bluuebunny/crossref_metadata_2025 huggingface dataset:
Virtual worlds to support patient group communication? A questionnaire study investigating potential for virtual world focus group use by respiratory patients
Authors: Taylor Michael J. , Taylor Dave , Vlaev Ivo , Elkin Sarah
Published: November 2015

Recent advances in communication technologies enable potential provision of remote education for patients using computer‐generated environments known as virtual worlds. Previous research has revealed highly variable levels of patient receptiveness to using information technologies for healthcare‐related purposes. This preliminary study involved implementing a questionnaire investigating attitudes and access to computer technologies of respiratory outpatients in order to assess potential for use of virtual worlds to facilitate health‐related education for this sample. Ninety‐four patients with a chronic respiratory condition completed surveys, which were distributed at a Chest Clinic. In accordance with our prediction, younger participants were more likely to be able to use and have access to a computer, and some patients were keen to explore use virtual worlds for healthcare‐related purposes: Of those with access to computer facilities, 14.50% expressed a willingness to attend a virtual world focus group. Results indicate that future virtual world health education facilities should be designed to cater to younger patients because this group is most likely to accept and use such facilities. Within the study sample, this is likely to comprise of people diagnosed with asthma. Future work could investigate the potential of creating a virtual world asthma education facility.
Pharmacological characterization of the opioid inactive isomers (+)‐naltrexone and (+)‐naloxone as antagonists of toll‐like receptor 4
Authors: Wang X , Zhang Y , Peng Y , Hutchinson M R , Rice K C , Yin H , Watkins L R
Published: November 2015

Background and Purpose

The toll‐like receptor TLR4 is involved in neuropathic pain and in drug reward and reinforcement. The opioid inactive isomers (+)‐naltrexone and (+)‐naloxone act as TLR4 antagonists, reversing neuropathic pain and reducing opioid and cocaine reward and reinforcement. However, how these agents modulate TLR4 signalling is not clear. Here, we have elucidated the molecular mechanism of (+)‐naltrexone and (+)‐naloxone on TLR4 signalling.

Experimental Approach

BV‐2 mouse microglial cell line, primary rat microglia and primary rat peritoneal macrophages were treated with LPS and TLR4 signalling inhibitors. Effects were measured using Western blotting, luciferase reporter assays, fluorescence microscopy and ELISA

Key Results

(+)‐Naltrexone and (+)‐naloxone were equi‐potent inhibitors of the LPS‐induced TLR4 downstream signalling and induction of the pro‐inflammatory factors NO and TNF‐α. Similarly, (+)‐naltrexone or (+)‐naloxone inhibited production of reactive oxygen species and increased microglial phagocytosis, induced by LPS. However, (+)‐naltrexone and (+)‐naloxone did not directly inhibit the increased production of IL‐1β, induced by LPS. The drug interaction of (+)‐naloxone and (+)‐naltrexone was additive. (+)‐Naltrexone or (+)‐naloxone inhibited LPS‐induced activation of IFN regulatory factor 3 and production of IFN‐β. However, they did not inhibit TLR4 signalling via the activation of either NF‐κB, p38 or JNK in these cellular models.

Conclusions and Implications

(+)‐Naltrexone and (+)‐naloxone were TRIF‐IFN regulatory factor 3 axis‐biased TLR4 antagonists. They blocked TLR4 downstream signalling leading to NO, TNF‐α and reactive oxygen species. This pattern may explain, at least in part, the in vivo therapeutic effects of (+)‐naltrexone and (+)‐naloxone.
Linking Executive Functions and Procedural Metacognition
Authors: Roebers Claudia M. , Feurer Emanuel
Published: November 2015

Traditionally, researchers have discussed executive function and metacognition independently. However, more recently, theoretical frameworks linking these two groups of higher order cognitive processes have been advanced. In this article, we explore the relationship between executive function and procedural metacognition, and summarize theoretical similarities. From a developmental perspective, the assumed theoretical resemblances seem to be supported, considering development trajectories and their substantial impact on areas that include learning and memory. Moreover, empirical evidence suggests direct relationships on the task level, on the level of latent variables, and in terms of involved brain regions. However, research linking the two concepts directly remains rare. We discuss evidence and developmental mechanisms, and propose ways researchers can investigate links between executive function and procedural metacognition.
Novel PORCN mutation in a severe case of Focal Dermal Hypoplasia
Authors: Ramirez‐Botero Andres Felipe , Eichler Sabrina , Rolfs Arndt , Pachajoa Harry
Published: November 2015

Focal dermal hypoplasia is a rare genetic disease characterized 8‐year‐old female who sought genetic counseling for multiple malformations, aggressive behavior and intellectual disability. Gene analysis confirmed focal dermal hypoplasia.
Construction Morphology and the Parallel Architecture of Grammar
Authors: Booij Geert , Audring Jenny
Published: November 2015

This article presents a systematic exposition of how the basic ideas of Construction Grammar (CxG) (Goldberg, ) and the Parallel Architecture (PA) of grammar (Jackendoff, ) provide the framework for a proper account of morphological phenomena, in particular word formation. This framework is referred to as Construction Morphology (CxM). As to the implications of CxM for the architecture of grammar, the article provides evidence against a split between lexicon and grammar, in line with CxG. In addition, it shows that the PA approach makes it possible to be explicit about what happens on which level of the grammar, and thus to give an insightful account of interface phenomena. These interface phenomena appear to require that various types of information are accessible simultaneously, and it is argued that constructional schemas have the right format for expressing these mutual dependencies between different types of information.
Analysis of the relationship between health status and mortality in hypercapnic patients with noninvasive ventilation
Authors: Oga Toru , Taniguchi Hiroyuki , Kita Hideo , Tsuboi Tomomasa , Tomii Keisuke , Ando Morihide , Kojima Eiji , Tomioka Hiromi , Taguchi Yoshio , Kaji Yusuke , Maekura Ryoji , Hiraga Toru , Sakai Naoki , Kimura Tomoki , Mishima Michiaki , Chin Kazuo
Published: November 2015

Background

Health status and mortality are important outcomes in patients with advanced pulmonary diseases receiving noninvasive ventilation (NIV). However, their relationship has not been thoroughly investigated.

Methods

The present study prospectively recruited 56 stable outpatients treated with NIV for chronic hypercapnic respiratory failure caused by chronic obstructive pulmonary disease and/or pulmonary tuberculosis sequelae. At baseline, health status was measured by the Medical Outcomes Study 36‐item short form, a generic questionnaire; the St. George's Respiratory Questionnaire (SGRQ), a respiratory‐specific questionnaire; and two respiratory failure‐specific questionnaires, the Maugeri Respiratory Failure questionnaire and the Severe Respiratory Insufficiency (SRI) questionnaire. Arterial blood gas, pulmonary function, dyspnea and psychological status were also measured.

Results

In cross‐sectional comparisons of the four health status questionnaires, the SGRQ and SRI questionnaire had lower floor and ceiling effects. During the 3‐year follow‐up, 16 patients (29%) died. Health status shown by the SGRQ and SRI was significantly predictive of mortality, independently of the physiological measures of low body mass index (BMI), hypercapnia, and low pulmonary function. Stepwise multivariate analyses indicated that the SRI summary score was the most significant predictor of mortality (P = 0.0006) followed by BMI (P = 0.012).

Conclusion

There was a significant relationship between health status and 3‐year mortality in patients with NIV, independently of under‐nutrition, hypercapnia and low pulmonary function. Health status measurement is important not only to comprehensively evaluate disease severity in relation to its close association with mortality, but also to elucidate factors that improve the survival of patients with advanced respiratory diseases.
Developing the Translational Research Workforce: A Pilot Study of Common Metrics for Evaluating the Clinical and Translational Award KL2 Program
Authors: Schneider Margaret , Guerrero Lourdes , Jones Lisa B. , Tong Greg , Ireland Christine , Dumbauld Jill , Rainwater Julie
Published: November 2015

Purpose

This pilot study describes the career development programs (i.e., NIH KL2 awards) across five Clinical and Translational Science Award (CTSA) institutions within the University of California (UC) system, and examines the feasibility of a set of common metrics for evaluating early outcomes.

Methods

A survey of program administrators provided data related to the institutional environment within which each KL2 program was implemented. Application and progress report data yielded a combined data set that characterized KL2 awardees, their initial productivity, and early career outcomes.

Results

The pilot project demonstrated the feasibility of aggregating common metrics data across multiple institutions. The data indicated that KL2 awardees were an accomplished set of investigators, both before and after the award period, representing a wide variety of disciplines. Awardees that had completed their trainee period overwhelmingly remained active in translational research conducted within an academic setting. Early indications also suggest high rates of success with obtaining research funding subsequent to the KL2 award.

Conclusion

This project offers a model for how to collect and analyze common metrics related to the education and training function of the CTSA Consortium. Next steps call for expanding participation to other CTSA sites outside of the University of California system.
Cochlear, auditory brainstem responses in Type 1 diabetes: relationship with metabolic variables and diabetic complications
Authors: Lasagni A. , Giordano P. , Lacilla M. , Raviolo A. , Trento M. , Camussi E. , Grassi G. , Charrier L. , Cavallo F. , Albera R. , Porta M. , Zanone M. M.
Published: November 2015

Aims

Few studies have analysed the presence of hearing abnormalities in diabetes. We assessed the presence of subclinical auditory alterations and their possible association with early vascular and neurological dysfunction in young adults with Type 1 diabetes of long duration.

Methods

Thirty‐one patients with Type 1 diabetes (mean age 33 ± 2.3 years, disease duration 25.7 ± 4.2 years) and 10 healthy controls underwent pure tone audiometry (PTA), distortion product otoacoustic emission (DPOAE) and auditory brainstem response (ABR) analyses. Associations with metabolic variables and chronic complications were explored.

Results

Compared with healthy controls, patients with diabetes had significantly higher mean hearing thresholds, although still within the normoacusic range. DPOAE intensities at medium frequencies (2.8–4 kHz) were significantly lower in patients with diabetes. In ABR, in addition to waves I, III and V, we observed the appearance of a visible wave IV in patients with diabetes compared with controls (prevalence 61% vs. 10%, P < 0.05), and its appearance was related to a prolonged I–V interval (4.40 ± 0.62 ms vs. 4.19 ± 0.58 ms, P < 0.05). Diastolic blood pressure was higher in people with abnormal DPOAE (P < 0.05), whereas systolic blood pressure correlated with wave V and interpeak I–V interval latencies. A trend towards an association between evidence of wave IV and the presence of somatic neuropathy or abnormal cardiovascular autonomic tests was observed.

Conclusions

Young adults with long‐term Type 1 diabetes have subclinical abnormalities in qualitative auditory perception, despite normal hearing thresholds, which might reflect neuropathic and/or vascular alterations.
Organic cation transporter 1 variants and gastrointestinal side effects of metformin in patients with Type 2 diabetes
Authors: Dujic T. , Causevic A. , Bego T. , Malenica M. , Velija‐Asimi Z. , Pearson E. R. , Semiz S.
Published: November 2015

Aims

Metformin is the most widely used oral anti‐diabetes agent and has considerable benefits over other therapies, yet 20–30% of people develop gastrointestinal side effects, and 5% are unable to tolerate metformin due to the severity of these side effects. The mechanism for gastrointestinal side effects and their considerable inter‐individual variability is unclear. We have recently shown the association between organic cation transporter 1 (OCT1) variants and severe intolerance to metformin in people with Type 2 diabetes. The aim of this study was to explore the association of OCT1 reduced‐function polymorphisms with common metformin‐induced gastrointestinal side effects in Type 2 diabetes.

Methods

This prospective observational cohort study included 92 patients with newly diagnosed Type 2 diabetes, incident users of metformin. Patients were genotyped for two common loss‐of‐function variants in the OCT1 gene (SLC22A1): R61C (rs12208357) and M420del (rs72552763). The association of OCT1 reduced‐function alleles with gastrointestinal side effects was analysed using logistic regression.

Results

Forty‐three patients (47%) experienced gastrointestinal adverse effects in the first 6 months of metformin treatment. Interestingly, the number of OCT1 reduced‐function alleles was significantly associated with over two‐fold higher odds of the common metformin‐induced gastrointestinal side effects (odds ratio = 2.31, 95% confidence interval 1.07–5.01, P = 0.034).

Conclusions

In conclusion, we showed for the first time the association between OCT1 variants and common metformin‐induced gastrointestinal side effects. These results confirm recent findings related to the role of OCT1 in severe metformin intolerance, and suggest that high inter‐individual variability in mild/moderate and severe gastrointestinal intolerance share a common underlying mechanism. These data could contribute to more personalized and safer metformin treatment.
Extrinsic Esophageal Compression by Cervical Osteophytes in Diffuse Idiopathic Skeletal Hyperostosis: A Contraindication to Transesophageal Echocardiography?
Authors: Chang Kevin , Barghash Maya , Donnino Robert , Freedberg Robin S. , Hagiwara Mari , Bennett Genevieve , Benenstein Ricardo , Saric Muhamed
Published: November 2015

Contraindications to transesophageal echocardiography (TEE) include various esophageal pathologies, but compression of the esophagus by vertebral osteophytes is not listed in the current American Society of Echocardiography guidelines. We report a case of diffuse idiopathic skeletal hyperostosis (DISH) in an 81‐year‐old man who had incidentally been found to have extrinsic esophageal compression by cervical osteophytes prior to a proposed TEE. The incidence of esophageal perforation in patients with DISH and vertebral osteophytes is not well documented. We believe these patients are at increased risk of esophageal perforation during TEE, and thus, TEE may be relatively contraindicated in patients with DISH.
Coronary Flow Reserve Predicts Longitudinal Myocardial Deformation Capacity in Heart‐Transplanted Patients
Authors: Clemmensen Tor Skibsted , Løgstrup Brian Bridal , Eiskjær Hans , Poulsen Steen Hvitfeldt
Published: November 2015

Aims

This study aimed to evaluate the role of microvascular dysfunction on left ventricular (LV) longitudinal deformation, filling pressures, and exercise capacity in heart‐transplanted (HTx) patients.

Methods and Results

Fifty‐seven HTx patients underwent comprehensive echocardiographic graft function assessment during symptom‐limited, semisupine exercise test with simultaneous right heart catheterization. Coronary flow velocity reserve (CFVR) was measured in the left anterior descending artery using pulsed Doppler echocardiography. We divided patients into two groups based on upper and lower median of CFVR. Twenty‐six healthy subjects served as controls. Compared with healthy controls, HTx patients had reduced CFVR (P < 0.0001), exercise capacity (P < 0.0001), and LV longitudinal deformation capacity (P < 0.0001). HTx patients in the reduced CFVR group (CFVR < 2.73) were more symptomatic (P < 0.0001) and had higher prevalence of coronary cardiac allograft vasculopathy (CAV) (P < 0.0001) than patients in the high CFVR group. Systolic function improved in both HTx groups during exercise. However, LV longitudinal myocardial deformation improved significantly more in the high CFVR group (P < 0.0001). Peak exercise LV global longitudinal strain and CFVR were strongly correlated (r = 0.8, P < 0.0001). A weak correlation was observed between CFVR and invasive cardiac index at peak exercise (r = 0.35, P < 0.01) and CFVR and LV filling measured by E/e′ ratio (r = −0.41, P < 0.01) and pulmonary capillary wedge pressure (r = −0.30, P < 0.05).

Conclusion

HTx patients have reduced CFVR, exercise capacity, and LV longitudinal myocardial deformation capacity compared with healthy individuals. HTx patients with reduced CFVR are more symptomatic and have increased prevalence of CAV. Furthermore, reduced CFVR is correlated with reduced LV longitudinal myocardial deformation and exercise capacity.
INFORMAL SECTOR AND ECONOMIC DEVELOPMENT: THE CREDIT SUPPLY CHANNEL
Authors: Massenot Baptiste , Straub Stéphane
Published: November 2015

The standard view suggests that removing barriers to entry and improving judicial enforcement reduces informality and boosts investment and growth. However, a general equilibrium approach shows that this conclusion may hold to a lesser extent in countries with a constrained supply of funds because of, for example, a more concentrated banking sector or lower financial openness. When the formal sector grows larger in those countries, more entrepreneurs become creditworthy, but the higher pressure on the credit market limits further capital accumulation. We show empirical evidence consistent with these predictions. (JEL O16, O43, E26)
Nociceptin/orphanin FQ up‐regulates P2X3 receptors in primary cultures of neonatal rat trigeminal ganglion neurons
Authors: Wang Yan , Long Hu , Jian Fan , Li Xiaoyu , Yang Xin , Zhao Zhihe , Lai Wenli
Published: November 2015

Recent evidence indicates a nociceptive role of the nociceptin/orphanin FQ–opioid receptor‐like receptor (N/OFQ‐ORL1) system in craniofacial pain; however, the mechanisms of such an effect remain unclear. We investigated whether the action of N/OFQ involves the modulation of P2X3, a pain‐transducing ionotropic receptor. Double‐labeled immunohistochemical staining was used to determine the co‐localization of ORL1 and P2X3 receptors in the trigeminal ganglia (TG) of neonatal Sprague‐Dawley rats. The effect of N/OFQ (at a concentration ranging from 1 pM to 10 nM) on the expression of P2X3 receptors was detected by RT‐PCR, western blotting, and immunocytochemical staining. We found that ORL1 receptors were co‐localized with P2X3 receptors and that the application of N/OFQ could up‐regulate, in a concentration‐dependent manner, the expression of P2X3 receptor mRNA and P2X3 receptor protein in TG neurons. Immunocytochemical staining also revealed enhanced P2X3 immunoreactivity beneath the neuronal membrane and an increased percentage of P2X3‐positive neurons after treatment with N/OFQ. Those effects were completely blocked by a specific ORL1 antagonist, UFP‐101. Our results suggest that the activation of ORL1 receptors by N/OFQ can potentiate P2X3 receptors in primary cultures of neonatal trigeminal neurons, which may be a mechanism for the nociceptive role of N/OFQ in the modulation of craniofacial pain. Our findings may also have implications in treating craniofacial pain.
A common garden design reveals population‐specific variability in potential impacts of hybridization between populations of farmed and wild Atlantic salmon, Salmo salar L.
Authors: Harvey Alison C. , Glover Kevin A. , Taylor Martin I. , Creer Simon , Carvalho Gary R.
Published: November 2015

Released individuals can have negative impacts on native populations through various mechanisms, including competition, disease transfer and introduction of maladapted gene complexes. Previous studies indicate that the level of farmed Atlantic salmon introgression in native populations is population specific. However, few studies have explored the potential role of population diversity or river characteristics, such as temperature, on the consequences of hybridization. We compared freshwater growth of multiple families derived from two farmed, five wild and two F1 hybrid salmon populations at three contrasting temperatures (7°C, 12°C and 16°C) in a common garden experiment. As expected, farmed salmon outgrew wild salmon at all temperatures, with hybrids displaying intermediate growth. However, differences in growth were population specific and some wild populations performed better than others relative to the hybrid and farmed populations at certain temperatures. Therefore, the competitive balance between farmed and wild salmon may depend both on the thermal profile of the river and on the genetic characteristics of the respective farmed and wild strains. While limited to F1 hybridization, this study shows the merits in adopting a more complex spatially resolved approach to risk management of local populations.
Upstream migration of amphidromous gobies of La Réunion Island: implication for management
Authors: Lagarde R. , Teichert N. , Boussarie G. , Grondin H. , Valade P.
Published: November 2015

Diadromous species of tropical islands face numerous anthropogenic disturbances. Understanding how these disturbances affect the population dynamic of these species is important to develop ecologically based management measures. The upstream migration dynamics of two amphidromous gobies, Sicyopterus lagocephalus (Pallas) and Cotylopus acutipinnis (Guichenot), was described using intensive fishway monitoring (28 sampling dates over 1.5 years, 13 000 S. lagocephalus, 23 000 C. acutipinnis captured). Migration peak occurred for both species during the afternoon at the end of austral winter/beginning of austral summer. Abundance and size of fish caught in the river showed a marked impact of a dam (six sampling dates approximately 4000 individuals of each species captured). This study provides critical data for better management of fishways used by tropical amphidromous gobies. It appears especially important to reduce unwanted rheotactic sources that attract the fish away from the fishway's entrance.
Home medicines reviews in Australian war veterans taking warfarin do not influence international normalised ratio control
Authors: Bereznicki L. R. E. , van Tienen E. C. , Stafford A.
Published: November 2015

Background

The clinical outcomes of warfarin are largely dependent on the international normalised ratio (INR) control achieved, and strategies to improve the time in therapeutic range (TTR) should be identified and widely implemented in practice.

Aims

To investigate the influence of pharmacist‐led medication reviews on INR control and observe the quality of INR control in Australian veterans who take warfarin.

Methods

We undertook a retrospective cohort study using administrative claims data for Australian veterans and war‐widows identified by the Department of Veterans’ Affairs who were regularly dispensed warfarin and invited them to contact the research team. Pathology providers were subsequently contacted to provide INR results.

Results

INR data were available for 344 of 818 (42.1%) veterans who consented to participate in the study; 64.4% were male and the median age was 83 years. The overall TTR for the veteran cohort during the study period was 64.0%. There was no difference in the TTR in the 6 months following home medicines review (HMR) compared with the control group (63.0% vs 67.0%, P = 0.27), with the TTR in patients with INR data available in the 6 months prior to, and the 6 months following HMR, remaining high (67.9% vs 69.6% P = 0.63). Approximately, one‐third of veterans in this study had a percentage TTR below 60%.

Conclusions

INR was well‐controlled in this elderly cohort, comparable to that achieved in recent randomised trials involving warfarin. Pharmacist‐led medication reviews were not associated with a change in INR control.
Des indicateurs «SMART» pour mesurer le travail décent: proposition dans la perspective du programme de développement pour l'après‐2015
Authors: OSTERMEIER Martin , LINDE Sarah , LAY Jann , PREDIGER Sebastian
Published: November 2015

Les indicateurs associés aux objectifs du Millénaire pour le développement présentent plusieurs lacunes: des problèmes de mesure et d'interprétation, l'utilisation de données agrégées et des hypothèses inadaptées aux pays en développement. Les auteurs proposent par conséquent quatre nouveaux indicateurs de l'emploi productif et du travail décent: l'augmentation de la part du travail dans la valeur ajoutée par těte, le taux de travailleurs pauvres et la proportion de travailleurs qui perçoivent un revenu inférieur à un minimum donné, fixé en valeur absolue d'abord puis à 60 pour cent du revenu du travail médian. Deux cas d'espèce – Ouganda et Pérou – illustrent l'application pratique de ces indicateurs.
Out of the shadows: Classifying economies by the extent and nature of employment in the informal economy
Authors: WILLIAMS Colin C.
Published: November 2015

Given the prevalence of informality, this article proposes a typology for classifying countries by the extent and nature of employment in the informal economy, rather than by the composition of their formal economies. The author analyses ILO data on employment in the informal economy in 36 developing countries, and shows that there is a significant correlation between cross‐national variations in the degree and intensity of informalization and cross‐national variations in social and economic indicators such as levels of GNP per capita, corruption, poverty, taxation and social contributions. The article concludes by discussing implications for theory and policy.
Synthesis of ZrB2 Powders from ZrO2, BN, and C
Authors: Yan Chunlei , Liu Rongjun , Zhang Changrui , Cao Yingbin , Long Xianhai
Published: November 2015

Submicrometer (200–800 nm) ZrB2 powders have been successfully prepared via a new ZrO2–C–BN precursor powder system at a relatively low temperature (1550°C) for 1.5 h. As a moderate cost boron source, BN has a well‐defined stoichiometry and low impurity. Both thermodynamic and experimental results indicated that ZrC was formed below 1300°C, a temperature required for ZrB2 formation. Moreover, the reaction of ZrC–BN mixture at 1300°C indicated that the ZrC acted as an effective direct reducing reagent for BN to form ZrB2, indicating that the pathway involving the formation of intermediate phase ZrC determined the formation mechanism.
Elevated Temperature Strength Enhancement of ZrB2–30 vol% SiC Ceramics by Postsintering Thermal Annealing
Authors: Neuman Eric W. , Hilmas Gregory E. , Fahrenholtz William G.
Published: November 2015

The mechanical properties of dense, hot‐pressed ZrB2–30 vol% SiC ceramics were characterized from room temperature up to 1600°C in air. Specimens were tested as hot‐pressed or after hot‐pressing followed by heat treatment at 1400°C, 1500°C, 1600°C, or 1800°C for 10 h. Annealing at 1400°C resulted in the largest increases in flexure strengths at the highest test temperatures, with strengths of 470 MPa at 1400°C, 385 MPa at 1500°C, and 425 MPa at 1600°C, corresponding to increases of 7%, 8%, and 12% compared to as hot‐pressed ZrB2–SiC tested at the same temperatures. Thermal treatment at 1500°C resulted in the largest increase in elastic modulus, with values of 270 GPa at 1400°C, 240 GPa at 1500°C, and 120 GPa at 1600°C, which were increases of 6%, 12%, and 18% compared to as hot‐pressed ZrB2–SiC. Neither ZrB2 grain size nor SiC cluster size changed for these heat‐treatment temperatures. Microstructural analysis suggested additional phases may have formed during heat treatment and/or dislocation density may have changed. This study demonstrated that thermal annealing may be a useful method for improving the elevated temperature mechanical properties of ZrB2‐based ceramics.
Transformational and abusive leadership practices: impacts on novice nurses, quality of care and intention to leave
Authors: Lavoie‐Tremblay Mélanie , Fernet Claude , Lavigne Geneviève L. , Austin Stéphanie
Published: November 2015

Aims

To investigate the impact of nurse managers exercising transformational vs. abusive leadership practices with novice nurses.

Background

In a nursing shortage context, it is important to understand better the factors that potentially influence the retention of nurses in the early stages of their career. A large body of research has found that transformational leadership practices have a positive influence on employee functioning. However, very little research exists about the detrimental impact of abusive leadership practices, much less in a nursing context.

Design

A cross‐sectional design where 541 nurses from the province of Quebec (Canada) were questioned in the fall of 2013.

Methods

A self‐administered questionnaire was completed by nurses with less than five years of nursing experience.

Results

Results from three linear regression analysis indicated that transformational leadership practices potentially lead to high quality care and weak intention to quit the healthcare facilities. Conversely, abusive leadership practices potentially lead to poorer quality care and to strong intention to quit the healthcare facilities and the nursing profession.

Conclusion

Paying close attention to the leadership practices of nurse managers could prove effective in improving patient care and increasing the retention of new nurses, which is helpful in resolving the nursing shortage. Our results specifically suggest not only that we promote supportive leadership practices (transformational leadership) but, most of all, that we spread the word that abusive leadership creates working conditions that could be detrimental to the practice of nursing at career start.
Health Care Matters: Supply Chains In and Of the Health Sector
Authors: Abdulsalam Yousef , Gopalakrishnan Mohan , Maltz Arnold , Schneller Eugene
Published: November 2015

Providing health care involves a complex enterprise, and the trade‐off between quality and cost has been particularly stark compared to other industries. However, a recent focus on health sector supply networks is now producing significant innovations and improvements. This Special Topic Forum illustrates for the academic and practitioner community how health care supply chain research can benefit from our evolving understanding of supply chains and help push that understanding even further. We classify health care supply chain research into two broad categories—supply chain in health care and supply chain of health care—to set an agenda for future research.
Evidence of gene orthology and trans‐species polymorphism, but not of parallel evolution, despite high levels of concerted evolution in the major histocompatibility complex of flamingo species
Authors: Gillingham M. A. F. , Courtiol A. , Teixeira M. , Galan M. , Bechet A. , Cezilly F.
Published: November 2015

The major histocompatibility complex (MHC) is a cornerstone in the study of adaptive genetic diversity. Intriguingly, highly polymorphic MHC sequences are often not more similar within species than between closely related species. Divergent selection of gene duplicates, balancing selection maintaining trans‐species polymorphism (TSP) that predate speciation and parallel evolution of species sharing similar selection pressures can all lead to higher sequence similarity between species. In contrast, high rates of concerted evolution increase sequence similarity of duplicated loci within species. Assessing these evolutionary models remains difficult as relatedness and ecological similarities are often confounded. As sympatric species of flamingos are more distantly related than allopatric species, flamingos represent an ideal model to disentangle these evolutionary models. We characterized MHC Class I exon 3, Class IIB exon 2 and exon 3 of the six extant flamingo species. We found up to six MHC Class I loci and two MHC Class IIB loci. As all six species shared the same number of MHC Class IIB loci, duplication appears to predate flamingo speciation. However, the high rate of concerted evolution has prevented the divergence of duplicated loci. We found high sequence similarity between all species regardless of codon position. The latter is consistent with balancing selection maintaining TSP, as under this mechanism amino acid sites under pathogen‐mediated selection should be characterized by fewer synonymous codons (due to their common ancestry) than under parallel evolution. Overall, balancing selection maintaining TSP appears to result in high MHC similarity between species regardless of species relatedness and geographical distribution.
Expression of class II histone deacetylases in two mouse models of temporal lobe epilepsy
Authors: Jagirdar Rohan , Drexel Meinrad , Bukovac Anneliese , Tasan Ramon O. , Sperk Günther
Published: November 2015

Epigenetic mechanisms like altered histone acetylation may have a crucial role in epileptogenesis. In two mouse models of temporal lobe epilepsy, we investigated changes in the expression of class II histone deacetylases (HDAC), a group of signal transducers that shuttle between nucleus and cytoplasm. Intrahippocampal injection of kainic acid (KA) induced a status epilepticus, development of spontaneous seizures (after 3 days), and finally chronic epilepsy and granule cell dispersion. Expression of class II HDAC mRNAs was investigated at different time intervals after KA injection in the granule cell layers and in sectors CA1 and CA3 contralateral to the site of KA injection lacking neurodegeneration. Increased expression of HDAC5 and 9 mRNAs coincided with pronounced granule cell dispersion in the KA‐injected hippocampus at late intervals (14–28 days after KA) and equally affected both HDAC9 splice variants. In contrast, in the pilocarpine model (showing no granule cell dispersion), we observed decreases in the expression of HDAC5 and 9 at the same time intervals. Beyond this, striking similarities between both temporal lobe epilepsy models such as fast decreases in HDAC7 and 10 mRNAs during the acute status epilepticus were observed, notably also in the contralateral hippocampus not affected by neurodegeneration. The particular patterns of HDAC mRNA expression suggest a role in epileptogenesis and granule cell dispersion. Reduced expression of HDACs may result in increased expression of pro‐ and anticonvulsive proteins. On the other hand, export of HDACs from the nucleus into the cytoplasm could allow for deacetylation of cytoplasmatic proteins involved in axonal and dendritic remodeling, like granule cell dispersion.

image

HDAC 5 and HDAC 9 expression is highly increased in granule cells of the KA‐injected hippocampus and parallels granule cell dispersion. Both HDACs are thought to be targeted to the cytoplasm and to act there by deacetylating cytoplasmatic (e.g. cytosceleton‐related) proteins.
Liver injury from nonsteroidal anti‐inflammatory drugs in the United States
Authors: Schmeltzer Paul A. , Kosinski Andrzej S. , Kleiner David E. , Hoofnagle Jay H. , Stolz Andrew , Fontana Robert J. , Russo Mark W. ,   the Drug‐Induced Liver Injury Network (DILIN)
Published: November 2015

Background & Aims

Nonsteroidal anti‐inflammatory drugs (NSAIDs) are commonly used and have been associated with hepatotoxicity. Studies of liver injury from NSAIDs have been retrospective and prospective data are lacking. The aim was to report the features and outcomes of the subjects with severe drug‐induced liver injury from NSAIDS.

Methods

The U.S. Drug Induced Liver Injury Network is a prospective registry of idiosyncratic drug hepatotoxicity. All patients are evaluated in a standard fashion and followed up for at least 6 months.

Results

Of 1221 Drug Induced Liver Injury Network cases that were adjudicated, 30 cases were attributed to eight different NSAIDs. The mean age was 52 years old, 24 (80%) were women, and 21 (70%) were Caucasian. The mean latency was 67 days. Common signs and symptoms at presentation were nausea (73%), jaundice (67%) and dark urine (67%). Mean peak serum aspartate aminotransferase, alanine aminotransferase, total bilirubin and alkaline phosphatase were 898 U/L, 1060 U/L, 12.2 mg/dl and 326 U/L. The most common pattern of injury was hepatocellular (70%) and autoantibodies were detected in 33% of cases. Diclofenac, was the most frequently implicated NSAID (16/30 cases), and characterized by hepatocellular injury. Seventeen cases resulted in hospitalization or prolongation of hospitalization and one patient died from complications of Stevens–Johnson syndrome because of diclofenac.

Conclusions

Hepatocellular injury is the most common pattern seen with NSAID hepatotoxicity, and diclofenac is the most frequently implicated agent. Given the number of NSAID alternatives, diclofenac should be reserved for patients who fail other NSAIDs and a high level of suspicion for hepatotoxicity should be maintained.
Lack of endogenous cholecystokinin promotes cholelithogenesis in mice
Authors: Wang H. H. , Liu M. , Portincasa P. , Tso P. , Wang D. Q.‐H.
Published: November 2015

Background

Celiac disease is an autoimmune enteropathy caused by a permanent intolerance to dietary gluten in genetically predisposed individuals. Cholecystokinin (CCK) release from the proximal small intestine and gallbladder emptying in response to a fatty meal are greatly reduced in celiac patients before they start the gluten‐free diet, showing a genetic predisposition to gallstones.

Methods

To elucidate the complex pathophysiological mechanisms determining the biliary characteristic of celiac disease, we investigated the effect of the absence of endogenous CCK on cholesterol crystallization and gallstone formation in mice fed a lithogenic diet for 28 days.

Key Results

Fasting gallbladder volumes were increased and the response of gallbladder emptying to the high‐fat diet was impaired in CCK knockout (KO) mice compared to wild‐type mice. Because of the absence of CCK, small intestinal transit time was prolonged and intestinal cholesterol absorption was increased. During 28 days of feeding, elevated biliary cholesterol concentrations and gallbladder stasis promoted the growth and agglomeration of solid cholesterol crystals into microlithiasis and stones. Thus, cholesterol crystallization and gallstone formation were accelerated in CCK KO mice. In contrast, daily intraperitoneal administration of CCK‐8 reduced gallstone formation in CCK KO mice even on the lithogenic diet.

Conclusions & Inferences

The lack of endogenous CCK enhances susceptibility to gallstones by impairing gallbladder contractile function and small intestinal motility function. These findings show that celiac disease is an important risk factor for gallstone formation and the gallbladder motility function should be routinely examined by ultrasonography and gallbladder stasis should be prevented in celiac patients.
Targeting the lysosome in cancer
Authors: Piao Shengfu , Amaravadi Ravi K.
Published: November 2015

Lysosomes are membrane‐bound intracellular organelles that receive macromolecules delivered by endocytosis, phagocytosis, and autophagy for degradation and recycling. Over the last decade, advances in lysosome research have established a broad role for the lysosome in the pathophysiology of disease. In this review, we highlight the recent discoveries in lysosome biology, with an emphasis on their implications for cancer therapy. We focus on targeting the lysosome in cancer by exploring lysosomal biogenesis and its role in the crosstalk between apoptosis and autophagy. We also discuss how lysosomal inhibition could emerge as a new therapeutic strategy to overcome drug resistance in cancer.
Is YouTube useful as a source of information for Sjögren's syndrome?
Authors: Delli K , Livas C , Vissink A , Spijkervet FKL
Published: November 2015

Objectives

To quantitatively and qualitatively assess the characteristics of YouTube videos dealing with Sjögren's syndrome.

Materials & Methods

A comprehensive electronic search was performed for ‘Sjögren's syndrome' in YouTube. After excluding duplicates, irrelevant videos, and non‐English‐language domains, 70 videos were included for analysis. Videos were classified as useful, misleading, or personal experience. The overall quality of videos was scored according to the Global Quality Scale (GQS). Useful videos were assessed for reliability and comprehensiveness based on two 5‐point scales. Key points of the misleading videos were explored and patients' personal experiences were further investigated.

Results

Thirty‐six videos (51.4%) were classified as useful, 6 (8.6%) as misleading, and 28 (40%) as patient's personal experience. Independent users tend to upload videos with personal experience, while university channels/professional organizations share useful videos with evidence‐based information. Significant difference was observed in GQS among useful, misleading videos, and patient's experiences. The mean reliability, comprehensiveness, and GQS scores of useful videos were 2.5 (s.d.:1.2), 2.6 (s.d.:1.4), and 3.4 (s.d.:1.0), respectively, whereas only six videos (16.7%) were rated as complete vis‐à‐vis content. The most frequently misleading topics were etiology and treatment.

Conclusions

Specialists should refer their patients to validated e‐information resources and actively participate in the development of video‐sharing platforms.
Skeletal adaptations and phylogeny of the oldest mole Eotalpa (Talpidae, Lipotyphla, Mammalia) from the UK Eocene: the beginning of fossoriality in moles
Authors: Hooker Jerry J.
Published: November 2015

The oldest talpid, Eotalpa, was previously known only from isolated cheek teeth from the European late Middle Eocene to earliest Oligocene. Screenwashing of Late Eocene sediments of the Hampshire Basin, UK, has yielded cranial and postcranial elements: maxilla, dentary, ulna, metacarpals, distal tibia, astragalus, calcaneum, metatarsals and phalanges. In addition to M1–2 myotodonty, typical talpid features are as follows: ulna with long medially curved olecranon and deep abductor fossa and astragalar body with lateral process. However, Eotalpa retains certain soricid‐like primitive states (M1 preparacrista, P4 with prominent mesiolingual protocone lobe, strongly angled astragalar neck and calcaneum with no space for a cuboid medial process) not found in modern talpids. Eotalpa is more derived than the most primitive living talpid Uropsilus in having lost the M1–2 talon shelf, developed a convex radial facet on the ulna, an incipient proximal olecranon crest, relatively shorter metapodials and depressed manual unguals. Its astragalus with medial trochlear ridge taller than the lateral one and massive medial plantar process is typical of the Lipotyphla. Eotalpa lacks synostosis of tibia and fibula, found in other Talpidae, Soricidae and Erinaceidae, suggesting that synostosis in these groups has been independently acquired. Cladistic analysis places Eotalpa as stem member of the Talpidae and shows that much homoplasy arose during the early evolution of the family. Ground dwelling in Eotalpa is indicated by the following: astragalus with a medially dipping head, curved in a single plane; calcaneum with distal peroneal process and strongly overlapping ectal and sustentacular facets; and matching sized ectal and sustentacular facets on calcaneum and astragalus. These features would have restricted ankle mobility. Ungual and metatarsal shape and ulnar structure suggest a primitive stage in fossorial evolution and argue against a semiaquatic precursor stage in talpid fossoriality. Shrew‐moles may represent a reversal to surface foraging rather than an intermediate stage in fossoriality.
Coblation of Femoral and Sciatic Nerve for Stump Pain and Phantom Limb Pain: A Case Report
Authors: Zeng Yuanjie , Wang Xiaoping , Guo Yuna , He Liangliang , Ni Jiaxiang
Published: November 2015

Background

There is currently no reliable treatment for stump pain and phantom limb pain. Peripheral factors play a significant role in the pathophysiology of stump pain and phantom limb pain. Coblation technology is a relatively new technology that has shown promise in treating neuropathic pain.

Case Report

This report describes the use of coblation technology on femoral and sciatic nerve for stump pain and phantom limb pain. An ultrasound‐guided perineural infiltration anesthesia surrounding the neuroma was first performed and achieved approximately 60% stump pain relief that lasted for 2 hours, but no relief of the phantom limb pain. An ultrasound‐guided femoral and sciatic nerve block was performed to obtain longer pain relief. The patient reported approximately 80% pain relief in both stump pain and phantom limb pain that lasted for 40 hours. This finding suggested other factors in addition to the ultrasound‐detected neuroma in the residual limb generating pain for this patient. Coblation of femoral and sciatic nerves was performed. The stump pain was completely relieved immediately after operation. At 1, 3, and 6 months postoperative review, 80% relief of both stump and phantom limb pain was achieved. Overall activity was improved and there was no need for pain medications. The analgesic effect was stable during the 6‐month follow‐up period.

Conclusion

Our report suggests that coblation technology may be useful treatment for stump pain and phantom limb pain. Treatments focusing on peripheral nerves may be more effective than those focusing on the neuroma. This finding needs additional study for confirmation.
IgG4‐related disease manifesting the gastric wall thickening
Authors: Kawano Hiroo , Ishii Aya , Kimura Tokuhiro , Takahashi Tsuyoshi , Hironaka Hideharu , Kawano Michitaka , Yamaguchi Michiya , Oishi Keiji , Kubo Makoto , Matsui Shoko , Notohara Kenji , Ikeda Eiji
Published: November 2015

IgG4‐related disease (IgG4‐RD) is a recently designated disease entity and its full picture has not yet been elucidated. Here, we report an unusual case of a patient with gastric wall thickening secondary to IgG4‐RD. A 68‐year‐old male visited our hospital with itchy skin lesions and an episode of organizing pneumonia. On the suspicion of malignancy‐associated skin lesions, computed tomography (CT) was performed. The CT revealed prominent thickening of the gastric wall. Due to the possibility of malignancy, the patient underwent distal gastrectomy. Histopathological examination showed fibrosis of the submucosa and prominent thickening of the muscularis propria. Most of infiltrating cells were IgG4‐positive plasma cells. Post‐operative blood test revealed significantly high serum levels of total IgG and IgG4. Based on these histological features, the patient was given a definitive diagnosis of IgG4‐RD. Further accumulation of cases like the present case that develop IgG4‐RD with rare manifestations would lead to the elucidation of pathogenesis.