bluuebunny/crossref_metadata_2025 huggingface dataset:
A Comparison of Exposure Control Procedures in CATs Using the 3PL Model
Authors: Leroux Audrey J. , Lopez Myriam , Hembry Ian , Dodd Barbara G.
Published: April 2013

This study compares the progressive-restricted standard error (PR-SE) exposure control procedure to three commonly used procedures in computerized adaptive testing, the randomesque, Sympson–Hetter (SH), and no exposure control methods. The performance of these four procedures is evaluated using the three-parameter logistic model under the manipulated conditions of item pool size (small vs. large) and stopping rules (fixed-length vs. variable-length). PR-SE provides the advantage of similar constraints to SH, without the need for a preceding simulation study to execute it. Overall for the large and small item banks, the PR-SE method administered almost all of the items from the item pool, whereas the other procedures administered about 52% or less of the large item bank and 80% or less of the small item bank. The PR-SE yielded the smallest amount of item overlap between tests across conditions and administered fewer items on average than SH. PR-SE obtained these results with similar, and acceptable, measurement precision compared to the other exposure control procedures while vastly improving on item pool usage.
Alfonso Guida: Un fedele della poesia
Authors: Falotico Caterina
Published: April 2013

La produzione di Alfonso Guida, rivelazione della poesia italiana di questi anni, viene esplorata nelle sue due prime raccolte. Nel Dono dell’occhio la sofferenza psichica, da cui il poeta è assediato, si materializza in Torremozza con unico scampo nella natura e nella storia della Lucania magno-greca. In Irpinia il sisma devastante del 1980 consente di oggettivare la frantumazione interiore in un afflato di solidarietà con le vittime vicine e lontane. Dal lirismo alla coralità tragica.
Another View on the Relationship Between Democratization and Intra-Military Division in South Korea
Authors: Heo Uk , Yun Seongyi
Published: April 2013

Armed Forces and Society recently published an article, “Intra-Military Division and Democratization in South Korea” by Insoo Kim. In the article, Kim argues that economic development and civil society explanations for South Korea’s democratization are not sufficient because conflict in the military undermined the ability of Chun’s government to suppress the democracy movement, which made the transition possible. We refute Kim’s argument because economic development clearly made significant contribution to South Korea’s democratization by enhancing education attainment and facilitating industrialization and urbanization. Moreover, there is no clear evidence of schism in the military or among political elites, and the authoritarian leader Chun Doo-hwan agreed to change the presidential election system based on his political calculation.
Testing Psychometric Properties of the 30-Item General Health Questionnaire
Authors: Klainin-Yobas Piyanee , He Hong-Gu
Published: April 2013

This study aimed to evaluate the psychometric properties of the General Health Questionnaire (GHQ-30) given conflicting findings in the literature. A cross-sectional, nonexperimental research was used with a convenience sample of 271 American female health care professionals. Data were collected by using self-reported questionnaires. A series of exploratory factor analyses (EFAs), confirmatory factor analyses (CFAs), and structural equation modeling (SEM) were performed to examine underlying dimensions of the GHQ-30.Results from EFAs and CFAs revealed the three-factor composition (positive affect, anxiety, and depressed mood). All factor loadings were statistically significant, and one pair of error variance was allowed to be correlated. All factors contained questionnaire items with acceptable face validity and demonstrated good internal consistency reliability. Results from SEM further confirmed underlying constructs of the scale. To our knowledge, this is the first study that extensively tested the psychometric properties of the GHQ-30, taking both statistical and substantive issues into consideration.
Are any biocompatible coatings capable of attenuating the deleterious effects of cardiopulmonary bypass?
Authors: Marcoux JE , Mycyk TR
Published: April 2013

Background:

Biocompatible circuits (BCC) are intended to decrease the activation of blood to the artificial cardiopulmonary bypass (CPB) surface. Typically, the coatings are made of various inert substances or molecules physiologically similar to endothelium. Thromboelastography (TEG) graphically represents clot formation, strength of clotting and fibrinolysis. TEG analysis was undertaken to determine if coagulation could be preserved by the BCC.

Methods:

Five different BCC were studied in clinical applications. These five coated circuits were then compared to an identical circuit where only the oxygenator was coated. A pre- and post-bypass TEG was done for comparison. Six well-studied parameters of TEG analysis were compared: R time, Angle, K, Maximum Amplitude (MA), LY30% and Clot Index (CI). Postoperative bleeding and transfusion requirements were compared to TEG results for comparison.

Results:

All postoperative TEG results were significantly different from preoperative parameters except LY30%. No BCC circuit was able to prevent the significant disruption of the observed TEG coagulation parameters R, K, angle, MA and CI. Of note, the postoperative TEG parameters resulting from the Control and Trillium™ groups – which had the same type of oxygenator – were practically identical. The oxygenator, which represents the largest surface area in the CPB circuit, is the single most important factor influencing coagulation.

Conclusion:

While not harmful, BCC are ineffective in preserving TEG coagulation parameters post CPB. Clinical findings support laboratory TEG results in that there were no differences in bleeding or transfusion requirements between groups.
The use of extracorporeal membrane oxygenation in pediatric patients with sickle cell disease
Authors: Kuo KW , Cornell TT , Shanley TP , Odetola FO , Annich GM
Published: April 2013

Previous reports have described the use of extracorporeal membrane oxygenation (ECMO) for acute chest syndrome of sickle cell disease (SCD). However, there have been no reports of venoarterial (VA) ECMO for cardiac dysfunction in patients with SCD. We describe a patient with SCD and life-threatening cardiogenic shock who was successfully treated with VA ECMO. Furthermore, SCD patients have unique comorbidities that warrant particular consideration when utilizing ECMO. We discuss these considerations and review the documented experience with ECMO for pediatric SCD patients from the Extracorporeal Life Support Organization (ELSO) registry. From 1990 until 2012, 52% of the 65 pediatric patients with SCD placed on ECMO survived, with 85% of those receiving venovenous (VV) ECMO surviving and 43% of those receiving VA ECMO surviving. However, significant complications, such as bleeding, neurological injury and kidney injury, also occurred with both VV and VA ECMO. Ten percent of SCD patients receiving VA ECMO experienced either a cerebral infarct or hemorrhage; our patient suffered a cerebrovascular accident while on ECMO, though she survived with good neurologic outcome. To our knowledge, this is the first report of a pediatric patient with SCD and cardiogenic shock successfully managed with VA ECMO. In conjunction with the ELSO registry review, this case report suggests that, while VA ECMO can be successfully used in patients with SCD and severe cardiovascular dysfunction, clinicians should also be aware of the potential for serious complications in this high-risk population.
A question prompt list for patients with advanced cancer in the final year of life: Development and cross-cultural evaluation
Authors: Walczak Adam , Mazer Benjamin , Butow Phyllis N , Tattersall Martin HN , Clayton Josephine M , Davidson Patricia M , Young Jane , Ladwig Susan , Epstein Ronald M
Published: April 2013

Background:

Clinicians and patients find prognosis and end-of-life care discussions challenging. Misunderstanding one’s prognosis can contribute to poor decision-making and end-of-life quality of life. A question prompt list (booklet of questions patients can ask clinicians) targeting these issues may help overcome communication barriers. None exists for end-of-life discussions outside the palliative care setting.

Aim:

To develop/pilot a question prompt list facilitating discussion/planning of end-of-life care for oncology patients with advanced cancer from Australia and the United States and to explore acceptability, perceived benefits/challenges of using the question prompt list, suggestions for improvements and the necessity of country-specific adaptations.

Design:

An expert panel developed a question prompt list targeting prognosis and end-of-life issues. Australian/US semi-structured interviews and one focus group elicited feedback about the question prompt list. Transcribed data were analysed using qualitative methods.

Setting/participants:

Thirty-four patients with advanced cancer (15 Australian/19 US) and 13 health professionals treating such patients (7 Australian/6 US) from two Australian and one US cancer centre participated.

Results:

Most endorsed the entire question prompt list, though a minority queried the utility/appropriateness of some questions. Analysis identified four global themes: (1) reinforcement of known benefits of question prompt lists, (2) appraisal of content and suggestions for further developments, (3) perceived benefits and challenges in using the question prompt list and (4) contrasts in Australian/US feedback. These contrasts necessitated distinct Australian/US final versions of the question prompt list.

Conclusions:

Participants endorsed the question prompt list as acceptable and useful. Feedback resulted in two distinct versions of the question prompt list, accommodating differences between Australian and US approaches to end-of-life discussions, highlighting the appropriateness of tailoring communication aides to individual populations.
Impact of a palliative care initiative on end-of-life care in the general wards: A before-and-after study
Authors: Tan Adeline , Seah Angeline , Chua Gerald , Lim Tow Keang , Phua Jason
Published: April 2013

Background:

Data on deaths in the general wards of our hospital in 2007 revealed infrequent discussions on end-of-life care and excessive burdensome interventions.

Aim:

A physician order form to withhold inappropriate life-sustaining interventions was initiated in 2009. The use of the form was facilitated by staff educational sessions and a palliative care consult service. This study aims to evaluate the impact of these interventions in 2010.

Design:

Retrospective medical chart review with comparisons was made for the following: baseline patient characteristics, orders concerning life-sustaining therapies, treatment provided in last 24 h of life, and discussion of specific life-sustaining therapies with patients and families.

Settings/participants:

This study included all adult patients who died in our hospital’s general wards in 2007 ( N = 683) versus 2010 ( N = 714).

Results:

There was an increase in orders to withhold life-sustaining therapies, such as cardiopulmonary resuscitation (66.2%–80.0%). There was a decrease in burdensome interventions such as antibiotics (44.9%–24.9%) and a small increase in palliative treatments such as analgesia (29.1%–36.7%). There were more discussions on the role of cardiopulmonary resuscitation with conversant patients (4.6%–10.2%) and families (56.5%–79.8%) ( p-value all < 0.05). On multivariate analysis, the physician order form independently predicted orders to withhold cardiopulmonary resuscitation.

Conclusions:

A multifaceted intervention of a physician order form, educational sessions, and palliative care consult service led to an improvement in documentation of end-of-life discussions and was associated with an increase in such discussions and less burdensome treatments. There were small improvements in the proportion of palliative treatments administered.
US Valuation of the SF-6D
Authors: Craig Benjamin M. , Pickard A. Simon , Stolk Elly , Brazier John E.
Published: April 2013

Background. The original SF-6D valuation study collected 3503 standard gambled responses from 611 UK respondents to predict quality-adjusted life year (QALY) values. Methods. Using 19,980 paired comparison responses from 666 US respondents and a stacked probit model, the 25 coefficients of the original SF-6D multiattribute utility (MAU) regression were estimated, such that each coefficient represents a QALY decrement. The US QALY predictions were compared with UK predictions using 8428 SF-6D states in the US Medicare Health Outcomes Survey (MHOS), 1998 to 2003. Results. Twenty-two of the 25 decrements in the SF-6D MAU regression are statistically significant. The remaining decrements are insignificant based on US and UK results. The US and UK QALY predictions for the MHOS SF-6D states are remarkably similar given differences in experimental design, format, and sampling (Lin’s coefficient of agreement, 0.941; absolute mean difference, 0.043). Limitations. The underlying theoretical framework for the study design and econometric analysis builds from the episodic random utility model and the concept of QALYs and inherits their limitations. Conclusions. This study enhances the potential for US comparative effectiveness research by translating SF-6D states into US QALYs as well as improves upon discrete choice experiment design and econometric methods for health valuation.
The Challenge of Assessing Creative Problem Solving in Client-Based Marketing Development Projects
Authors: Jaskari Minna-Maarit
Published: April 2013

Creativity and marketing imagination are essential core competencies for marketers. Therefore, higher marketing education emphasizes creativity in several ways. However, assessing creativity and creative problem solving is challenging and tools for this purpose have not been developed in the context of marketing education. To address this gap, we analyze the use of Structure of the Observed Learning Outcome (SOLO) taxonomy as an assessment tool in creative problem solving and in doing so develop an assessment framework by contextualizing SOLO taxonomy for client-based marketing development projects. We first introduce earlier literature on assessment and SOLO taxonomy. We then describe a client-based marketing course on creative problem solving. We use SOLO taxonomy to analyze the outcomes and development processes of six student projects and in doing so develop an assessment framework for creative problem solving. Finally, we give suggestions for teachers on how to enhance creative problem solving and its assessment in marketing classrooms.
Zoster-associated segmental paresis in a patient with cervical spinal stenosis
Authors: Kang Sung-Hee , Song Ho-Kyung , Jang Yeon
Published: April 2013

Segmental zoster paresis is a rare complication of herpes zoster, characterized by focal motor weakness that does not always present simultaneously with skin lesions. Zoster paresis can be easily confused with other neuromuscular or spinal diseases. This case report describes the case of a 72-year-old woman with herpes zoster and cervical spinal stenosis at the same spinal level, where it was difficult to distinguish segmental zoster paresis from cervical radiculopathy combined with motor neuropathy. Although segmental zoster paresis in the upper extremity is rare, it should be included in the differential diagnosis of segmental pain and weakness in the extremities, especially in older or immunocompromised patients. Correct diagnosis is required, to avoid unnecessary surgery and allow timely antiviral treatment.
Central and eastern European industrial relations in the crisis: national divergence and path-dependent change
Authors: Glassner Vera
Published: April 2013

This article assesses the effects of the recent economic crisis on industrial relations in the central and eastern European EU Member States. The analysis is based on the theoretical framework of three types of central and eastern European capitalism: neoliberal, embedded neoliberal and neocorporatist (Bohle and Greskovits, 2012). The article introduces the individual articles of this issue, arguing that the impact of the crisis on collective bargaining processes and institutions is shaped by economic and political factors and, above all, by the institutional setting of industrial relations. Trade union responses are explained by the varying use of two strategic sources of power: participation in formal collective bargaining (institutional power) and a strengthening of the membership base (membership power). Despite considerable differences between countries with regard to these factors, recent developments in collective bargaining have tended to be path-dependent and have resulted in a further shift of the region’s industrial relations towards neoliberalism.
ADHD and Hyperkinetic Disorder Symptoms in Australian Adults
Authors: Gomez Rapson
Published: April 2013

Objective: ADHD and Hyperkinetic Disorder (HKD) have the same 18 symptoms, covering inattention (IA), hyperactivity (HYP), and impulsivity (IMP). This study was aimed at providing descriptive scores for the different symptom groups in these disorders and how these scores varied by age and gender, the percentages of individuals meeting the symptom thresholds for the different ADHD types and HKD, the factor structure, and gender invariance of these symptoms in adults. Method: To accomplish this, 852 adults provided self-ratings for a scale comprising the 18 ADHD/HKD symptoms. Results: The findings showed that age and gender had minimal effects on the ADHD symptoms. Also, in terms of symptom counts, 2% had HKD and 6.3% had ADHD (inattentive = 1.6%, hyperactive-impulsive = 2.7%, and combined type = 2.0%). Confirmatory factor analysis (CFA) provided most support for the three-factor HKD model, involving separate factors for the IA, HYP, and IMP symptoms. This model showed full measurement invariance across gender. Conclusion: The theoretical and clinical implications of the findings are discussed.
Effects of angiotensin II blockade on cardiomyocyte regeneration after myocardial infarction in rats
Authors: Segersvärd Heli , Lakkisto Päivi , Forsten Hanna , Immonen Katariina , Kosonen Riikka , Palojoki Eeva , Kankuri Esko , Harjula Ari , Laine Mika , Tikkanen Ilkka
Published: April 2013

Introduction:

We studied the effects of angiotensin type 1 receptor blockade (ARB) on formation of new cardiomyocytes, neovascularization and ventricular remodelling after myocardial infarction (MI).

Methods:

Male Wistar rats with MI or sham-operated controls were treated with either losartan or vehicle. Bromodeoxyuridine (BrdU) was given to identify newly formed cardiac cells. Immunohistochemical analysis was used to quantify proliferative and apoptotic cardiomyocytes, vascular structures and c-Kit+ stem/progenitor cells, western blotting to evaluate gene expression, and planimetry and echocardiography to assess cardiac structure and function.

Results:

The number of BrdU+ cardiomyocytes increased similarly in the vehicle and losartan treated MI groups. The number of apoptotic or proliferating cardiomyocytes did not differ between losartan and vehicle treated rats. Losartan induced an increase in capillary and BrdU+ vascular densities in the infarct border zone. Losartan treatment completely prevented post-MI cardiac hypertrophy. In the non-infarcted myocardium the amount of all BrdU+ cells (including non-cardiomyocyte cells) was highest in the vehicle treated MI rats at week 4.

Conclusions:

The number of newly formed cardiomyocytes increased after MI. Angiotensin II blockade neither stimulated nor prevented cardiomyocyte regeneration. ARB treatment increased vascular densities in the infarct border zone and modulated remodelling of the non-infarcted myocardium preventing effectively post-MI cardiac hypertrophy.
Mood Effects of Televised Sports Events
Authors: Knoll Johannes , Schramm Holger , Schallhorn Christiana
Published: April 2013

Television viewers attend to sports programs primarily to gain emotional rewards. As not only wins but also defeats are inherently rooted in sport competitions, television viewers can be positively as well as negatively affected in their feelings when watching sports on television. Interestingly, some studies were able to show that the feelings evoked by watching sport television also influence viewers’ judgments, following feeling-as-information theory. The present study builds on these results by investigating the mood effect of viewing televised football Fédération Internationale de Football Association World Cup games on personal as well as economic estimations of viewers. A quasi-experimental design was employed, assessing the moods and estimations of viewers before and after a win and a defeat of the German national team. The results support feeling-as-information theory, as viewers reported enhanced mood and estimations after watching the victory. Results of previous studies are extended, as longer term effects are included and the mediating role of mood was explicitly tested and supported.
Human marrow stromal cells reduce microglial activation to protect motor neurons in a transgenic mouse model of amyotrophic lateral sclerosis
Authors: Zhou Chang , Zhang Chen , Zhao Renliang , Chi Song , Ge Ping , Zhang Cheng
Published: April 2013

Background

Human marrow stromal cells (hMSCs) injected intrathecally can effectively increase the lifespan and protect motor neurons in a transgenic mouse model of amyotrophic lateral sclerosis. However, how the transplanted cells exert a neuroprotective effect is still unclear. More recently, the anti-inflammation effect of marrow stromal cells has generated a great deal of interest. In the present study, we sought to investigate whether intrathecally injected hMSCs protect motor neurons through attenuating microglial activation and the secretion of inflammatory factors in Cu/Zn superoxide dismutase 1 (SOD1) transgenic mice. In addition, we also focused on the mode of hMSCs inhibiting microglial activation.

Methods

We transplanted hMSCs into the cisterna magna of SOD1 mice at the age of 8, 10 and 12 weeks. At sacrifice, tissues were harvested for analysis of neuron counts, microglial activation, TNFα secretion and inducible nitric oxide synthase (iNOS) protein expression. In vitro, microglial cells were treated with hMSC co-culture, hMSC transwell culture or hMSC conditioned medium to investigate the mode of hMSCs exerting an anti-inflammation effect.

Results

Intrathecally transplanted hMSCs inhibited inflammatory response in SOD1 transgenic mice, which was evidenced by the decreases in microglial activation, TNFα secretion and iNOS protein expression. In addition, the inhibitory effect on microglial activation of hMSCs was through secretion of diffusible molecules adjusted to environmental cues.

Conclusion

Intrathecally injected hMSCs can attenuate microglial activation through secretion of diffusible molecules to exert a therapeutic effect in SOD1 transgenic mice. Further studies are needed to explore the exact mechanisms by which hMSCs inhibit inflammation for facilitating the therapeutic effect.
Metabolic engineering of Escherichia colifor the biosynthesis of alpha-pinene
Authors: Yang Jianming , Nie Qingjuan , Ren Meng , Feng Hongru , Jiang Xinglin , Zheng Yanning , Liu Min , Zhang Haibo , Xian Mo
Published: April 2013

Background

α-Pinene is an important natural product that is widely used in flavorings, fragrances, medicines, fine chemicals and high-density renewable fuels. Currently, α-Pinene used in industry is mainly produced either by tapping trees (gum turpentine) or as a byproduct of paper pulping (crude sulfate turpentine, CST). However, the extraction of it from trees is tedious and inefficient and requires substantial expenditure of natural resources. Therefore, it is necessary to seek sustainable technologies for α-pinene production.

Results

To construct the microbial synthetic pathway of α-pinene in E. coli, we co-expressed native geranyl diphosphate synthase (IspA) from E. coli and α-pinene synthase (Pt30) from Pinus taeda, and then to increase the geranyl diphosphate (GPP) content in the cells, a suitable geranyl diphosphate synthase (GPPS2) was selected from two different origins. Furthermore, to enhance α-pinene production, a novel biosynthetic pathway of α-pinene was assembled in E. coli BL21(DE3) with the heterologous hybrid mevalonate (MVA) pathway, GPPS2 and α-pinene synthase (Pt30). The final genetic strain, YJM28, harboring the above novel biosynthetic pathway of α-pinene, accumulated α-pinene up to 5.44 mg/L and 0.97 g/L under flask and fed-batch fermentation conditions, respectively. The conversion efficiency of glucose to α-pinene (gram to gram) in the metabolically engineered strain reached 2.61%.

Conclusions

In this paper, by using metabolic engineering techniques, the more efficient biosynthetic pathway of α-pinene was successfully assembled in E. coli BL21(DE3) with the heterologous hybrid MVA pathway, GPPS2 and α-pinene synthase (Pt30). In addition, this is the first report on α-pinene fed-batch fermentation, and our results represent improvements over previous reports.
Cyclohexa-2,5-diene-1,4-dione-based antiproliferative agents: design, synthesis, and cytotoxic evaluation
Authors: Petronzi Carmen , Festa Michela , Peduto Antonella , Castellano Maria , Marinello Jessica , Massa Antonio , Capasso Anna , Capranico Giovanni , La Gatta Annalisa , De Rosa Mario , Caraglia Michele , Filosa Rosanna
Published: April 2013

Background

Tumors are diseases characterized by uncontrolled cell growth and, in spite of the progress of medicine over the years, continue to represent a major threat to the health, requiring new therapies. Several synthetic compounds, such as those derived from natural sources, have been identified as anticancer drugs; among these compounds quinone represent the second largest class of anticancer agents in use. Several studies have shown that these act on tumor cells through several mechanisms. An important objective of this work is to develop quinoidscompounds showing antitumor activity, but with fewer side effects. The parachinone cannabinol HU-331, is a small molecule that with its core 4-hydroxy-1,4-benzoquinone, exhibits a potent and selective cytotoxic activity on different tumor cell lines. A series of derivatives 3-hydroxy-1,4-benzochinoni were thus developed through HU-331 chemical modifications. The purpose of the work is to test the ability of the compounds to induce proliferative inhibition and study the mechanisms of cell death.

Methods

The antitumor activities were evaluated in vitro by examining their cytotoxic effects against different human cancer cell lines. All cell lines tested were plated in 96-multiwell and treated with HU-100-V at different concentrations and cell viability was evaluated byMTT assay. Subsequently via flow cytometry (FACS) it was possible to assess apoptosis by the system of double labeling with PI and Annexin-V, and the effect of the compounds on ROS formation by measuring the dichlorofluorescein fluorescence.

Results

The substitution by n-hexyl chain considerably enhanced the bioactivity of the compounds. In details, 2-hexyl-5-hydroxycyclohexa-2,5-diene-1,4-dione (V), 2,5-Dimethoxy-3-hexyl-2,5-cyclohexadiene-1,4-dione (XII) and 2-hydroxy-5-methoxy-3-hexyl-cyclohexa-2,5-diene-1,4-dione (XIII) showed most prominent cytotoxicity against almost human tumour cell lines. Compound V was further subjected to downstream apoptotic analysis, demostrating a time-dependent pro-apoptotic activity on human melanoma M14 cell line mediated by caspases activation and poly-(ADP-ribose)-polymerase (PARP) protein cleavage.

Conclusions

These findings indicate that 2-hexyl-5-idrossicicloesa-2,5-diene-1,4-dione can be a promising compound for the design of a new class of antineoplastic derivatives.

Carmen Petronzi, Michela Festa, Antonella Peduto and Maria Castellano: equally contributed equally to this work.
Pooled Analysis of the Prognostic and Predictive Effects of KRAS Mutation Status and KRAS Mutation Subtype in Early-Stage Resected Non–Small-Cell Lung Cancer in Four Trials of Adjuvant Chemotherapy
Authors: Shepherd Frances A. , Domerg Caroline , Hainaut Pierre , Jänne Pasi A. , Pignon Jean-Pierre , Graziano Stephen , Douillard Jean-Yves , Brambilla Elizabeth , Le Chevalier Thierry , Seymour Lesley , Bourredjem Abderrahmane , Teuff Gwénaël Le , Pirker Robert , Filipits Martin , Rosell Rafael , Kratzke Robert , Bandarchi Bizhan , Ma Xiaoli , Capelletti Marzia , Soria Jean-Charles , Tsao Ming-Sound
Published: April 2013

Purpose

We undertook this analysis of KRAS mutation in four trials of adjuvant chemotherapy (ACT) versus observation (OBS) to clarify the prognostic/predictive roles of KRAS in non–small-cell lung cancer (NSCLC).

Methods

KRAS mutation was determined in blinded fashion. Exploratory analyses were performed to characterize relationships between mutation status and subtype and survival outcomes using a multivariable Cox model.

Results

Among 1,543 patients (763 OBS, 780 ACT), 300 had KRAS mutations (codon 12, n = 275; codon 13, n = 24; codon 14, n = 1). In OBS patients, there was no prognostic difference for overall survival for codon-12 (mutation v wild type [WT] hazard ratio [HR] = 1.04; 95% CI, 0.77 to 1.40) or codon-13 (HR = 1.01; 95% CI, 0.47 to 2.17) mutations. No significant benefit from ACT was observed for WT-KRAS (ACT v OBS HR = 0.89; 95% CI, 0.76 to 1.04; P = .15) or codon-12 mutations (HR = 0.95; 95% CI, 0.67 to 1.35; P = .77); with codon-13 mutations, ACT was deleterious (HR = 5.78; 95% CI, 2.06 to 16.2; P < .001; interaction P = .002). There was no prognostic effect for specific codon-12 amino acid substitution. The effect of ACT was variable among patients with codon-12 mutations: G12A or G12R (HR = 0.66; P = .48), G12C or G12V (HR = 0.94; P = .77) and G12D or G12S (HR = 1.39; P = .48; comparison of four HRs, including WT, interaction P = .76). OBS patients with KRAS-mutated tumors were more likely to develop second primary cancers (HR = 2.76, 95% CI, 1.34 to 5.70; P = .005) but not ACT patients (HR = 0.66; 95% CI, 0.25 to 1.75; P = .40; interaction, P = .02).

Conclusion

KRAS mutation status is not significantly prognostic. The potential interaction in patients with codon-13 mutations requires validation. At this time, KRAS status cannot be recommended to select patients with NSCLC for ACT.
ProNGF promotes neurite growth from a subset of NGF-dependent neurons by a p75NTR-dependent mechanism
Authors: Howard Laura , Wyatt Sean , Nagappan Guhan , Davies Alun M.
Published: April 2013

The somatosensory and sympathetic innervation of the vertebrate head is derived principally from the neurons of trigeminal and superior cervical ganglia (SCG), respectively. During development, the survival of both populations of neurons and the terminal growth and branching of their axons in the tissues they innervate is regulated by the supply of nerve growth factor (NGF) produced by these tissues. NGF is derived by proteolytic cleavage of a large precursor protein, proNGF, which is recognised to possess distinctive biological functions. Here, we show that proNGF promotes profuse neurite growth and branching from cultured postnatal mouse SCG neurons. In marked contrast, proNGF does not promote the growth of trigeminal neurites. Studies using compartment cultures demonstrated that proNGF acts locally on SCG neurites to promote growth. The neurite growth-promoting effect of proNGF is not observed in SCG neurons cultured from p75NTR-deficient mice, and proNGF does not phosphorylate the NGF receptor tyrosine kinase TrkA. These findings suggest that proNGF selectively promotes the growth of neurites from a subset of NGF-responsive neurons by a p75NTR-dependent mechanism during postnatal development when the axons of these neurons are ramifying within their targets in vivo.
C. elegansGATA factors EGL-18 and ELT-6 function downstream of Wnt signaling to maintain the progenitor fate during larval asymmetric divisions of the seam cells
Authors: Gorrepati Lakshmi , Thompson Kenneth W. , Eisenmann David M.
Published: April 2013

The C. elegans seam cells are lateral epithelial cells arrayed in a single line from anterior to posterior that divide in an asymmetric, stem cell-like manner during larval development. These asymmetric divisions are regulated by Wnt signaling; in most divisions, the posterior daughter in which the Wnt pathway is activated maintains the progenitor seam fate, while the anterior daughter in which the Wnt pathway is not activated adopts a differentiated hypodermal fate. Using mRNA tagging and microarray analysis, we identified the functionally redundant GATA factor genes egl-18 and elt-6 as Wnt pathway targets in the larval seam cells. EGL-18 and ELT-6 have previously been shown to be required for initial seam cell specification in the embryo. We show that in larval seam cell asymmetric divisions, EGL-18 is expressed strongly in the posterior seam-fated daughter. egl-18 and elt-6 are necessary for larval seam cell specification, and for hypodermal to seam cell fate transformations induced by ectopic Wnt pathway overactivation. The TCF homolog POP-1 binds a site in the egl-18 promoter in vitro, and this site is necessary for robust seam cell expression in vivo. Finally, larval overexpression of EGL-18 is sufficient to drive expression of a seam marker in other hypodermal cells in wild-type animals, and in anterior hypodermal-fated daughters in a Wnt pathway-sensitized background. These data suggest that two GATA factors that are required for seam cell specification in the embryo independently of Wnt signaling are reused downstream of Wnt signaling to maintain the progenitor fate during stem cell-like divisions in larval development.
A comparison of proximal and distal chevron osteotomy for the correction of moderate hallux valgus deformity
Authors: Park C-H. , Jang J-H. , Lee S-H. , Lee W-C.
Published: April 2013

The purpose of this study was to compare the results of proximal and distal chevron osteotomy in patients with moderate hallux valgus.

We retrospectively reviewed 34 proximal chevron osteotomies without lateral release (PCO group) and 33 distal chevron osteotomies (DCO group) performed sequentially by a single surgeon. There were no differences between the groups with regard to age, length of follow-up, demographic or radiological parameters. The clinical results were assessed using the American Orthopaedic Foot and Ankle Society (AOFAS) scoring system and the radiological results were compared between the groups.

At a mean follow-up of 14.6 months (14 to 32) there were no significant differences in the mean AOFAS scores between the DCO and PCO groups (93.9 (82 to 100) and 91.8 (77 to 100), respectively; p = 0.176). The mean hallux valgus angle, intermetatarsal angle and sesamoid position were the same in both groups. The metatarsal declination angle decreased significantly in the PCO group (p = 0.005) and the mean shortening of the first metatarsal was significantly greater in the DCO group (p < 0.001).

We conclude that the clinical and radiological outcome after a DCO is comparable with that after a PCO; longer follow-up would be needed to assess the risk of avascular necrosis.

Cite this article: Bone Joint J 2013;95-B:649–56.
Intra-operative neurophysiological prediction of upper trunk recovery in obstetric brachial plexus palsy with neuroma in continuity
Authors: Chin K. F. , Misra V. P. , Sicuri G. M. , Fox M. , Sinisi M.
Published: April 2013

We investigated the predictive value of intra-operative neurophysiological investigations in obstetric brachial plexus injuries. Between January 2005 and June 2011 a total of 32 infants of 206 referred to our unit underwent exploration of the plexus, including neurolysis. The findings from intra-operative electromyography, sensory evoked potentials across the lesion and gross muscular response to stimulation were evaluated. A total of 22 infants underwent neurolysis alone and ten had microsurgical reconstruction. Of the former, one was lost to follow-up, one had glenoplasty and three had subsequent nerve reconstructions. Of the remaining 17 infants with neurolysis, 13 (76%) achieved a modified Mallet score > 13 at a mean age of 3.5 years (0.75 to 6.25). Subluxation or dislocation of the shoulder is a major confounding factor. The positive predictive value and sensitivity of the intra-operative EMG for C5 were 100% and 85.7%, respectively, in infants without concurrent shoulder pathology. The positive and negative predictive values, sensitivity and specificity of the three investigations combined were 77%, 100%, 100% and 57%, respectively.

In all, 20 infants underwent neurolysis alone for C6 and three had reconstruction. All of the former and one of the latter achieved biceps function of Raimondi grade 5. The positive and negative predictive values, sensitivity and specificity of electromyography for C6 were 65%, 71%, 87% and 42%, respectively.

Our method is effective in evaluating the prognosis of C5 lesion. Neurolysis is preferred for C6 lesions.

Cite this article: Bone Joint J 2013;95-B:699–705.
Revision of an unstable hemiarthroplasty or anatomical total shoulder replacement using a reverse design prosthesis
Authors: Abdel M. P. , Hattrup S. J. , Sperling J. W. , Cofield R. H. , Kreofsky C. R. , Sanchez-Sotelo J.
Published: April 2013

Instability after arthroplasty of the shoulder is difficult to correct surgically. Soft-tissue procedures and revision surgery using unconstrained anatomical components are associated with a high rate of failure. The purpose of this study was to determine the results of revision of an unstable anatomical shoulder arthroplasty to a reverse design prosthesis. Between 2004 and 2007, 33 unstable anatomical shoulder arthroplasties were revised to a reverse design. The mean age of the patients was 71 years (53 to 86) and their mean follow-up was 42 months (25 to 71). The mean time to revision was 26 months (4 to 164). Pain scores improved significantly (pre-operative visual analogue scale (VAS) of 7.2 (sd 1.6); most recent VAS 2.2 (sd 1.9); p = 0.001). There was a statistically significant increase in mean active forward elevation from 40.2° (sd 27.3) to 97.0° (sd 36.2) (p = 0.001). There was no significant difference in internal (p = 0.93) or external rotation (p = 0.40). Radiological findings included notching in five shoulders (15%) and heterotopic ossification of the inferior capsular region in three (9%). At the last follow-up 31 shoulders (94%) were stable. The remaining two shoulders dislocated at 2.5 weeks and three months post-operatively, respectively. According to the Neer rating system, there were 13 excellent (40%), ten satisfactory (30%) and ten unsatisfactory results (30%). Revision of hemiarthroplasty or anatomical total shoulder replacement for instability using a reverse design prosthesis gives good short-term results.

Cite this article: Bone Joint J 2013;95-B:668–72.
Effects of selenium coating of orthopaedic implant surfaces on bacterial adherence and osteoblastic cell growth
Authors: Holinka J. , Pilz M. , Kubista B. , Presterl E. , Windhager R.
Published: April 2013

The aim of this study was to evaluate whether coating titanium discs with selenium in the form of sodium selenite decreased bacterial adhesion of Staphylococcus aureus and Staph. epidermidis and impeded osteoblastic cell growth.

In order to evaluate bacterial adhesion, sterile titanium discs were coated with increasing concentrations of selenium and incubated with bacterial solutions of Staph. aureus (ATCC 29213) and Staph. epidermidis (DSM 3269) and stained with Safranin-O. The effect of selenium on osteoblastic cell growth was also observed. The adherence of MG-63 cells on the coated discs was detected by staining with Safranin-O. The proportion of covered area was calculated with imaging software.

The tested Staph. aureus strain showed a significantly reduced attachment on titanium discs with 0.5% (p = 0.011) and 0.2% (p = 0.02) selenium coating. Our test strain from Staph. epidermidis showed a highly significant reduction in bacterial adherence on discs coated with 0.5% (p = 0.0099) and 0.2% (p = 0.002) selenium solution. There was no inhibitory effect of the selenium coating on the osteoblastic cell growth.

Selenium coating is a promising method to reduce bacterial attachment on prosthetic material.

Cite this article: Bone Joint J 2013;95-B:678–82.
GW9508 inhibits insulin secretion by activating ATP-sensitive potassium channels in rat pancreatic β-cells
Authors: Zhao Yu-Feng , Wang Li , Zha Dingjun , Qiao Li , Lu Lianjun , Yu Jun , Qu Ping , Sun Qiang , Qiu Jianhua , Chen Chen
Published: April 2013

GW9508 is an agonist of G protein-coupled receptor 40 (GPR40) that is expressed in pancreatic β-cells and is reported to regulate insulin secretion. However, the effects of GW9508 on pancreatic β-cells in primary culture have not been well investigated. This study measured the acute effects of GW9508 on insulin secretion from rat pancreatic islets in primary culture, and the insulin secretion-related events such as the changes in membrane potential, ATP-sensitive potassium currents (KATPcurrents), and intracellular Ca2+concentrations ([Ca2+]i) of rat islet β-cells were also recorded. GW9508 (10–40 μM) did not influence basal insulin levels at 2 mM glucose, but it (above 20 μM) significantly inhibited 5 and 15 mM glucose-stimulated insulin secretion (GSIS). GW9508 did not inhibit insulin secretion stimulated by tolbutamide, the closer of KATPchannels. GW9508 activated KATPchannels and blocked the membrane depolarization and the increase in [Ca2+]ithat were stimulated by glucose. GW9508 itself stimulated a transient increase in [Ca2+]i, which was fully blocked by depletion of intracellular Ca2+stores with thapsigargin or by inhibition of phospholipase C (PLC) activity with U73122. GW9508-induced activation of KATPchannels was only partly inhibited by U73122 treatment. In conclusion, although it stimulates a transient release of Ca2+from intracellular Ca2+stores via activation of PLC, GW9508 inhibits GSIS by activating KATPchannels probably in a distal step to GPR40 activation in rat β-cells.
The 2013 Thomas Hunt Morgan Medal
Authors: Jinks-Robertson Sue , Hieter Philip
Published: April 2013

The Genetics Society of America annually honors members who have made outstanding contributions to genetics. The Thomas Hunt Morgan Medal recognizes a lifetime contribution to the science of genetics. The Genetics Society of America Medal recognizes particularly outstanding contributions to the science of genetics over the past 32 years. The George W. Beadle Award recognizes distinguished service to the field of genetics and the community of geneticists. The Elizabeth W. Jones Award for Excellence in Education recognizes individuals or groups who have had a significant, sustained impact on genetics education at any level, from kindergarten through graduate school and beyond. The Novitski Prize recognizes an extraordinary level of creativity and intellectual ingenuity in solving significant problems in biological research through the application of genetic methods. We are pleased to announce the 2013 awards.
Medication Errors in the Home: A Multisite Study of Children With Cancer
Authors: Walsh Kathleen E. , Roblin Douglas W. , Weingart Saul N. , Houlahan Kathleen E. , Degar Barbara , Billett Amy , Keuker Christopher , Biggins Colleen , Li Justin , Wasilewski Karen , Mazor Kathleen M.
Published: April 2013

OBJECTIVE:

As home medication use increases, medications previously managed by nurses are now managed by patients and their families. Our objective was to describe the types of errors occurring in the home medication management of children with cancer.

METHODS:

In a prospective observational study at 3 pediatric oncology clinics in the northeastern and southeastern United States, patients undergoing chemotherapy and their parents were recruited from November 2007 through April 2011. We reviewed medical records and checked prescription doses. A trained nurse visited the home, reviewed medication bottles, and observed administration. Two physicians independently made judgments regarding whether an error occurred and its severity. Overall rates of errors were weighted to account for clustering within sites.

RESULTS:

We reviewed 963 medications and observed 242 medication administrations in the homes of 92 patients. We found 72 medication errors. Four errors led to significant patient injury. An additional 40 errors had potential for injury: 2 were life-threatening, 13 were serious, and 25 were significant. Error rates varied between study sites (40–121 errors per 100 patients); the weighted overall rate was 70.2 errors per 100 patients (95% confidence interval [CI]: 58.9–81.6). The weighted rate of errors with injury was 3.6 (95% CI: 1.7–5.5) per 100 patients and with potential to injure the patient was 36.3 (95% CI: 29.3–43.3) per 100 patients. Nonchemotherapy medications were more often involved in an error than chemotherapy.

CONCLUSIONS:

Medication errors were common in this multisite study of outpatient pediatric cancer care. Rates of preventable medication-related injuries in this outpatient population were comparable or higher than those found in studies of hospitalized patients.
Mothers with a Mental Illness: Stressors and Resources for Parenting and Living
Authors: Mowbray Carol , Schwartz Sondra , Bybee Deborah , Spang Jan , Rueda-Riedle Alba , Oyserman Daphna
Published: April 2013

Policy changes as well as improved treatment and rehabilitation practices mean that more women with mental illness are carrying out parenting roles. However, mental-health services have only given limited attention to parenting problems and benefits for clients with psychiatric disabilities. Previous research has focused more on mothers' clinical characteristics, and less on the social and economic contexts in which parenting occurs. The present report involves a large, primarily minority sample of women with serious mental illness who are mothers and who are being served in the public mental-health system of a large urban area. We sought to collect more comprehensive information to better understand their situations and improve service provisions. The women in the study report experiencing severe financial strains and health problems, even when compared with other low-income, urban-based populations. Many also have experienced crises, loss of significant others, assaults, and other negative life events that are very stressful, along with a high number of chronic hassles. They do have resources available to them, through interpersonal supports, religion, and mental-health services. The discussion focuses on implications for micro- and macro-practice to improve these women's lives, their parenting, and the potential outcomes of their children.
Incorporating Gender Issues in Practice with the Satir Growth Model
Authors: Freeman Miriam L.
Published: April 2013

This article reports an investigation of practitioners' views and practices regarding gender and the Satir growth model. Quantitative and qualitative data were used to determine if and how Satir-based practitioners incorporate attention to gender issues in their work. Emergent themes from the data suggest that practitioners incorporate gender in their use of the growth model by (1) paying attention to the societal context in which families are embedded, (2) surfacing and transforming old learnings about gendered roles, and (3) facilitating the creation of egalitarian relationships in families. Specific examples of these themes are given, and guidelines for integrating gender in practice are suggested.