplatin is one of the commonly used chemotherapeutic drugs for the treatment of head and neck squamous cell carcinoma (HNSCC). However, acquisition of cisplatin resistance is common in patients with HNSCC, and it often leads to local and distant failure. In this study, we showed that survivin expression is significantly upregulated in HNSCC primary tumors and cell lines. In addition, survivin levels were significantly higher in human papilloma virus–negative patients that normally respond poorly to cisplatin treatment. Survivin expression was further increased in cisplatin-resistant cells (CAL27-CisR) as compared with its parent cells (CAL27). Therefore, we hypothesized that targeting of survivin in HNSCC could reverse the resistant phenotype in tumor cells, thereby enhancing the therapeutic efficacy of cisplatin. We used both in vitro and in vivo models to test the efficacy of YM155, a small molecule survivin inhibitor, either as a single agent or in combination with cisplatin. YM155 significantly decreased survivin levels and cell proliferation in a dose-dependent manner. In addition, YM155 pretreatment significantly reversed cisplatin resistance in cancer cells. Interestingly, YM155 treatment altered the dynamic localization of survivin in cells by inducing a rapid reduction in cytoplasmic survivin, which plays a critical role in its antiapoptotic function. In a severe combined immunodeficient mouse xenograft model, YM155 significantly enhanced the antitumor and antiangiogenic effects of cisplatin, with no added systemic toxicity. Taken together, our results suggest a potentially novel strategy to use YM155 to overcome the resistance in tumor cells, thereby enhancing the effectiveness of the chemotherapy in HNSCC. Mol Cancer Ther; 11(9); 1988–98. ©2012 AACR.
Identification of Genomic Targets of Transcription Factor Aebp1 and its role in Survival of Glioma Cells
Authors: Ladha Jayashree , Sinha Swati , Bhat Vasudeva , Donakonda Sainitin , Rao Satyanarayana M.R.
Published: June 2012

A recent transcriptome analysis of graded patient glioma samples led to identification of AEBP1 as one of the genes upregulated in majority of the primary GBM as against secondary GBM. Aebp1 is a transcriptional repressor that is involved in adipogenesis. It binds to AE-1 element present in the proximal promoter of aP2 gene that codes for fatty acid binding protein (FABP4). A comprehensive study was undertaken to elucidate the role of AEBP1 overexpression in glioblastoma. We employed complementary gene silencing approach to identify the genes that are perturbed in a glioma cell line (U87MG). A total of 734 genes were differentially regulated under these conditions (≥1.5-fold, P ≤ 0.05) belonging to different GO categories such as transcription regulation, cell growth, proliferation, differentiation, and apoptosis of which perturbation of 114 genes of these pathways were validated by quantitative real time PCR (qRT-PCR). This approach was subsequently combined with ChIP-chip technique using an Agilent human promoter tiling array to identify genomic binding loci of Aebp1 protein. A subset of these genes identified for Aebp1 occupancy was also validated by ChIP-PCR. Bioinformatics analysis of the promoters identified by ChIP-chip technique revealed a consensus motif GAAAT present in 66% of the identified genes. This consensus motif was experimentally validated by functional promoter assay using luciferase as the reporter gene. Both cellular proliferation and survival were affected in AEBP1-silenced U87MG and U138MG cell lines and a significant percentage of these cells were directed towards apoptosis. Mol Cancer Res; 10(8); 1039–51. ©2012 AACR.
Bioenergetic and Functional Consequences of Cellular Therapy
Authors: Xiong Qiang , Ye Lei , Zhang Pengyuan , Lepley Michael , Swingen Cory , Zhang Liying , Kaufman Dan S. , Zhang Jianyi
Published: June 2012

Rationale:

The mechanism by which endogenous progenitor cells contribute to functional and beneficial effects in stem cell therapy remains unknown.

Objective:

Utilizing a novel
31
P magnetic resonance spectroscopy–2-dimensional chemical shift imaging method, this study examined the heterogeneity and bioenergetic consequences of postinfarction left ventricular (LV) remodeling and the mechanisms of endogenous progenitor cell contribution to the cellular therapy.

Methods and Results:

Human embryonic stem cell–derived vascular cells (hESC-VCs) that stably express green fluorescent protein and firefly luciferase (GFP
+
/Luc
+
) were used for the transplantation. hESC-VCs may release various cytokines to promote angiogenesis, prosurvival, and antiapoptotic effects. Both in vitro and in vivo experiments demonstrated that hESC-VCs effectively inhibit myocyte apoptosis. In the mouse model, a fibrin patch–based cell delivery resulted in a significantly better cell engraftment rate that was accompanied by a better ejection fraction. In the swine model of ischemia-reperfusion, the patch-enhanced delivery of hESC-VCs resulted in alleviation of abnormalities including border zone myocardial perfusion, contractile dysfunction, and LV wall stress. These results were also accompanied by a pronounced recruitment of endogenous c-kit
+
cells to the injury site. These improvements were directly associated with a remarkable improvement in myocardial energetics, as measured by a novel in vivo
31
P magnetic resonance spectroscopy–2-dimensional chemical shift imaging technology.

Conclusions:

The findings of this study demonstrate that a severely abnormal heterogeneity of myocardial bioenergetics in hearts with postinfarction LV remodeling can be alleviated by the hESC-VCs therapy. These findings suggest an important therapeutic target of peri-scar border zone and a promising therapeutic potential for using hESC-VCs together with the fibrin patch–based delivery system.
Functional Na
V
1.8 Channels in Intracardiac Neurons
Authors: Verkerk Arie O. , Remme Carol Ann , Schumacher Cees A. , Scicluna Brendon P. , Wolswinkel Rianne , de Jonge Berend , Bezzina Connie R. , Veldkamp Marieke W.
Published: June 2012

Rationale:

The
SCN10A
gene encodes the neuronal sodium channel isoform Na
V
1.8. Several recent genome-wide association studies have linked
SCN10A
to PR interval and QRS duration, strongly suggesting an as-yet unknown role for Na
V
1.8 in cardiac electrophysiology.

Objective:

To demonstrate the functional presence of
SCN10A
/Nav1.8 in intracardiac neurons of the mouse heart.

Methods and Results:

Immunohistochemistry on mouse tissue sections showed intense Na
V
1.8 labeling in dorsal root ganglia and intracardiac ganglia and only modest Na
V
1.8 expression within the myocardium. Immunocytochemistry further revealed substantial Na
V
1.8 staining in isolated neurons from murine intracardiac ganglia but no Na
V
1.8 expression in isolated ventricular myocytes. Patch-clamp studies demonstrated that the Na
V
1.8 blocker A-803467 (0.5–2 μmol/L) had no effect on either mean sodium current (I
Na
) density or I
Na
gating kinetics in isolated myocytes but significantly reduced I
Na
density in intracardiac neurons. Furthermore, A-803467 accelerated the slow component of current decay and shifted voltage dependence of inactivation toward more negative voltages, as expected for blockade of Na
V
1.8-based I
Na
. In line with these findings, A-803467 did not affect cardiomyocyte action potential upstroke velocity but markedly reduced action potential firing frequency in intracardiac neurons, confirming a functional role for Na
V
1.8 in cardiac neural activity.

Conclusions:

Our findings demonstrate the functional presence of
SCN10A
/Na
V
1.8 in intracardiac neurons, indicating a novel role for this neuronal sodium channel in regulation of cardiac electric activity.
Prediction of Progression of Coronary Artery Disease and Clinical Outcomes Using Vascular Profiling of Endothelial Shear Stress and Arterial Plaque Characteristics
Authors: Stone Peter H. , Saito Shigeru , Takahashi Saeko , Makita Yasuhiro , Nakamura Shigeru , Kawasaki Tomohiro , Takahashi Akihiko , Katsuki Takaaki , Nakamura Sunao , Namiki Atsuo , Hirohata Atsushi , Matsumura Toshiyuki , Yamazaki Seiji , Yokoi Hiroyoshi , Tanaka Shinji , Otsuji Satoru , Yoshimachi Fuminobu , Honye Junko , Harwood Dawn , Reitman Martha , Coskun Ahmet U. , Papafaklis Michail I. , Feldman Charles L.
Published: June 2012

Background—

Atherosclerotic plaques progress in a highly individual manner. The purposes of the Prediction of Progression of Coronary Artery Disease and Clinical Outcome Using Vascular Profiling of Shear Stress and Wall Morphology (PREDICTION) Study were to determine the role of local hemodynamic and vascular characteristics in coronary plaque progression and to relate plaque changes to clinical events.

Methods and Results—

Vascular profiling, using coronary angiography and intravascular ultrasound, was used to reconstruct each artery and calculate endothelial shear stress and plaque/remodeling characteristics in vivo. Three-vessel vascular profiling (2.7 arteries per patient) was performed at baseline in 506 patients with an acute coronary syndrome treated with a percutaneous coronary intervention and in a subset of 374 (74%) consecutive patients 6 to 10 months later to assess plaque natural history. Each reconstructed artery was divided into sequential 3-mm segments for serial analysis. One-year clinical follow-up was completed in 99.2%. Symptomatic clinical events were infrequent: only 1 (0.2%) cardiac death; 4 (0.8%) patients with new acute coronary syndrome in nonstented segments; and 15 (3.0%) patients hospitalized for stable angina. Increase in plaque area (primary end point) was predicted by baseline large plaque burden; decrease in lumen area (secondary end point) was independently predicted by baseline large plaque burden and low endothelial shear stress. Large plaque size and low endothelial shear stress independently predicted the exploratory end points of increased plaque burden and worsening of clinically relevant luminal obstructions treated with a percutaneous coronary intervention at follow-up. The combination of independent baseline predictors had a 41% positive and 92% negative predictive value to predict progression of an obstruction treated with a percutaneous coronary intervention.

Conclusions—

Large plaque burden and low local endothelial shear stress provide independent and additive prediction to identify plaques that develop progressive enlargement and lumen narrowing.

Clinical Trial Registration—

URL:
http:www.//clinicaltrials.gov
. Unique Identifier: NCT01316159.
Kidney Function and White Matter Disease in Young Stroke Patients
Authors: Steinicke Robert , Gaertner Beate , Grittner Ulrike , Schmidt Wolf , Dichgans Martin , Heuschmann Peter U. , Tanislav Christian , Putaala Jukka , Kaps Manfred , Endres Matthias , Schmidt Reinhold , Fazekas Franz , Norrving Bo , Rolfs Arndt , Martus Peter , Tatlisumak Turgut , Enzinger Christian , Jungehulsing Gerhard Jan
Published: June 2012

Background and Purpose—

Impaired kidney function is thought to be associated with small vessel disease, outcome, and mortality in the general stroke population. Data are limited regarding young patients. The aim of this study was to investigate the association of kidney function and white matter hyperintensities (WMHs) in young patients with first ischemic stroke.

Methods—

We analyzed 2500 young (18–55 years) patients with first-ever ischemic stroke from the prospective observational Stroke in Young Fabry Patients (SIFAP1) study with available MRI data on WMH. Of these, 2009 had available data concerning estimated glomerular filtration rate (eGFR). Kidney function was expressed as eGFR by the Modification of Diet in Renal Disease method. Deep WMHs on MRI were classified by the Fazekas score. Multivariate analysis was performed using a regression model with random effects.

Results—

Mean eGFR was 96.7 mL/min in those with WMH Grade 0 to 1 (none to mild), 90.7 mL/min in WMH Grade 2 (moderate), and 89 mL/min in WMH Grade 3 (severe). Univariate analysis revealed WMH to be associated with age (
P
<0.001), hypertension (
P
<0.001), cardiovascular disease (
P
=0.015), overweight (body mass index >25 kg/m
2
;
P
=0.013), current smoking (
P
=0.044), and eGFR (
P
=0.009). In multivariate analysis, age, hypertension, and eGFR remained associated with WMH severity.

Conclusions—

In young patients with acute ischemic stroke, lower eGFR values in the normal range are associated with the presence of moderate to severe WMH.

Clinical Trial Registration—

URL:
http://clinicaltrials.gov
. Unique Identifier: NCT00414583.
Impacts of Different Types of El Niño on the East Asian Climate: Focus on ENSO Cycles
Authors: Yuan Yuan , Yang Song
Published: June 2012

Using multiple datasets and a partial correlation method, the authors analyze the different impacts of eastern Pacific (EP) and central Pacific (CP) El Niño on East Asian climate, focusing on the features from El Niño developing summer to El Niño decaying summer. Unlike the positive–negative–positive (+/−/+) anomalous precipitation pattern over East Asia and the equatorial Pacific during EP El Niño, an anomalous −/+/− rainfall pattern appears during CP El Niño. The anomalous dry conditions over southeastern China and the northwestern Pacific during CP El Niño seem to result from the anomalous low-level anticyclone over southern China and the South China Sea, which is located more westward than the Philippine Sea anticyclone during EP El Niño. The continuous anomalous sinking motion over southeastern China, as part of the anomalous Walker circulation associated with CP El Niño, also contributes to these dry conditions.

During the developing summer, the impact of CP El Niño on East Asian climate is more significant than the influence of EP El Niño. During the decaying summer, however, EP El Niño exerts a stronger influence on East Asia, probably due to the long-lasting anomalous warming over the tropical Indian Ocean accompanying EP El Niño.

Temperatures over portions of East Asia and the northwestern Pacific tend to be above normal during EP El Niño but below normal from the developing autumn to the next spring during CP El Niño. A possible reason is the weakened (enhanced) East Asian winter monsoon related to EP (CP) El Niño.
Experimental Evidence of the Kraichnan Scalar Spectrum at High Reynolds Numbers
Authors: Bogucki D. J. , Luo H. , Domaradzki J. A.
Published: June 2012

Measurements of horizontal temperature gradient spectra were carried out in a 25 m × 12 m × 3 m freshwater well mixed swimming pool. The associated flow Reynolds number was found to vary from 4 × 103 to 6 × 103. In all analyzed cases, at large wavenumbers k, the temperature gradient spectra exhibited behavior consistent with the Kraichnan spectral form: ~exp[−(6qk)1/2k] with constant . The measurements are in agreement with direct numerical simulations of a passive scalar flow with of Bogucki et al. and with recent experimental observations of Sanchez et al.
Langmuir Circulation: An Agent for Vertical Restratification?
Authors: Li Ke , Zhang Zhexuan , Chini Greg , Flierl Glenn
Published: June 2012

Comparably little is known about the impact of down-front-propagating surface waves on the stability of submesoscale lateral fronts in the ocean surface mixed layer. In this investigation, the stability of lateral fronts in gradient–wind balance to two-dimensional (down-front invariant) disturbances is analyzed using the stratified, rotating Craik–Leibovich (CL) equations. Through the action of the CL vortex force, the surface waves fundamentally alter the superinertial, two-dimensional linear stability of these fronts, with the classical symmetric instability mode being replaced by a hybrid Langmuir circulation/symmetric mode. The hybrid mode is shown to exhibit much larger growth rates than the pure symmetric mode, to exist in a regime in which the vertical Richardson number is greater than 1, and to accomplish significant cross-isopycnal transport. Nonhydrostatic numerical simulations reveal that the nonlinear evolution of this hybrid instability mode can lead to rapid, that is, superinertial, vertical restratification of the mixed layer. Paradoxically, Langmuir circulation—generally viewed as a prominent vertical mixing mechanism in the upper ocean—may thus play a role in mixed layer restratification.
Retracted: Monitoring of water vapor variability using GPS during an El Niño event along the northern coast of Borneo Island
Authors: Suparta W.
Published: June 2012

The paper by W. Suparta "Monitoring of water vapor variability using GPS during an El Niño event along the northern coast of Borneo Island," has been withdrawn by the author prior to formal publication.
Interdisciplinary Climate: The Case of the First 50 Years of British Observations in Australia
Authors: McGuffie Kendal , Henderson-Sellers Ann
Published: June 2012

This paper presents the case for improved interdisciplinarity in climate research in the context of assessing and discussing the caution required when utilizing some types of historical climate data. This is done by a case study examining the reliability of the instruments used for collecting weather data in Australia between 1788 and 1840, as well as the observers themselves, during the British settlement of New South Wales. This period is challenging because the instruments were not uniformly calibrated and were created, repaired, and used by a wide variety of people with skills that frequently remain undocumented. Continuing significant efforts to rescue such early instrumental records of climate are likely to be enhanced by more open, interdisciplinary research that encourages discussion of an apparent dichotomy of view about the quantitative value of early single-instrument data between historians of physics (including museum curators) and climate researchers.
Transformations in the healthcare system in China
Authors: Lin Vivian
Published: June 2012

In April 2009, the Chinese government announced comprehensive reforms to the health system following more than a decade of piecemeal reform efforts. Popular complaints about high healthcare costs and access difficulties eventually received political attention following the government administration change of 2002 and the SARS outbreak of 2003. However, policy differences between ministries resulted in several years of vigorous and open policy debates involving domestic and international stakeholders as well as citizens who are active in expressing opinions virtually (netizens). The 2009 reforms signalled not only policy recognition of the need for a comprehensive and systemic approach if healthcare was to be transformed, but also charted new approaches to policy-making. While the current reforms are being rapidly implemented, the question arises as to whether the shifts in the policy-making process will continue into the future. Further evaluation of the policy process will require cooperation if not collaboration from the policy actors themselves.
‘Mutual aid’ beyond formal institutions: Integrated home care in Japan
Authors: Matsushige Takuya , Tsuisui Takako , Otaga Masaaki
Published: June 2012

The Japanese government has promoted the development of a home care system that integrates the provision of health and social care services and links formal and informal care. Yet the coordination of different forms of care faces a number of challenges. This article introduces a micro-sociological approach focusing on the relevance of ‘mutual aid’ in local communities as a guide to practical action. The article explores interactions, communication and coordination in multidisciplinary care delivery using a qualitative approach focusing on a region of the country with advanced integrated home care as a case study. The findings highlight the relevance of ‘mutual aid’ for integrated home care. The article concludes that health policy needs to establish incentives that enable collaboration across the formal–informal division of care.
A Multisite Study of Learning in Introductory Psychology Courses
Authors: Gurung Regan A. R. , Daniel David B. , Landrum R. Eric
Published: June 2012

Four hundred and fifty-four students enrolled in introductory psychology at different institutions across the nation participated in a study of factors related to learning. Key measures included an instructor rating, ratings of textbook quality and helpfulness, study time, student self-evaluations of study behaviors, approach to learning, self-report of learning, and a measure of quiz performance using biopsychology and learning chapter questions from a College Board Advanced Placement exam. The authors found significant predictors of both self-reported learning (deep approach, less surface approach, instructor ratings, student self-evaluations, and study behaviors) and quiz performance (grade point average, study time, metacognitive activity, and less use of a surface approach to learning). These results are discussed in the context of optimizing student learning and providing a foundation for future research.
Teaching Creativity
Authors: Simonton Dean Keith
Published: June 2012

In the past decade, the psychological study of creativity has accelerated greatly. To facilitate the teaching of creativity, I provide an overview of the recent literature. The overview begins by discussing recent empirical results and research trends. This discussion specifically treats creativity’s cognitive, differential, developmental, and social aspects. Then I outline central controversies in the study of creativity. These debates concern the nature of creative thought (domain-specific vs. generic processes), creative development (nature vs. nurture), and creative persons (psychopathology vs. mental health). The article closes by asking not just how to teach creativity but also how to teach creativity creatively.
Keeping Steady as She Goes: A Negotiated Order Perspective on Technological Evolution
Authors: Dokko Gina , Nigam Amit , Rosenkopf Lori
Published: June 2012

A central idea in the theory of technology cycles is that social and political mechanisms are most important during the selection of a dominant design, and that eras of incremental change are socially uninteresting periods in which innovation is driven by technological momentum and elaboration of the dominant design. In this essay, we overturn the ontological assumption that social order is inherently stable, drawing on Anselm Strauss’s concept of negotiated order to analyze the persistence of a dominant design as a social accomplishment: an outcome of ongoing processes that reinforce or challenge a socially negotiated order. Thus, we shift focus from battles over standards to periods of normal innovation. We extend the technology cycles model to explain social dynamics in periods of incremental change, and to make predictions specifying how contextual conditions in standards-setting organizations affect social interaction, leading to reinforcement or challenge to a socio-technical order.
The Quality of Planning Scholarship and Doctoral Education
Authors: Goldstein Harvey A.
Published: June 2012

The article links the nature of planning as a discipline, the quality of planning scholarship, and the training of our doctoral students in research methods. Deficiencies in research methods training that were identified by the Commission on the Doctorate in 1993 probably have not been ameliorated and may have expanded. A set of recommendations for the steps that doctoral programs could take to ameliorate the deficiencies are provided.
A thermodynamics-based homogeneous charge compression ignition engine model for adaptive nonlinear controller development
Authors: Bettis Joshua B , Massey Jeffery A , Drallmeier James A , Sarangapani Jagannathan
Published: June 2012

Low-temperature combustion modes, such as homogeneous charge compression ignition, represent a promising means to increase the efficiency and to reduce significantly the emissions of internal combustion engines. Implementation and control are difficult, however, owing to the dependence of the combustion event on the chemical kinetics rather than an external trigger. This work describes a nonlinear control-oriented model developed for a single-cylinder homogeneous charge compression ignition engine, which is physically based on a five-state thermodynamic cycle. This model is aimed at capturing the behavior of an engine which utilizes fully vaporized gasoline-type fuels, exhaust gas recirculation, and intake air heating in order to achieve homogeneous charge compression ignition operation. The onset of combustion, which is vital for control, is modeled using an Arrhenius reaction rate expression which relates the combustion timing to both the charge dilution and the temperature. Despite the fact that homogeneous charge compression ignition combustion is indeed fast, it is not perfectly instantaneous and therefore requires some finite amount of time to occur. To account for this phenomenon within the model, a Δθ term is added which shifts the point of instantaneous combustion from the start of combustion to a point of very-high-energy release based on experimental heat release data. The model is validated against experimental data from a single-cylinder compression ignition engine operating under homogeneous charge compression ignition conditions at two different fueling rates. Parameters relevant to control such as the combustion timing, peak in-cylinder pressure, and pressure rise rates from the simulation agree very well with the experiment in both operating conditions. The extension of the model to other fuels is also investigated via the octane index of several different gasoline-type fuels. Since this nonlinear model is developed from a controls perspective, both the output and the state update equations are formulated such that they are functions of only the control inputs and the state variables, therefore making them directly applicable to state-space methods for control. The result is a discrete-time nonlinear control model which provides a platform for developing and validating various nonlinear control strategies.
Causal inference with a quantitative exposure
Authors: Zhang Zhiwei , Zhou Jie , Cao Weihua , Zhang Jun
Published: June 2012

Summary

The current statistical literature on causal inference is mostly concerned with binary or categorical exposures, even though exposures of a quantitative nature are frequently encountered in epidemiologic research. In this article, we review the available methods for estimating the dose–response curve for a quantitative exposure, which include ordinary regression based on an outcome regression model, inverse propensity weighting and stratification based on a propensity function model, and an augmented inverse propensity weighting method that is doubly robust with respect to the two models. We note that an outcome regression model often imposes an implicit constraint on the dose–response curve, and propose a flexible modeling strategy that avoids constraining the dose–response curve. We also propose two new methods: a weighted regression method that combines ordinary regression with inverse propensity weighting and a stratified regression method that combines ordinary regression with stratification. The proposed methods are similar to the augmented inverse propensity weighting method in the sense of double robustness, but easier to implement and more generally applicable. The methods are illustrated with an obstetric example and compared in simulation studies.
Interracial Violence, Western Racialized Masculinities, and the Geopolitics of Violence Against Women
Authors: Park Hijin
Published: June 2012

This article examines violence against racialized women in North America and how this violence is obscured through liberal conceptualizations of violence. I focus on cases of interracial stranger attacks of Asian women and girls by men. I contend that these cases – that range from homicide, sexual assault, prowl by night, to tampering with a food product – are connected and are local manifestations of national and global power relations. I end by foregrounding how some of the non-Asian men targeting Asian women are men of colour. I argue that this violence is an assertion of the right to place and space in both national and global hierarchies informed by the neoliberal uplift of elite Asian men and capital, and western constructions of the Asia Pacific century. In highlighting the specificities of Asian gendered difference, the intent is less to include Asian women in theorizing on violence, and more to examine how an intersectional, relational, historically specific and structural analysis of gendered violence brings into clearer view the systems of domination that violence secures.
Trajectories of Maltreatment Re-Reports From Ages 4 to 12:
Authors: Proctor Laura J. , Aarons Gregory A. , Dubowitz Howard , English Diana J. , Lewis Terri , Thompson Richard , Hussey Jon M. , Litrownik Alan J. , Roesch Scott C.
Published: June 2012

This study identified trajectories of maltreatment re-reports between ages 4 and 12 for children first referred to Child Protective Services (CPS) for maltreatment prior to age 4 and either removed from the home or assessed by a CPS intake worker as moderately or highly likely to be abused/neglected in the future, absent intervention. Participants ( n = 501) were children from the Southwest and Northwest sites of the Consortium for Longitudinal Studies of Child Abuse and Neglect (LONGSCAN). During the 8-year follow-up period, 67% of children were re-reported. Growth mixture modeling identified four trajectory classes: No re-report (33%), Continuous re-reports (10%), Intermittent re-reports (37%), and Early re-reports (20%). Membership in classes with relatively more re-reports was predicted by several factors assessed at age 4, including physical abuse; living with a biological/stepparent; caregiver alcohol abuse, depression, and lack of social support; receipt of Aid to Families with Dependent Children (AFDC); and number of children in the home. For a subpopulation of high-risk children first reported in early childhood, risk for maltreatment re-reporting may persist longer than previously documented, continuing 8 to 12 years after the first report.
“Ex-Imprisoned Homicide Offenders: Once Bitten, Twice Shy?” The Effect of the Length of Imprisonment on Recidivism for Homicide Offenders
Authors: Baay Pieter , Liem Marieke , Nieuwbeerta Paul
Published: June 2012

This study aims to examine recidivism patterns and the influence of imprisonment length for all homicide offenders who have been convicted in the Netherlands between 1996 and 2004. In addition, we tested whether imprisonment effects differed between homicide offenders with different characteristics. Analyses on 621 homicide offenders indicate that longer imprisonment systematically increases recidivism frequency, not recidivism speed. We find some indications that imprisonment length increases recidivism to a greater extent for offenders with an intimate partner, with a Western ethnic background and for offenders with a relatively shorter detention history prior to the homicide.
Effects of Phthalates on the Human Corneal Endothelial Cell Line B4G12
Authors: Krüger Tanja , Cao Yi , Kjærgaard Søren K. , Knudsen Lisbeth E. , Bonefeld-Jørgensen Eva C.
Published: June 2012

Phthalates are industrial chemicals used in many cosmetics. We evaluated an in vitro model for eye irritancy testing using the human corneal endothelial cell line B4G12. Cell proliferation and toxicity were assessed after exposing to di- n-butyl phthalate (DBP), benzyl butyl phthalate (BBP), di-2-ethylhexyl phthalate (DEHP), diisodecyl phthalate (DIDP), di- n-octyl phthalate (DnOP), and di-isononyl phthalate (DINP). Gene expression and secretion of inflammatory cytokines were evaluated after exposure to DBP. Decreased cell proliferation was observed for the phthalates DBP, BBP, and DEHP, and cell toxicity was observed for DBP and BBP. Upon DBP exposure at nontoxic concentrations, a significant increased gene expression and cytokine cell secretion were observed for interleukin-1β (IL-1β) and IL-8, and also an increased IL-6 secretion was observed. In conclusion, the human corneal endothelial cell line B4G12 may be a potential model for inflammatory eye irritancy testing of phthalates.
The role of mitochondria in axonal degeneration and tissue repair in MS
Authors: van Horssen J , Witte ME , Ciccarelli O
Published: June 2012

Axonal injury is a key feature of multiple sclerosis (MS) pathology and is currently seen as the main correlate for permanent clinical disability. Although little is known about the pathogenetic mechanisms that drive axonal damage and loss, there is accumulating evidence highlighting the central role of mitochondrial dysfunction in axonal degeneration and associated neurodegeneration. The aim of this topical review is to provide a concise overview on the involvement of mitochondrial dysfunction in axonal damage and destruction in MS. Hereto, we will discuss putative pathological mechanisms leading to mitochondrial dysfunction and recent imaging studies performed in vivo in patients with MS. Moreover, we will focus on molecular mechanisms and novel imaging studies that address the role of mitochondrial metabolism in tissue repair. Finally, we will briefly review therapeutic strategies aimed at improving mitochondrial metabolism and function under neuroinflammatory conditions.
“I want the one that will heal me completely so it won’t come back again”: The limits of antipsychotic medication in rural Ghana
Authors: Read Ursula
Published: June 2012

Campaigns to scale up mental health services in low-income countries emphasise the need to improve access to psychotropic medication as part of effective treatment yet there is little acknowledgement of the limitations of psychotropic drugs as perceived by those who use them. This paper considers responses to treatment with antipsychotics by people with mental illness and their families in rural Ghana, drawing on an anthropological study of family experiences and help seeking for mental illness. Despite a perception among health workers that there was little popular awareness of biomedical treatment for mental disorders, psychiatric services had been used by almost all informants. However, in many cases antipsychotic treatment had been discontinued, even where it had been recognised to have beneficial effects such as controlling aggression or inducing sleep. Unpleasant side effects such as feelings of weakness and prolonged drowsiness conflicted with notions of health as strength and were seen to reduce the ability to work. The reduction of perceptual experiences such as visions was less valued than a return to social functioning. The failure of antipsychotics to achieve a permanent cure also cast doubt on their efficacy and strengthened suspicions of a spiritual illness which would resist medical treatment. These findings suggest that efforts to improve the treatment of mental disorders in low-income countries should take into account the limitations of antipsychotic drugs for those who use them and consider how local resources and concepts of recovery can be used to maximise treatment and support families.
The discovery of autism: Indian parents’ experiences of caring for their child with an autism spectrum disorder
Authors: Desai Miraj U. , Divan Gauri , Wertz Frederick J. , Patel Vikram
Published: June 2012

The current study investigated the lived experience of 12 parents of children with an Autism Spectrum Disorder in everyday cultural contexts in Goa, India. Narratives from parents collected between 2009 and 2010 were analyzed using the procedures of phenomenological psychology. Four temporal phases of parents’ experience emerged from these data. Findings showed that the earliest phase of the child’s life was a period of relative normalcy and social cohesion. In the second phase, the child’s behaviors began to disrupt the everyday social order, but parents viewed these unexpected behaviors as temporary. In the third phase, parents’ observations in public situations, along with assessments of others, led to a qualitative shift in which parents began to perceive that there was a persisting problem interfering with their child’s social and practical activities. In the fourth phase, parents grappled with developing their child’s capacities to meet existing practical opportunities in the local society, while attempting to reshape the social world to accommodate the abilities and limits of children like their own. Parents’ fundamental concerns throughout their journey were: learning to meet new and unfamiliar challenges as parents, caring for their child’s basic needs, and finding an engaging niche with a sense of belonging for their child in the everyday milieu. Both culture-specific and potentially universal levels of experience are delineated in the overall findings. Implications for culturally sensitive research and practice in India and other low- and middle-income countries are discussed.
The Role of Skill Versus Luck in Poker Evidence From the World Series of Poker
Authors: Levitt Steven D. , Miles Thomas J.
Published: June 2012

In determining the legality of online poker—a multibillion dollar industry—courts have relied heavily on the issue of whether or not poker is a game of skill. Using newly available data, the authors analyze that question by examining the performance in the 2010 World Series of Poker of a group of poker players identified as being highly skilled prior to the start of the events. Those players identified a priori as being highly skilled achieved an average return on investment of over 30%, compared to a −15% for all other players. This large gap in returns is strong evidence in support of the idea that poker is a game of skill.
Virtual Reality Simulator
Authors: Clarke David B. , D’Arcy Ryan C.N. , Delorme Sebastien , Laroche Denis , Godin Guy , Hajra Sujoy Ghosh , Brooks Rupert , DiRaddo Robert
Published: June 2012

Background. The overriding importance of patient safety, the complexity of surgical techniques, and the challenges associated with teaching surgical trainees in the operating room are all factors driving the need for innovative surgical simulation technologies. Technical development. Despite these issues, widespread use of virtual reality simulation technology in surgery has not been fully implemented, largely because of the technical complexities in developing clinically relevant and useful models. This article describes the successful use of the NeuroTouch neurosurgical simulator in the resection of a left frontal meningioma. Conclusion. The widespread application of surgical simulation technology has the potential to decrease surgical risk, improve operating room efficiency, and fundamentally change surgical training.
Sonic hedgehog pathway expression in non-small cell lung cancer
Authors: Savani Malvi , Guo Yan , Carbone David P. , Csiki Ildiko
Published: June 2012

Objective:

Activation of the hedgehog pathway is an important signaling mechanism crucial in embryogenesis and has strong links to carcinogenesis. This study investigates the expression of the Sonic hedgehog pathway molecules in non-small cell lung tumors as it relates to clinical outcome of various non-small cell lung cancers.

Methods:

A tissue microarray with 81 samples from 42 patients with various non-small cell lung cancer histologies was examined without the aid of laser microdissection. All samples were stained with antibodies directed against Sonic hedgehog, Ptch-1, Smoothened, and Gli-1.

Results:

Most of the tumor samples showed negative to weak expression of the pathway proteins (Sonic hedgehog, 38% negative to 20% weak; Ptch-1, 100% negative; Smoothened, 69% negative to 7% weak; Gli-1, 57% negative to 5% weak) compared with higher expression in normal lung epithelial cells.

Conclusion:

The same pathway expression did not correlate with clinical outcome. While our results do not provide any indication that the pathway molecules are correlated to overall patient survival possibly due to the limited sample size, our study shows minimum overexpression of Sonic hedgehog pathway in non-small cell lung cancer and this did not correlate clinically with patient outcome.
The role of biologic agents in damage progression in rheumatoid arthritis: indirect comparison of data coming from randomized clinical trials
Authors: Favalli Ennio Giulio , Pregnolato Francesca , Biggioggero Martina , Meroni Pier Luigi
Published: June 2012

Objectives:

All biologic agents approved for the treatment of rheumatoid arthritis (RA) have been tested versus methotrexate (MTX) for efficacy on damage progression in several randomized clinical trials (RCTs), but direct head-to-head comparisons have never been conducted. The purpose of this investigation is to analyse data coming from main RA RCTs and to perform an indirect comparison.

Methods:

A systematic review of literature from 1988 to 2011 was conducted. Only randomized, double-blind, controlled, comparative trials, with evaluation of radiographic progression were included. The radiographic score was standardized and mean difference in the percentage of the annual radiographic progression rate was used as the effect measure. Heterogeneity between studies was estimated by I2 test. For each trial, the effect was plotted according to its standard error in a funnel plot.

Results:

Of 44 potentially relevant trials, 12 RCTs were included in the study. In order to optimize RCTs comparison, studies were stratified in early and late RA group. Main population characteristics were similar in both early and late RA groups, whereas the standardized baseline radiographic score value significantly differs among trials in both early (range 2.7–21.9) and late (range 23.46–75) RA groups. The standardized annual estimated progression is similar across the late RA group. Strong evidence of heterogeneity ( I2 = 97%, p = 0.00001) but no asymmetry of the funnel plot was observed in the early RA group. Total mean difference was −16.28 (95% confidence interval [CI] −24.42 to −8.14). For the late RA group a random model was used ( I2 = 99%, p = 0.00001) and a total mean difference of −39.25 (95% CI −53.77 to −24.73) was found.

Conclusions:

All biologic agents provide a favourable effect on disease progression both in early and late RA. The significant heterogeneity among various RCTs did not allow an effective comparison of the performance of biologic agents in each study.
Assessing Predictive Power of Psychosocial Factors on Breastfeeding Behavior of Mothers Attending Postnatal Clinics in Western Kenya
Authors: Mutuli Lucy Amanya , Walingo Mary Khakoni , Othuon Lucas Ayado
Published: June 2012

This cross-sectional study aimed at determining predictive power of psychosocial factors influencing breastfeeding behavior of breastfeeding mothers. The study was conducted from April to August 2010 in Kakamega Central District within 4 postnatal clinics that were purposively sampled. Proportionate stratified technique was employed to obtain 230 respondents. A structured questionnaire was used to collect quantitative data where exploratory factor analysis tested dimensionality of questions, whereas skewness and kurtosis assessed normality of data. Structural equation modeling determined predictive power of latent variables. The model fitted data acceptably well, χ2 = 156, P < .001, Tucker–Lewis index = .93, comparative fit index = .95, root mean square error of approximation = .090, Hoelter’s critical N (0.01 = 230), with regard to breastfeeding behavior. Regression weights showed predictive power for maternal attitude (β = .38, P < .01), subjective norm (β = .25, P < .05), perceived behavioral control (β = .25, P < .05), and intention (β = .95, P < .001). This study provides information on a better approach for promoting optimal breastfeeding that will increase initiation, exclusivity, and breastfeeding continuation rates.
Moving Forward
Authors: Mazyck Donna
Published: June 2012

NASN’s new Executive Director shares reflections on NASN’s past and present with an emphasis on the future.
Horses, guns and governments: A comparative study of the military transition in the Manchu, Mughal, Ottoman and Safavid empires, circa 1400 to circa 1750
Authors: Roy Kaushik
Published: June 2012

The experts of Western European warfare agree that Western Europe during the early modern era (i.e. the period roughly from 1500 to 1750) experienced substantial military changes. One of the crucial components of the early modern Western European military transition was the spread and development of gunpowder weapons in both land and sea warfare. Scholars disagree on the impact of the Western European military transition on the extra-European world. A comparative study of the military systems of the big Asian empires’ military system would throw light on this thorny issue, and this is the objective of the present work. This essay attempts a comparative analysis of the armies and navies of the large agrarian bureaucratic empires of Asia (Ottoman, Safavid, Manchus/Qing and the Mughals), which were major powers in terms of political, military and economic strength before the onset of industrialization around 1800. This study will focus on the question of how far the Asian polities were able to integrate gunpowder weapons into their military systems.
Human regulatory T cells induce T-lymphocyte senescence
Authors: Ye Jian , Huang Xingxu , Hsueh Eddy C. , Zhang Qunyuan , Ma Chunling , Zhang Yanping , Varvares Mark A. , Hoft Daniel F. , Peng Guangyong
Published: June 2012

Regulatory T (Treg) cells have broad suppressive activity on host immunity, but the fate and function of suppressed responder T cells remains largely unknown. In the present study, we report that human Treg cells can induce senescence in responder naive and effector T cells in vitro and in vivo. Senescent responder T cells induced by human Treg cells changed their phenotypes and cytokine profiles and had potent suppressive function. Furthermore, Treg-mediated molecular control of senescence in responder T cells was associated with selective modulation of p38 and ERK1/2 signaling and cell-cycle–regulatory molecules p16, p21, and p53. We further revealed that human Treg-induced senescence and suppressor function could be blocked by TLR8 signaling and/or by specific ERK1/2 and p38 inhibition in vitro and in vivo in animal models. The results of the present study identify a novel mechanism of human Treg cell suppression that induces targeted responder T-cell senescence and provide new insights relevant for the development of strategies capable of preventing and/or reversing Treg-induced immune suppression.