bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preclinical evaluation of intravenous NAX 810‐2, a novel GalR2‐preferring analog, for anticonvulsant efficacy and pharmacokinetics
Authors: Metcalf Cameron S. , Klein Brian D. , McDougle Daniel R. , Zhang Liuyin , Kaufmann Dan , Bulaj Grzegorz , White H. Steve 
Published: January 2017

SummaryObjectivePotential clinical utility of galanin or peptidic analogs has been hindered by poor metabolic stability, lack of brain penetration, and hyperglycemia due to galanin receptor subtype 1 (GalR1) activation. NAX 810‐2, a galanin receptor subtype 2 (GalR2)‐preferring galanin analog, possesses 15‐fold greater affinity for GalR2 over GalR1 and protects against seizures in the mouse 6 Hz, corneal kindling, and Frings audiogenic seizure models. The purpose of these studies was to further evaluate the preclinical efficacy and pharmacokinetics of NAX 810‐2 in mice.MethodsNAX 810‐2 was administered by intravenous (i.v.; tail vein, bolus) injection to fully kindled (corneal kindling assay) or naive CF‐1 mice (6 Hz assay and pharmacokinetic studies). Plasma NAX 810‐2 levels were determined from trunk blood samples. NAX 810‐2 was also added to human plasma at various concentrations for determination of plasma protein binding.ResultsIn the mouse corneal kindling model, NAX 810‐2 dose‐dependently blocked seizures following intravenous administration (median effective dose [ED50], 0.5 mg/kg). In the mouse 6 Hz (32 mA) seizure model, it was demonstrated that NAX 810‐2 dose‐dependently blocked seizures following bolus administration (0.375–1.5 mg/kg, i.v.; ED50, 0.7 mg/kg), with a time‐to‐peak effect of 0.5 h posttreatment. Motor impairment was observed at 1.5 mg/kg, i.v., whereas one‐half of this dose, 0.75 mg/kg, i.v., was maximally effective in the 6 Hz test. Plasma levels of NAX 810‐2 show linear pharmacokinetics following intravenous administration and a half‐life of 1.2 h. Functional agonist activity studies demonstrate that NAX 810‐2 effectively activates GalR2 at therapeutic concentrations.SignificanceThese studies further suggest the potential utility of NAX 810‐2 as a novel therapy for epilepsy.
A systematic review of economic evaluations of treatments for patients with epilepsy
Authors: Wijnen Ben F.M. , van Mastrigt Ghislaine A.P.G. , Evers Silvia M.A.A. , Gershuni Olga , Lambrechts Danielle A.J.E. , Majoie Marian H.J.M. , Postulart Debby , Aldenkamp Bert A.P. , de Kinderen Reina J.A. 
Published: January 2017

SummaryThe increasing number of treatment options and the high costs associated with epilepsy have fostered the development of economic evaluations in epilepsy. It is important to examine the availability and quality of these economic evaluations and to identify potential research gaps. As well as looking at both pharmacologic (antiepileptic drugs [AEDs]) and nonpharmacologic (e.g., epilepsy surgery, ketogenic diet, vagus nerve stimulation) therapies, this review examines the methodologic quality of the full economic evaluations included. Literature search was performed in MEDLINE, EMBASE, NHS Economic Evaluation Database (NHS EED), Econlit, Web of Science, and CEA Registry. In addition, Cochrane Reviews, Cochrane DARE and Cochrane Health Technology Assessment Databases were used. To identify relevant studies, predefined clinical search strategies were combined with a search filter designed to identify health economic studies. Specific search strategies were devised for the following topics: (1) AEDs, (2) patients with cognitive deficits, (3) elderly patients, (4) epilepsy surgery, (5) ketogenic diet, (6) vagus nerve stimulation, and (7) treatment of (non)convulsive status epilepticus. A total of 40 publications were included in this review, 29 (73%) of which were articles about pharmacologic interventions. Mean quality score of all articles on the Consensus Health Economic Criteria (CHEC)‐extended was 81.8%, the lowest quality score being 21.05%, whereas five studies had a score of 100%. Looking at the Consolidated Health Economic Evaluation Reporting Standards (CHEERS), the average quality score was 77.0%, the lowest being 22.7%, and four studies rated as 100%. There was a substantial difference in methodology in all included articles, which hampered the attempt to combine information meaningfully. Overall, the methodologic quality was acceptable; however, some studies performed significantly worse than others. The heterogeneity between the studies stresses the need to define a reference case (e.g., how should an economic evaluation within epilepsy be performed) and to derive consensus on what constitutes “standard optimal care.”
Contrasting growth forecasts across the geographical range of Scots pine due to altitudinal and latitudinal differences in climatic sensitivity
Authors: Matías Luis , Linares Juan C. , Sánchez‐Miranda Ángela , Jump Alistair S. 
Published: January 2017

AbstractOngoing changes in global climate are altering ecological conditions for many species. The consequences of such changes are typically most evident at the edge of a species’ geographical distribution, where differences in growth or population dynamics may result in range expansions or contractions. Understanding population responses to different climatic drivers along wide latitudinal and altitudinal gradients is necessary in order to gain a better understanding of plant responses to ongoing increases in global temperature and drought severity. We selected Scots pine (Pinus sylvestrisL.) as a model species to explore growth responses to climatic variability (seasonal temperature and precipitation) over the last century through dendrochronological methods. We developed linear models based on age, climate and previous growth to forecast growth trends up to year 2100 using climatic predictions. Populations were located at the treeline across a latitudinal gradient covering the northern, central and southernmost populations and across an altitudinal gradient at the southern edge of the distribution (treeline, medium and lower elevations). Radial growth was maximal at medium altitude and treeline of the southernmost populations. Temperature was the main factor controlling growth variability along the gradients, although the timing and strength of climatic variables affecting growth shifted with latitude and altitude. Predictive models forecast a general increase in Scots pine growth at treeline across the latitudinal distribution, with southern populations increasing growth up to year 2050, when it stabilizes. The highest responsiveness appeared at central latitude, and moderate growth increase is projected at the northern limit. Contrastingly, the model forecasted growth declines at lowland‐southern populations, suggesting an upslope range displacement over the coming decades. Our results give insight into the geographical responses of tree species to climate change and demonstrate the importance of incorporating biogeographical variability into predictive models for an accurate prediction of species dynamics as climate changes.
Moving beyond presence and absence when examining changes in species distributions
Authors: Ashcroft Michael B. , King Diana H. , Raymond Ben , Turnbull Johanna D. , Wasley Jane , Robinson Sharon A. 
Published: January 2017

AbstractSpecies distributions are often simplified to binary representations of the ranges where they are present and absent. It is then common to look for changes in these ranges as indicators of the effects of climate change, the expansion or control of invasive species or the impact of human land‐use changes. We argue that there are inherent problems with this approach, and more emphasis should be placed on species relative abundance rather than just presence. The sampling effort required to be confident of absence is often impractical to achieve, and estimates of species range changes based on survey data are therefore inherently sensitive to sampling intensity. Species niches estimated using presence‐absence or presence‐only models are broader than those for abundance and may exaggerate the viability of small marginal sink populations. We demonstrate that it is possible to transform models of predicted probability of presence to expected abundance if the sampling intensity is known. Using case studies of Antarctic mosses and temperate rain forest trees, we demonstrate additional insights into biotic change that can be gained using this method. While species becoming locally extinct or colonising new areas are extreme and obviously important impacts of global environmental change, changes in abundance could still signal important changes in biological systems and be an early warning indicator of larger future changes.
How lay people understand and make sense of personalized disease risk information
Authors: Damman Olga C. , Bogaerts Nina M. M. , van den Haak Maaike J. , Timmermans Danielle R. M. 
Published: January 2017

AbstractBackgroundDisease risk calculators are increasingly web‐based, but previous studies have shown that risk information often poses problems for lay users.ObjectiveTo examine how lay people understand the result derived from an online cardiometabolic risk calculator.DesignA qualitative study was performed, using the risk calculator in the Dutch National Prevention Program for cardiometabolic diseases. The study consisted of three parts: (i) attention: completion of the risk calculator while an eye tracker registered eye movements; (ii) recall: completion of a recall task; and (iii) interpretation: participation in a semi‐structured interview.Setting and participantsWe recruited people from the target population through an advertisement in a local newspaper; 16 people participated in the study, which took place in our university laboratory.ResultsEye‐tracking data showed that participants looked most extensively at numerical risk information. Percentages were recalled well, whereas natural frequencies and verbal labels were remembered less well. Five qualitative themes were derived from the interview data: (i) numerical information does not really sink in; (ii) the verbal categorical label made no real impact on people; (iii) people relied heavily on existing knowledge and beliefs; (iv) people zoomed in on risk factors, especially family history of diseases; and (v) people often compared their situation to that of their peers.Discussion and conclusionAlthough people paid attention to and recalled the risk information to a certain extent, they seemed to have difficulty in properly using this information for interpreting their risk.
Understanding external cervical resorption patterns in endodontically treated teeth
Authors: Mavridou A.‐M. , Hauben E. , Wevers M. , Schepers E. , Bergmans L. , Lambrechts P. 
Published: January 2017

AbstractAimTo understand the patterns of external cervical resorption (ECR) in endodontically treated teeth. To compare characteristics and mechanisms of ECR in root filled teeth with those established in teeth with vital pulps.MethodologySeven cases of endodontically treated permanent teeth displaying ECR were investigated. ECR diagnosis was based on clinical findings and radiographic examination with cone‐beam computed tomography. The extracted teeth were further analysed by a nano‐focus computed tomographic (nano‐CT) system, hard‐tissue histology and scanning electron microscopy (SEM). To make a comparison with teeth with vital pulps, representative cases with ECR were also included.ResultsAll endodontically treated teeth had a similar ECR pattern. This pattern reflected many similarities to that seen in teeth with vital pulps; that is, three stages were observed namely initiation, resorption and repair. In particular, during the initiation stage (1st stage), the resorption started below the gingival epithelial attachment, at the level of cementum. In the resorption stage (2nd stage), ECR spreads towards the treated pulp space and in a coronal–apical direction, creating multiple resorption channels. The pulp and the pericanalar resorption resistant sheet (PRRS) had been removed during root canal treatment and thus offered no retarding or defence mechanism towards ECR. In the reparative stage (3rd stage), reparative hard‐tissue formation occurred at a localized scale.ConclusionsSimilar ECR patterns were observed in all examined teeth. These patterns consisted of an initiation, a resorption and a reparative stage. Some differences were noticed between endodontically treated and teeth with vital pulps, mainly in the resorption and reparative stages. The resorption stage in root filled teeth was more intense than the repair stage, as many clastic cells and abundant granulation tissue were observed in all samples. This is possibly due to the absence of the pulp and protective PRRS layer and/or to the altered chemical composition of the root dentine after root canal treatment. Furthermore, at the repair stage, formation of reparative bonelike tissue took place to a lesser extent in root filled teeth.
MNC Considerations in Identifying and Managing LGB Expatriate Stigmatization
Authors: Moeller Miriam , Maley Jane F. 
Published: January 2017

AbstractLesbian, gay and bisexual (LGB) expatriates are rightfully sceptical, and at times fearful, of international assignment experiences, owing to the sometimes hostile reception at assignment locations as a result of their sexual orientation. The authors argue that this hostility arises from a perceived incompatibility in values between the host country and LGB expatriates. Dissonance between the two value systems leaves LGB expatriates seemingly powerless to self‐manage imposed stigmas inside and outside the workplace at international assignment locations. The authors suggest that it is essential for the multinational corporation (MNC) to help manage these stigmas by implementing human resource management (HRM) practices and policies that recognize the needs of traditional and non‐traditional expatriates as substantially different. Using organizational legitimacy theory, the authors assert that MNCs’ strategic actions should entail a set of distinct practices and policies for LGB expatriates as a way to strive for acceptance within the LGB expatriate community and beyond. Managing value congruence in this manner ensures greater willingness of the LGB talent pool to undertake international career opportunities and is likely to result in better assignment experiences and outcomes. Outcomes of LGB stigmatization are discussed and suggestions are put forward on the MNC's role in supporting LGB expatriates and their families. Propositions relative to support are offered.
Pharmacists’ perceptions of pay for performance versus fee-for-service remuneration for the management of hypertension through pharmacist prescribing
Authors: Rosenthal Meagen M , Desai Nimisha , Houle Sherilyn K D 
Published: January 2017

Abstract

Objectives
As pharmacists expand their roles as patient care providers, remuneration must be offered for patient care activities apart from dispensing. Most jurisdictions paying for such services utilize the fee-for-service (FFS) model, while little is known about the role of pay for performance (P4P) within the pharmacy profession. This study aimed to elicit the experience of pharmacists practicing under both models within the Alberta Clinical Trial in Optimizing Hypertension (RxACTION) study in Alberta, Canada.

Methods
Pharmacist participants in RxACTION caring for at least one patient under FFS and under P4P were interviewed about their experiences until data saturation was reached. Interviews were conducted in June–July 2015, with responses audio recorded, transcribed and coded to identify key themes.

Key findings
Eight pharmacists were interviewed, with three key themes identified: a perceived comfort with the existing FFS model particularly due to its ease related to business planning, the transformative effect of the study on their practices and a preference for future models to consider a blend of both service count- and performance-driven metrics. The degree of influence pharmacists feel they can have on outcomes achieved by patients, the perceptions of patients and other healthcare professionals on outcome-based payment, and concerns with the impact of variable remuneration on the pharmacy business model are concerns raised with P4P in pharmacy practice.

Conclusions
This study reveals a hesitation to radically transform payment for pharmacists’ patient care services towards a P4P model. Efforts to implement P4P should therefore be gradual and accompanied with a robust evaluation plan.
Flexicurity between Europeanization and Varieties of Capitalism? A Comparative Analysis of Employment Protection Reforms in Portugal and Greece
Authors: Zartaloudis Sotirios , Kornelakis Andreas 
Published: January 2017

AbstractThe article examines the adoption of Flexicurity principles in Portugal and Greece during 2006–2009. Despite the similar conditions between the two cases and common EU stimulus, the process and final outcomes in the reform of their employment protection systems differed. In Portugal, the government persevered and implemented a reform in line with Flexicurity principles. By contrast, the Greek government initially favoured Flexicurity and initiated a reform process of the legal framework; however the reform was halted. The article explains this divergence by combining the insights of Europeanization and Varieties of Capitalism literatures. It is argued that in cases of Mixed Market Economies, ‘misfit’ with EU stimuli is a necessary, but not sufficient condition for institutional change. Instead, reforms depend on union structure and the existence of policy entrepreneurs favouring reform, which explains the divergent reform paths.
Mechanisms of metabolic memory and renal hypoxia as a therapeutic target in diabetic kidney disease
Authors: Hirakawa Yosuke , Tanaka Tetsuhiro , Nangaku Masaomi 
Published: January 2017

AbstractDiabetic kidney disease (DKD) is a worldwide public health problem. The definition of DKD is under discussion. Although the term DKD was originally defined as ‘kidney disease specific to diabetes,’ DKD frequently means chronic kidney disease with diabetes mellitus and includes not only classical diabetic nephropathy, but also kidney dysfunction as a result of nephrosclerosis and other causes. Metabolic memory plays a crucial role in the progression of various complications of diabetes, including DKD. The mechanisms of metabolic memory in DKD are supposed to include advanced glycation end‐products, deoxyribonucleic acid methylation, histone modifications and non‐coding ribonucleic acid including micro ribonucleic acid. Regardless of the presence of diabetes mellitus, the final common pathway in chronic kidney disease is chronic kidney hypoxia, which influences epigenetic processes, including deoxyribonucleic acid methylation, histone modification, and conformational changes in micro ribonucleic acid and chromatin. Therefore, hypoxia and oxidative stress are appropriate targets of therapies against DKD. Prolyl hydroxylase domain inhibitor enhances the defensive mechanisms against hypoxia. Bardoxolone methyl protects against oxidative stress, and can even reverse impaired renal function; a phase 2 trial with considerable attention to heart complications is currently ongoing in Japan.
Use of Play Therapy in Nursing Process: A Prospective Randomized Controlled Study
Authors: Sezici Emel , Ocakci Ayse Ferda , Kadioglu Hasibe 
Published: January 2017

AbstractPurposePlay therapy is a nursing intervention employed in multidisciplinary approaches to develop the social, emotional, and behavioral skills of children. In this study, we aim to determine the effects of play therapy on the social, emotional, and behavioral skills of pre‐school children through the nursing process.DesignA single‐blind, prospective, randomized controlled study was undertaken. The design, conduct, and reporting of this study adhere to the Consolidated Standards of Reporting Trials (CONSORT) guidelines.MethodsThe participants included 4‐ to 5‐year‐old kindergarten children with no oral or aural disabilities and parents who agreed to participate in the study. The Pre‐school Child and Family Identification Form and Social Competence and the Behavior Evaluation Scale were used to gather data. Games in the play therapy literature about nursing diagnoses (fear, social disturbance, impaired social interactions, ineffective coping, anxiety), which were determined after the preliminary test, constituted the application of the study.FindingsThere was no difference in the average scores of the children in the experimental and control groups in their Anger‐Aggression (AA), Social Competence (SC), and Anxiety‐Withdrawal (AW) scores beforehand (t = 0.015, p = .988; t = 0.084, p = .933; t = 0.214, p = .831, respectively). The difference between the average AA and SC scores in the post‐test (t = 2.041, p = .045; t = 2.692, p = .009, respectively), and the retests were statistically significant in AA and SC average scores in the experimental and control groups (t = 4.538, p = .000; t = 4.693; p = .000, respectively). In AW average scores, no statistical difference was found in the post‐test (t = 0.700, p = .486), whereas in the retest, a significant difference was identified (t = 5.839, p = .000).ConclusionsPlay therapy helped pre‐school children to improve their social, emotional, and behavioral skills. It also provided benefits for the children to decrease their fear and anxiety levels, to improve their communication and coping skills, and to increase their self‐esteem.Clinical RelevanceThe study concluded that play therapy helps develop the social, emotional, and behavioral skills of pre‐school children. It has also helped children lower their fear and anxiety levels, improve their communication and coping skills, and promote their self‐esteem. Pediatric nurses are recommended to include play therapy in their profession and in the nursing process.