bluuebunny/crossref_metadata_2025 huggingface dataset:
Trade Elasticities, Commodity Prices, and the Global Financial Crisis
Authors: Ketenci Natalya
Published: September 2014

The effect of the global financial crisis on the international trade patterns of developed countries has been one of the main focuses of recent scholarship. However, world trade depends evermore on emerging markets increases every day. Therefore, it is important to study the level of the negative effect of the crisis on emerging economies and the level of their recovery potential. This paper empirically studies the effects of the financial crisis on trade elasticities of BRIICS (Brazil, Russia, India, Indonesia, China, and South Africa) countries and Turkey. The imperfect substitute model (Goldstein & Khan, 1985) for the export and import demand functions is used. Additionally, the extended model is estimated where commodity price index is employed. The autoregressive distributed lag (ARDL) approach to cointegration is applied to test the cointegration relationships between exports and imports and their determinants, and in order to estimate the export and import elasticities in the countries under examination. The empirical results provide enough evidence to conclude that changes in the exchange rate and in commodity prices did not play significant role in export and import demand functions before and after the global financial crisis. However, foreign and domestic incomes are found highly significant and elastic in export and import demand functions, respectively. It is found as well that the global financial crisis had increasing effect on export and import responsiveness to foreign and domestic incomes respectively, except for Turkey and Brazil in the export demand function and South Africa in the import demand function.
The 2007–2008 Global Financial Crisis, and Cross-border Mergers and Acquisitions
Authors: Reddy Kotapati Srinivasa , Nangia Vinay Kumar , Agrawal Rajat
Published: September 2014

Many interdisciplinary studies of the 2007–2008 global financial crisis examine the causes of crisis, corporate governance and firm value, stock market efficiency, new firm registration, macroeconomic performance, and compare this crisis to previous crises. However, we do not find conceptual (empirical) studies that study foreign mergers or acquisitions with respect to the financial crisis. In this exploratory study, we perform an investigation using the UNCTAD’s dataset of worldwide cross-border mergers and acquisitions (CB-M&As). We select 26 countries and employ the adjusted event-study method to find significant difference between the means of pre-crisis period (2004–2006) and post-crisis period (2008–2010) for both sales and purchases in three variables, namely, number of deals, deal value, and average deal value. Our results show that the 2007–2008 global financial crisis has negatively affected both CB-M&A sale and purchase transactions all over the world from 2008 to 2009. We found, however, that after the crisis period, emerging market countries have taken advantage of the attractive asset prices in developed countries and increased their foreign acquisitions. Lastly, we offer “crisis-related CB-M&A propositions” that would facilitate future hypotheses testing, empirical studies, and policy-making research.
Next Steps in TeamSTEPPS®
Authors: Clapper Timothy C.
Published: September 2014

Purpose

The purpose of this article is to propose a strategy for ensuing simulation training following the implementation of a thorough Team Strategies and Tools to Enhance Performance and Patient Safety (TeamSTEPPS®) training initiative. The strategies include observing Teams in the workplace to facilitate the construction of organization-wide, follow-on simulation training.

Design/methodology/approach

A review of organizational change and instructional design practices is presented to facilitate TeamSTEPPS® to its fullest. This article serves as a continuation of steps to full implementation following an initial article introducing TeamSTEPPS® and a second article identifying the challenges and opportunities for success during preliminary organization-wide training.

Findings

TeamSTEPPS® is a patient safety tool developed by the U.S. Department of Defense that is based on four competencies. The TeamSTEPPS® competencies and simulation can be used to create a just culture, which is based on effective teamwork and communication. However, full implementation and facilitation of a just culture requires health care organizations to consider reinforcement and next steps in training, along with a new way of thinking about the use of observation and simulation to facilitate organizational change.

Research limitations/implications

The literature contains large gaps concerning full implementation of TeamSTEPPS®. Very little has been published on how to implement TeamSTEPPS® throughout a health care organization, particularly articles based on good instructional design and organizational change principles. These gaps can lead to piecemeal implementation of TeamSTEPPS® with few positive results for the organization.

Originality/value

Many organizations have implemented TeamSTEPPS®, but have not conducted follow-on training that uses direct observation, debriefing, and simulation to address or strengthen specific behaviors.
Cross-Validation of the JSORRAT-II in Iowa
Authors: Ralston Christopher A. , Epperson Douglas L. , Edwards Sarah R.
Published: September 2014

The predictive validity of the Juvenile Sexual Offense Recidivism Risk Assessment Tool–II (JSORRAT-II) was evaluated using an exhaustive sample of 11- to 17-year-old male juveniles who offended sexually (JSOs) between 2000 and 2006 in Iowa ( n = 529). The validity of the tool in predicting juvenile sexual recidivism was significant (area under the receiver operating characteristic curve [AUC] = .70, 99% confidence interval [CI] = [.60, .81], d = 0.70). Non-significant predictive validity coefficients were observed for the prediction of non-sexual forms of recidivism. Additional analyses were undertaken to test hypotheses about the tool’s performance with various subsamples. The age of the JSO at the time of the index sexual offense and time at risk outside secure facility placements interacted significantly with JSORRAT-II scores to predict juvenile sexual recidivism. The implications of these findings for practice and research on the validation of risk assessment tools are discussed.
Contested norms in new-adopter states: International determinants of LGBT rights legislation
Authors: Ayoub Phillip M.
Published: September 2014

This article is concerned with the question of why lesbian, gay, bisexual, and trans (LGBT) rights legislation is introduced at higher levels in some cases and less so in others. To address this puzzle, the article analyzes changes in LGBT rights legislation across European Union (EU) member states between 1970 and 2009. It focuses on the diffusion of five different categories of such legislation (anti-discrimination, criminal law, partnership, parenting rights, and equal sexual offenses provisions) to new EU member states in Central and Eastern Europe, compared with diffusion patterns in older EU member states. I argue that new-adopter states are more dependent on international resources for making new issues visible and are more inclined to see policy adoption as a means to gain external legitimacy and improve reputation. The analysis reveals that the transnational embeddedness of a state’s LGBT advocacy organizations is a powerful statistical explanation for successful policy diffusion to new EU member states, alongside international channels that lead to LGBT visibility among society and state authorities. In addition to lending cross-national, empirical reinforcement to some of the theoretical expectations regarding the international sources of diffusion, the results suggest variability in the determinants of LGBT policy adoption between the 15 old and 12 new EU states. Domestic factors, particularly economic modernization, are more relevant for policy adoption in the older member states, whereas the newer member states display greater dependence on transnational actors and are more influenced by international channels.
A qualitative analysis of implementing shared decision making in Child and Adolescent Mental Health Services in the United Kingdom: Stages and facilitators
Authors: Abrines-Jaume Neus , Midgley Nick , Hopkins Katy , Hoffman Jasmine , Martin Kate , Law Duncan , Wolpert Miranda
Published: September 2014

Objectives: To explore the implementation of shared decision making (SDM) in Child and Adolescent Mental Health Services (CAMHS), and identify clinician-determined facilitators to SDM. Methods: Professionals from four UK CAMHS tried a range of tools to support SDM. They reflected on their experiences using plan-do-study-act log books. A total of 23 professionals completed 307 logs, which were transcribed and analysed using Framework Analysis in Atlas.Ti. Results: Three states of implementation (apprehension, feeling clunky, and integration) and three aspects of clinician behavior or approach (effort, trust, and flexibility) were identified. Conclusions: Implementation of SDM in CAMHS requires key positive clinician behaviors, including preparedness to put in effort, trust in young people, and use of the approach flexibly. Practice implications: Implementation of SDM in CAMHS is effortful, and while tools may help support SDM, clinicians need to be allowed to use the tools flexibly to allow them to move from a state of apprehension through a sense of feeling “clunky” to integration in practice.
The financial cost of managing tibial plateau fractures at a major trauma centre
Authors: Myatt Richard W , Miles Jack , Matharu Gulraj S , Cockshott Simon , Kendrew Jonathan
Published: September 2014

Introduction:

Tibial plateau fractures can be challenging to manage, and as such, they are often referred to tertiary referral centres for specialist input, and with the advent of Major Trauma Centres, this is likely to increase. The financial implications of this are unknown. The study aims were to: (1) analyse the cost of tibial plateau fracture management at a major trauma centre, (2) identify the proportion each aspect of the admission contributed to overall cost, and (3) investigate how tibial plateau fractures were coded.

Patients and methods:

A retrospective review of all patients presenting between July 2010 and October 2011 with a tibial plateau fracture was performed. Data were collected on all aspects of each patient’s admission. The cost for each part of the admission was obtained from the institution finance department with the total cost of treating tibial plateau fractures in each patient subsequently calculated.

Results:

Forty tibial plateau fractures were included (mean age 43.6 years; 70.0% male). Fractures occurred as a component of polytrauma in 37.5% with operative fixation performed in 65%. Mean total cost of treating tibial plateau fractures was £4941 with ward costs (57.6%) and operative costs (34.1%) accounting for the majority. Mean cost of managing fractures sustained in polytrauma (£3073) remained significantly higher ( p = 0.012) than those sustained in isolation (£1401) when excluding ward costs and adjusting for length of stay. This was true irrespective of Schatzker grade. No specific injury code was available for tibial plateau fractures. In patients sustaining polytrauma, the tibial plateau fracture was never coded as the primary injury, but instead using a subsidiary code, which attracted less remuneration.

Conclusions:

Tibial plateau fractures sustained during polytrauma incurred the highest costs. As ward costs contribute to the majority of overall cost, it is recommended that mechanisms are in place to facilitate early discharge back to referring centres or to provide remuneration for incurred admission costs once definitive fracture fixation has been performed. Hospital coding must be modified to more accurately reflect the injuries sustained.
Accuracy and awareness of lag screw placement when using the dynamic hip screw for fracture fixation
Authors: Matharu Gulraj S , Shahid Mohammad , Pynsent Paul B , Rowlands Tom
Published: September 2014

Introduction

Correct lag screw placement in the femoral head is important to prevent screw cut-out following dynamic hip screw (DHS) fracture fixation. The aim of the study was to determine the accuracy and awareness of lag screw placement when using the DHS for fracture fixation.

Patients and methods

A retrospective radiographic review of 238 DHS procedures (mean age 81.1 years; 76% female) performed at one centre was undertaken to determine the proportion of lag screws placed correctly (tip–apex distance (TAD) less than 25 mm and central femoral head lag screw position in both radiographic views). A questionnaire was also distributed to 102 orthopaedic surgeons to assess awareness of correct lag screw placement.

Results

Mean TAD for 238 procedures was 17.2 mm with specialist registrars performing 74%. Lag screws were correctly placed in 80% ( n = 190) with correct placement independent of surgeon grade ( p = 0.418), AO fracture classification ( p = 0.306) and contralateral femoral neck-shaft angle ( p = 0.748). This remained unchanged when 17 lag screws meeting the recommendations, but with an inferior position on the anteroposterior radiograph, were included as correctly placed. Surgeons correctly defined TAD, stated the recommended TAD and measured TAD correctly in 81%, 81% and 57%, respectively. Correct responses were independent of surgeon grade and number of procedures performed.

Conclusions

Although most lag screws were placed correctly, the questionnaire revealed that almost half of surgeons measured TAD incorrectly. Educating surgeons on the concepts related to correct lag screw placement and acquiring technical skills using surgical simulators may reduce the risk of screw cut-out in their practice.
Review of rollerblading injuries
Authors: Mirhadi Sara , Ashwood Neil , Karagkevrekis Babis
Published: September 2014

Rollerblading is becoming more popular in the UK and this has led to an increase in injuries. Our aim is to review the characteristics of injuries caused by rollerblading, to compare them in children and adults, to identify risk factors associated with such injuries and to review the role of injury prevention strategies.
Digital health care: Cementing centralisation?
Authors: Keen Justin
Published: September 2014

This article reviews large-scale digital developments in the National Health Service in England in recent years and argues that there is a mismatch between digital and organisational thinking and practice. The arguments are based on new institutional thinking, where the digital infrastructure is taken to be an institution, which has been shaped over a long period, and which in turn shapes the behaviour of health professionals, managers and others. Many digital services are still being designed in line with a bureaucratic data processing model. Yet health services are increasingly based on a network model, where health professionals and service managers require information systems that allow them to manage risks proactively and to coordinate multiple services on behalf of patients. This article further argues that the data processing model is being reinforced by Open Data policies and by related developments in the acquisition of genomic and telehealth data, suggesting that the mismatch will persist. There is, therefore, an ongoing tension between frontline and central objectives for digital services. It may be that the tension can only be resolved when – or if – there is trust between the interested parties.
News programs: Designing MSNBC.com’s online interfaces
Authors: Braun Joshua A
Published: September 2014

In this essay, I use Law’s framework of heterogeneous engineering in tandem with insights from other sociologists of systems and scholarship on organizations, as a springboard to examine a number of digital artifacts assembled by the MSNBC Digital Network over the period 2007 through 2010 and to explore the manner in which a wide variety of values, interests, and concerns became ‘invested and contested’ in their design. Specifically, this article, the result of 5 weeks of interviewing and field observation at MSNBC.com, MSNBC TV, and National Broadcasting Corporation (NBC) News’ various online offices, explores the backstories of two seemingly mundane interfaces used by NBC News’ Web properties during that period, both of which are revealed to be particularly dynamic, heterogeneous, contingent, and consequential.
Infoboxes and cleanup tags: Artifacts of Wikipedia newsmaking
Authors: Ford Heather
Published: September 2014

Wikipedians use a number of editorial elements, including infoboxes and cleanup tags to coordinate work in the first stage of articles related to breaking news topics. When inserted into an article, these objects are intended to simultaneously notify editors about missing or weak elements of the article and to add articles to particular categories of work. This categorization practice enables editors to collaborate iteratively with one another because each object signals work that needs to be done by others in order to fill in the gaps of the current content. In addition to this functional value, however, categorization also has a number of symbolic and political consequences. Editors are engaged in a continual practice of iterative summation that contributes to an active construction of the event as it happens rather than a mere assembling of ‘reliable sources’. The deployment and removal of cleanup tags can be seen as an act of power play between editors that affects readers’ evaluation of the article’s content. Infoboxes are similar sites of struggle whose deployment and development result in an erasure of the contradictions and debates that gave rise to them. These objects illuminate how this novel journalistic practice has important implications for the way that political events are represented.
Effective sample size for computing prior hyperparameters in Bayesian phase I–II dose-finding
Authors: Thall Peter F , Herrick Richard C , Nguyen Hoang Q , Venier John J , Norris J Clift
Published: September 2014

Background:

The efficacy–toxicity trade-off based design is a practical Bayesian phase I–II dose-finding methodology. Because the design’s performance is very sensitive to prior hyperparameters and the shape of the target trade-off contour, specifying these two design elements properly is essential.

Purpose:

The goals are to provide a method that uses elicited mean outcome probabilities to derive a prior that is neither overly informative nor overly disperse, and practical guidelines for specifying the target trade-off contour.

Methods:

A general algorithm is presented that determines prior hyperparameters using least squares penalized by effective sample size. Guidelines for specifying the trade-off contour are provided. These methods are illustrated by a clinical trial in advanced prostate cancer. A new version of the efficacy–toxicity program is provided for implementation.

Results:

Together, the algorithm and guidelines provide substantive improvements in the design’s operating characteristics.

Limitations:

The method requires a substantial number of elicited values and design parameters, and computer simulations are required to obtain an acceptable design.

Conclusion:

The two key improvements greatly enhance the efficacy–toxicity design’s practical usefulness and are straightforward to implement using the updated computer program. The algorithm for determining prior hyperparameters to ensure a specified level of informativeness is general, and may be applied to models other than that underlying the efficacy–toxicity method.
Quantitative comparison of Hybrid III and National Operating Committee on Standards for Athletic Equipment headform shape characteristics and implications on football helmet fit
Authors: Cobb Bryan R , MacAlister Anna , Young Tyler J , Kemper Andrew R , Rowson Steven , Duma Stefan M
Published: September 2014

Laboratory tests in which dummy headforms are used to evaluate helmet performance must be representative of real-world conditions to ensure helmets perform well in the field. The objective of this study was to quantify shape differences that may affect helmet fit between two dummy headforms commonly used for football helmet testing. Point-cloud models of a 50th percentile male Hybrid III headform and a medium NOCSAE headform were generated using a coordinate measuring machine. The headforms were optimally aligned and shape comparisons were made in the mid-sagittal plane, three coronal planes, and 3D. Planar and 3D differences were quantified by comparing maximum (MRD) and root-mean-square (RMSD) radial deviations. Minor differences were observed in the upper skull contours of all planar cross-sections, where MRDs were less than 3.5 mm and RMSDs were less than 1.7 mm. Larger deviations were observed in other regions including the jaw in the anterior coronal plane, where the MRD was 6.6 mm and the RMSD deviation was 4.5 mm. Substantial differences were noted between the Hybrid III and NOCSAE at the base of the skull, cheeks, jaw and chin. The headforms were also compared to a head model based on medical imaging of a human subject, which the NOCSAE matched more closely than the Hybrid III. The data presented in this study show that the Hybrid III and NOCSAE headforms have substantial shape differences in several regions that are important for helmet fit, possibly making the NOCSAE a better option for realistic helmet fit.
Computer-aided design to support fabrication of wrist splints using 3D printing: A feasibility study
Authors: Paterson Abby M , Donnison Ella , Bibb Richard J , Ian Campbell R
Published: September 2014

Introduction

Issues contributing to poor patient compliance for splint wear include poor aesthetics, fit and performance. This paper describes a novel digitised splinting process using 3D printing in an attempt to overcome these issues. The output of the investigation was the creation of a specialised computer-aided design software workflow to support 3D printing, developed specifically for splinting practitioners in the UK, to enable them to design splints themselves for each individual patient.

Method

A small-scale feasibility study was done, based on the current splinting process. A thorough literature review and physical engagement in current splinting practice was performed, highlighting key requirements for successful splint fabrication. Key requirements were then replicated in a virtual software environment. Opportunities for integrating new, novel features were explored. The key requirements were then refined into a specialised software workflow to replicate the splinting process. The specialised software was then evaluated by 10 practitioners. User trials of the software were performed, followed by semi-structured interviews. Audio recordings were transcribed and then coded to establish similar trends of opinions, and areas for future research. No patients or vulnerable participants were involved in the study.

Results

All participants were able to use and navigate around the software prototype with relative ease. Strengths included potential simplicity in modelling more complex splints, but several areas for future research are identified, including cost analysis and materials development.

Discussion

The digitised splinting process shows promise for the benefit of both practitioners and their patients, provided that future research and investment can overcome current limitations.
Neoliberal reform and protest in Latin American democracies: A replication and correction
Authors: Solt Frederick , Kim Dongkyu , Lee Kyu Young , Willardson Spencer , Kim Seokdong
Published: September 2014

Do neoliberal economic reforms in Latin American democracies mobilize citizens to overcome their collective action problems and protest? A recent addition to the scholarship on this crucial question of the relationship of markets and politics, Bellinger and Arce (2011), concludes that economic liberalization does have this effect, working to repoliticize collective actors and reinvigorate democracy. We reexamine the article’s analyses and demonstrate that they misinterpret the marginal effect of the variables of theoretical interest. Thus, the article’s optimistic claims about the consequences for democracy of economic liberalization in the region are not supported by its own empirical results. It is argued here that its results suggest instead that protests became more common in autocracies when they moved away from markets. Rather than speaking to how people have mobilized to protest against liberal reforms in Latin America’s democracies, the work’s analyses illuminate only when people protested against the region’s dictatorships.
Revisiting Racial/Ethnic Composition Effects in a Multicultural Society
Authors: Stansfield Richard
Published: September 2014

In this article, the relationship between racial/ethnic composition and violence is revisited. This includes efforts to conduct a deeper exploration of the ethnic composition effects of discrete Latino-origin populations. This is an important extension for a number of reasons. First, recent research has demonstrated the dangers of pan-ethnic classifications in the study of race, ethnicity, and crime. Different histories of migration, settlement, opportunity, and intergenerational advancement have produced different levels of successful integration for some groups relative to others, with different implications for crime. One of the distinguishing features of the contemporary Latino population is a disproportionately young average age. Specifically, Latinos in the United States include a higher percentage of adolescent and young adults than the national average—a period of the life course where criminal behavior tends to peak. Thus, I also examine how racial and ethnic composition and change in these areas is associated with variation in violence perpetrated by youth and emerging adults specifically.
Effect of dynamic plastic deformation on microstructure and annealing behaviour of modified 9Cr−1Mo steel
Authors: Zhang Z. B. , Mishin O. V. , Tao N. R. , Pantleon W.
Published: September 2014

The effect of dynamic plastic deformation on the microstructure of a modified 9Cr−1Mo steel has been investigated in comparison with the effect of quasi-static compression. It is found that the boundary spacing after dynamic plastic deformation is smaller and the hardness is higher than those after quasi-static compression. The microstructure after dynamic plastic deformation is however less stable than the microstructure after quasi-static compression. Annealing at 675 and 700°C leads to structural coarsening and recrystallisation in each sample, but with recrystallisation occurring faster in the sample annealed after dynamic plastic deformation. The lower thermal stability of the microstructure produced by dynamic plastic deformation is attributed to a higher driving force for recrystallisation in the dynamically deformed material.
Non-invasive temperature measurement and control techniques under thermomechanical fatigue loading
Authors: Jones J. , Brookes S. P. , Whittaker M. T. , Lancaster R. J.
Published: September 2014

A non-invasive temperature measurement, control and profiling technique has been investigated for use with thermomechanical fatigue loading. The technique utilises an infrared thermography camera and Rolls–Royce developed thermal paint to control and monitor cyclic temperature. Thermal paint is used to maintain a stable surface emissivity upon the test piece. The accuracy of the technique is compared against type N thermocouples and a pyrometer for both temperature control and monitoring purposes. Diverse test specimen geometries and alloy compositions are used over a 100–700°C temperature range. Effects on temperature measurement accuracy such as thermocouple shadowing are highlighted and quantified. The non-invasive technique has proved accurate to within ±2°C of the reference thermocouples when in combination with the thermal paint coating.
State of the art: pulmonary hypertension
Authors: Samillan Victor J. , Peacock Andrew J.
Published: September 2014

Key points

Pulmonary arterial hypertension is still a chronic and incurable disease

The most common mutation found in familial pulmonary arterial hypertension is a defect in the bone morphogenetic protein receptor 2 gene

Usually the final stage of the disease is right heart failure

Educational aims

To provide definitions and diagnostic methods for pulmonary hypertension

To provide a general classification of pulmonary hypertension

To provide an overview of the currently available treatments

To provide a future vision of next-generation treatments
“Breathe Clean Air”: the role of physicians and healthcare professionals
Authors: Künzli Nino , Rapp Regula , Perez Laura
Published: September 2014

The health effects of air pollution have a lot in common with those related to active or passive smoking. However, environmental problems pose a rather different set of challenges to physicians and other healthcare professionals.

Four target levels of action may result in a reduction of the health impact of air pollution. The first two levels act on the environment rather than the individual: 1) abatement of ambient air pollution at the source to improve ambient air quality; and 2) reduction of pollution in the indoor environments where people spend most of their time. The other two downstream strategies depend entirely on the individual: 3) individual action to reduce personal exposure or dose; and 4) treatments taken to modify personal responses to air pollution, and/or to strengthen defence mechanisms.
New iteration scheme for numerical reckoning fixed points of nonexpansive mappings
Authors: Thakur Dipti , Thakur Balwant Singh , Postolache Mihai
Published: September 2014

The purpose of this paper is to introduce a new three step iteration scheme for approximation of fixed points of the nonexpansive mappings. We show that our iteration process is faster than all of the Picard, the Mann, the Agarwal et al., and the Abbas et al. iteration processes. We support our analytic proof by a numerical example in which we approximate the fixed point by a computer using Matlab program. We also prove some weak convergence and strong convergence theorems for the nonexpansive mappings.

MSC:47H09, 47H10.
Algorithms with strong convergence for the split common solution of the feasibility problem and fixed point problem
Authors: Yao Yonghong , Agarwal Ravi P , Postolache Mihai , Liou Yeong-Cheng
Published: September 2014

The purpose of this paper is to study the split feasibility problem and fixed point problem involved in the pseudocontractive mappings. We construct an iterative algorithm and prove its strong convergence.

MSC:47J25, 47H09, 65J15, 90C25.
Fixed point results, generalized Ulam-Hyers stability and well-posedness via α-admissible mappings in b-metric spaces
Authors: Phiangsungnoen Supak , Sintunavarat Wutiphol , Kumam Poom
Published: September 2014

In this paper, we prove the existence and uniqueness of a fixed point for some new classes of contractive mappings via α-admissible mappings in the framework of b-metric spaces. We also present an example to illustrate the usability of the obtained results. The generalized Ulam-Hyers stability and well-posedness of a fixed point equation via α-admissible mappings in b-metric spaces are given.

MSC:46S40, 47S40, 47H10.
Preclinical Toxicity Evaluation of AAV for Pain: Evidence from Human AAV Studies and from the Pharmacology of Analgesic Drugs
Authors: Pleticha Josef , Heilmann Lukas F , Evans Christopher H , Asokan Aravind , Samulski Richard Jude , Beutler Andreas S
Published: September 2014

Gene therapy with adeno-associated virus (AAV) has advanced in the last few years from promising results in animal models to >100 clinical trials (reported or under way). While vector availability was a substantial hurdle a decade ago, innovative new production methods now routinely match the scale of AAV doses required for clinical testing. These advances may become relevant to translational research in the chronic pain field. AAV for pain targeting the peripheral nervous system was proven to be efficacious in rodent models several years ago, but has not yet been tested in humans. The present review addresses the steps needed for translation of AAV for pain from the bench to the bedside focusing on pre-clinical toxicology. We break the potential toxicities into three conceptual categories of risk: First, risks related to the delivery procedure used to administer the vector. Second, risks related to AAV biology, i.e., effects of the vector itself that may occur independently of the transgene. Third, risks related to the effects of the therapeutic transgene. To identify potential toxicities, we consulted the existing evidence from AAV gene therapy for other nervous system disorders (animal toxicology and human studies) and from the clinical pharmacology of conventional analgesic drugs. Thereby, we identified required preclinical studies and charted a hypothetical path towards a future phase I/II clinical trial in the oncology-palliative care setting.
Differentially-expressed genes in rice infected by Xanthomonas oryzae pv. oryzae relative to a flagellin-deficient mutant reveal potential functions of flagellin in host–pathogen interactions
Authors: Yu Chao , Chen Huamin , Tian Fang , Leach Jan E , He Chenyang
Published: September 2014

Background

Plants have evolved a sensitive defense response system that detects and recognizes various pathogen-associated molecular patterns (PAMPs) (e.g. flagellin) and induces immune responses to protect against invasion. Transcriptional responses in rice to PAMPs produced by Xanthomonas oryzae pv. oryzae (Xoo), the bacterial blight pathogen, have not yet been defined.

Results

We characterized transcriptomic responses in rice inoculated with the wildtype (WT) Xoo and flagellin-deficient mutant ∆fliC through RNA-seq analysis. Digital gene expression (DGE) analysis based on Solexa/Illumina sequencing was used to investigate transcriptomic responses in 30 day-old seedlings of rice (Oryza sativa L. cv. Nipponbare). 1,680 genes were differentially-expressed (DEGs) in rice inoculated with WT relative to ∆fliC; among which 1,159 genes were up-regulated and 521 were down-regulated. Expression patterns of 12 randomly-selected DEGs assayed by quantitative real time PCR (qRT-PCR) were similar to those detected by DGE analyses, confirming reliability of the DGE data. Functional annotations revealed the up-regulated DEGs are involved in the cell wall, lipid and secondary metabolism, defense response and hormone signaling, whereas the down-regulated ones are associated with photosynthesis. Moreover, 57 and 21 specifically expressed genes were found after WT and ∆fliC treatments, respectively.

Conclusions

DEGs were identified in rice inoculated with WT Xoo relative to ∆fliC. These genes were predicted to function in multiple biological processes, including the defense response and photosynthesis in rice. This study provided additional insights into molecular basis of rice response to bacterial infection and revealed potential functions of bacterial flagellin in the rice-Xoo interactions.
Aluminum induces rapidly mitochondria-dependent programmed cell death in Al-sensitive peanut root tips
Authors: Huang Wen-Jing , Oo Thet Lwin , He Hu-Yi , Wang Ai-Qin , Zhan Jie , Li Chuang-Zhen , Wei Shan-Qing , He Long-Fei
Published: September 2014

Background

Although many studies suggested that aluminum (Al) induced programmed cell death (PCD) in plants, the mechanism of Al-induced PCD and its effects in Al tolerance is limited. This study was to investigate the mechanism and type of Al induced PCD and the relationship between PCD and Al tolerance.

Results

In this study, two genotypes of peanut 99-1507 (Al tolerant) and ZH2 (Al sensitive) were used to investigate Al-induced PCD. Peanut root growth inhibition induced by AlCl3 was concentration and time-dependent in two peanut varieties. AlCl3 at 100 μM could induce rapidly peanut root tip PCD involved in DNA cleavage, typical apoptotic chromatin condensation staining with DAPI, apoptosis related gene Hrs203j expression and cytochrome C (Cyt c) release from mitochondria to cytosol. Caspase3-like protease was activated by Al; it was higher in ZH2 than in 99-1507. Al increased the opening of mitochondrial permeability transition pore (MPTP), decreased inner membrane potential (ΔΨm) of mitochondria. Compared with the control, Al stress increased O2
•- and H2O2 production in mitochondria. Reactive oxygen species (ROS) burst was produced at Al treatment for 4 h.

Conclusions

Al-induced PCD is earlier and faster in Al-sensitive peanut cultivar than in Al-tolerant cultivar. There is a negative relationship between PCD and Al resistance. Mitochondria- dependence PCD was induced by Al and ROS was involved in this process. The mechanism can be explained by the model of acceleration of senescence under Al stress.
Artificial viscosity in comoving curvilinear coordinates: towards a differential geometrically consistent implicit advection scheme
Authors: Höller Harald , Koskela Antti , Dorfi Ernst , Benger Werner
Published: September 2014

We propose a modification for the tensor of artificial viscosity employable for generally comoving, curvilinear grids. We present a strong conservation form for the equations of radiation hydrodynamics for studying nonlinear pulsations of stars. However, the modification we propose is of general mathematical nature. We study a differential geometrically consistent artificial viscosity analytically and visualize a comparison of our approach to previous implementations by applying it to a simple self-similar velocity field which has a direct application in stars as the fundamental mode of pulsation is radial. We first give a general introduction to artificial viscosity and motivate its application in numerical computations. We then show how a tensor of artificial viscosity has to be designed when going beyond common static Eulerian or Lagrangian comoving rectangular grids. We derive and state the modified equations which include metrical terms that adjust the isotropic (pressure) part of the tensor of artificial viscosity.
Very small embryonic-like stem cells are involved in regeneration of mouse pancreas post-pancreatectomy
Authors: Bhartiya Deepa , Mundekar Akash , Mahale Vaibhav , Patel Hiren
Published: September 2014

Introduction

Despite numerous research efforts, mechanisms underlying regeneration of pancreas remains controversial. Views are divided whether stem cells are involved during pancreatic regeneration or it involves duplication of pre-existing islets or ductal cells or whether pancreatic islet numbers are fixed by birth or they renew throughout life. Pluripotent embryonic stem (ES) and induced pluripotent stem (iPS) cells have been used by several groups to regenerate diabetic mouse pancreas but the beneficial effects are short-lived. It has been suggested that cells obtained after directed differentiation of ES/iPS cells resemble fetal and not their adult counterparts; thus are functionally different and may be of little use to regenerate adult pancreas. A novel population of pluripotent very small embryonic-like stem cells (VSELs) exists in several adult body tissues in both mice and humans. VSELs have been reported in the mouse pancreas, and nuclear octamer-binding transcription factor 4 (OCT-4) positive, small-sized cells have also been detected in human pancreas. VSELs are mobilized into peripheral blood in streptozotocin treated diabetic mice and also in patients with pancreatic cancer. This study aimed to evaluate whether VSELs are involved during regeneration of adult mouse pancreas after partial pancreatectomy.

Methods

Mice were subjected to partial pancreatectomy wherein almost 70% of pancreas was surgically removed and residual pancreas was studied on Days 1, 3 and 5 post-surgery.

Results

VSELs were detected in Hematoxylin and Eosin stained smears of pancreatic tissue as spherical, small sized cells with a large nucleus surrounded by a thin rim of cytoplasm and could be sorted as LIN-/CD45-/SCA-1+ cells by flow cytometry. Results reveal that although neutrophils with multi-lobed nuclei are mobilized into the pancreas on day 1 after pancreatectomy, by day 5 VSELs with spherical nuclei, high nucleo-cytoplasmic ratio and nuclear OCT-4 are mobilized into the residual pancreas. VSELs undergo differentiation and give rise to PDX-1 and OCT-4 positive progenitors which possibly regenerate both acinar cells and islets.

Conclusions

Results provide direct evidence supporting the presence of VSELs in adult mouse pancreas and their role during regeneration. VSELs are an interesting alternative to ES/iPS cells to regenerate a diabetic pancreas in future.
Understanding Early Elementary Children's Conceptual Knowledge of Plant Structure and Function through Drawings
Authors: Anderson Janice L. , Ellis Jane P. , Jones Alan M.
Published: September 2014

This study examined children's drawings to explain children's conceptual understanding of plant structure and function. The study explored whether the children's drawings accurately reflect their conceptual understanding about plants in a manner that can be interpreted by others. Drawing, survey, interview, and observational data were collected from 182 students in grades K and 1 in rural southeastern United States. Results demonstrated the children held a wide range of conceptions concerning plant structure and function. These young children held very simple ideas about plants with respect to both their structure and function. Consistent with the drawings, the interviews presented similar findings.
Effects of a Research-Infused Botanical Curriculum on Undergraduates’ Content Knowledge, STEM Competencies, and Attitudes toward Plant Sciences
Authors: Ward Jennifer Rhode , Clarke H. David , Horton Jonathan L.
Published: September 2014

In response to the American Association for the Advancement of Science's Vision and Change in Undergraduate Biology Education initiative, we infused authentic, plant-based research into majors’ courses at a public liberal arts university. Faculty members designed a financially sustainable pedagogical approach, utilizing vertically integrated curricular modules based on undergraduate researchers’ field and laboratory projects. Our goals were to 1) teach botanical concepts, from cells to ecosystems; 2) strengthen competencies in statistical analysis and scientific writing; 3) pique plant science interest; and 4) allow all undergraduates to contribute to genuine research. Our series of inquiry-centered exercises mitigated potential faculty barriers to adopting research-rich curricula, facilitating teaching/research balance by gathering publishable scholarly data during laboratory class periods. Student competencies were assessed with pre- and postcourse quizzes and rubric-graded papers, and attitudes were evaluated with pre- and postcourse surveys. Our revised curriculum increased students’ knowledge and awareness of plant science topics, improved scientific writing, enhanced statistical knowledge, and boosted interest in conducting research. More than 300 classroom students have participated in our program, and data generated from these modules’ assessment allowed faculty and students to present 28 contributed talks or posters and publish three papers in 4 yr. Future steps include analyzing the effects of repeated module exposure on student learning and creating a regional consortium to increase our project's pedagogical impact.
Introductory Biology Students’ Conceptual Models and Explanations of the Origin of Variation
Authors: Speth Elena Bray , Shaw Neil , Momsen Jennifer , Reinagel Adam , Le Paul , Taqieddin Ranya , Long Tammy
Published: September 2014

Mutation is the key molecular mechanism generating phenotypic variation, which is the basis for evolution. In an introductory biology course, we used a model-based pedagogy that enabled students to integrate their understanding of genetics and evolution within multiple case studies. We used student-generated conceptual models to assess understanding of the origin of variation. By midterm, only a small percentage of students articulated complete and accurate representations of the origin of variation in their models. Targeted feedback was offered through activities requiring students to critically evaluate peers’ models. At semester's end, a substantial proportion of students significantly improved their representation of how variation arises (though one-third still did not include mutation in their models). Students’ written explanations of the origin of variation were mostly consistent with their models, although less effective than models in conveying mechanistic reasoning. This study contributes evidence that articulating the genetic origin of variation is particularly challenging for learners and may require multiple cycles of instruction, assessment, and feedback. To support meaningful learning of the origin of variation, we advocate instruction that explicitly integrates multiple scales of biological organization, assessment that promotes and reveals mechanistic and causal reasoning, and practice with explanatory models with formative feedback.
The Teaching Practices Inventory: A New Tool for Characterizing College and University Teaching in Mathematics and Science
Authors: Wieman Carl , Gilbert Sarah
Published: September 2014

We have created an inventory to characterize the teaching practices used in science and mathematics courses. This inventory can aid instructors and departments in reflecting on their teaching. It has been tested with several hundred university instructors and courses from mathematics and four science disciplines. Most instructors complete the inventory in 10 min or less, and the results allow meaningful comparisons of the teaching used for the different courses and instructors within a department and across different departments. We also show how the inventory results can be used to gauge the extent of use of research-based teaching practices, and we illustrate this with the inventory results for five departments. These results show the high degree of discrimination provided by the inventory, as well as its effectiveness in tracking the increase in the use of research-based teaching practices.
Out of the niche: exploring unknown pathways
Authors: Moore Kateri , Cossu Giulio
Published: September 2014

In May 2014, approximately 200 stem cell scientists from all over world gathered near Copenhagen in Denmark to participate in ‘The Stem Cell Niche’, part of the Copenhagen Bioscience Conferences series. The meeting covered an array of different stem cell systems from pluripotent stem cells and germ cells to adult stem cells of the lung, liver, muscle, bone and many more. In addition to the stem cell niche, the meeting focused on a number of cutting edge topics such as cell fate transitions and lineage reprogramming, as well as stem cells in ageing and disease, including cancer. This Meeting review describes the exciting work that was presented and some of the themes that emerged from this excellent meeting.