bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of ICT on learning on-the-job
Authors: Hortovanyi Lilla , Ferincz Adrienn
Published: January 2015

Purpose

– The purpose of this paper is to analyse the relationship between on-the-job learning and information and communication technology (ICT).

Design/methodology/approach

– Action research methodology was applied to study 62 small- and medium-sized corporations, and to interview over 200 knowledge workers and managers. The qualitative, textual data collected were transformed into 16 variables and analysed by multidimensional scaling.

Findings

– The paper provides insights into the optimal use of ICT in intra-organizational knowledge transfer and learning. We found that it is essential to use the right combination and number of technologies, aligned with the organization’s internal processes. Four different types of organizations with sub-optimal usage of ICT and possible strategies for them to reach the optimal zone were identified. For successful organizational learning, however, more is needed: the individual must also understand the value of learning and must be motivated to take part in it.

Research limitations/implications

– On-the-job-learning can be facilitated with ICT tools but only if the organization invests in the right levels of ICT. Too much technology can be as destructive to on-the-job learning as too little. Future research should look at other contexts (size, age, industry, etc.) to validate these findings.

Practical implications

– The paper demonstrates the effective use of ICT in knowledge transfer and on-the-job learning.

Originality/value

– The paper extends our understanding of human–computer collaboration. It highlights that finding the optimal level of ICT is essential for successful knowledge transfer and on-the-job learning.
Epistemological beliefs and knowledge sharing in work teams
Authors: Weinberg Frankie J.
Published: January 2015

Purpose

– The purpose of this paper is to present a knowledge-sharing model that explains individual members’ motivation to share knowledge (knowledge donation and knowledge collection).

Design/methodology/approach

– The model is based on social-constructivist theories of epistemological beliefs, learning and distributed cognition, and is organized via the mechanism of propositional control, which suggests that attitudes or beliefs largely drive one’s behaviors. This paper also explores how epistemological belief systems may influence behavior processes at work.

Findings

– The model presented consists of five epistemological belief dimensions consistent with previous theorization about personal epistemologies. This paper demonstrates how sophisticated (as opposed to naive) beliefs on each of these five dimensions can stimulate one’s intrinsic desire to engage in knowledge-sharing behaviors.

Research limitations/implications

– The model is constrained by the assumptions that learning takes place socially and within a specific context (in this case, the team setting), and that a great deal of knowledge sharing is preferred over little knowledge sharing. This paper adds to the understanding of workplace learning by establishing a possible new antecedent to explain the process of how team members are motivated to engage in knowledge-sharing behaviors.

Practical implications

– The model may be used for knowledge management and to understand ineffectiveness in teams. It also may assist in human resource functions including selecting and training team members for knowledge-intensive positions.

Social implications

– Epistemology affects collaborative relationships. Collaborations and associated knowledge-sharing behaviors among work team members who design and implement products for public use are imperative toward developing products free from health and safety issues.

Originality/value

– This paper provides a model for understanding and developing motivation to engage in individual knowledge-sharing behaviors among work team members, which is considered critical toward an organization’s competitive advantage.
Treatment intensity and childhood apraxia of speech
Authors: Namasivayam Aravind K. , Pukonen Margit , Goshulak Debra , Hard Jennifer , Rudzicz Frank , Rietveld Toni , Maassen Ben , Kroll Robert , van Lieshout Pascal
Published: January 2015

Background

Intensive treatment has been repeatedly recommended for the treatment of speech deficits in childhood apraxia of speech (CAS). However, differences in treatment outcomes as a function of treatment intensity have not been systematically studied in this population.

Aim

To investigate the effects of treatment intensity on outcome measures related to articulation, functional communication and speech intelligibility for children with CAS undergoing individual motor speech intervention.

Methods & Procedures

A total of 37 children (32–54 months of age) with CAS received 1×/week (lower intensity) or 2×/week (higher intensity) individual motor speech treatment for 10 weeks. Assessments were carried out before and after a 10‐week treatment block to study the effects of variations in treatment intensity on the outcome measures.

Outcomes & Results

The results indicated that only higher intensity treatment (2×/week) led to significantly better outcomes for articulation and functional communication compared with 1×/week (lower intensity) intervention. Further, neither lower nor higher intensity treatment yielded a significant change for speech intelligibility at the word or sentence level. In general, effect sizes for the higher intensity treatment groups were larger for most variables compared with the lower intensity treatment group.

Conclusions & Implications

Overall, the results of the current study may allow for modification of service delivery and facilitate the development of an evidence‐based care pathway for children with CAS.
Avoiding Another ‘Squatter in Downing Street’ Controversy: The Need to Improve the Caretaker Conventions before the 2015 General Election
Authors: SCHLEITER PETRA , BELU VALERIE
Published: January 2015

In the UK the rules governing caretaker situations have historically been underspecified. The UK's constitutional traditions, such as prime ministerial discretion to time elections and its two‐party system, have in the past limited the frequency and duration of caretaker periods. However, the recently lengthened election timetable, new constraints on the executive introduced by the Fixed‐term Parliaments Act (2011), and a decline in the dominance of the two largest parties are raising the risk that the UK will experience caretaker periods more often and for longer stretches of time. In this paper, we offer an analysis of the UK's current caretaker provisions and conclude that the existing conventions are insufficiently detailed and can render such periods problematic and controversy‐prone. Important lessons, we suggest, can be learned from reforms in other Westminster systems, and from the caretaker rules of other countries.
Parents in Parliament: ‘Where's Mum?’
Authors: CAMPBELL ROSIE , CHILDS SARAH
Published: January 2015

There has been extensive consideration of women's under‐representation in the UK parliament. Here we are interested not only in the question of sex and political representation, but in parenthood too: in short, whether national politics is closed to women, and possibly men, with young children. We start with a review of the academic literature on legislative recruitment to see what it has to say about mothers—almost nothing has been written about fathers. Based on a 2013 survey of UK MPs—men and women—we then identify key features of parents' presence at Westminster. For the first time, we can be sure that mothers are in fact significantly under‐represented in the House of Commons. We then consider whether arguments made to support the descriptive representation of women have purchase for mothers. Finally we consider how political institutions might be reconfigured not to be merely woman or even mother‐friendly, but to be care‐friendly.
Male Perpetrators of Domestic Violence: How Should We Hold Them to Account?
Authors: DEVANEY JOHN
Published: January 2015

Domestic violence is now widely acknowledged as being a significant social, health and legal issue. At both a national and transnational level governments have sought to develop strategies built upon prevention, support for victims and holding perpetrators to account through criminal justice sanctions. However, the current paradigm that informs the policy response to most perpetrators of domestic violence has failed to deliver the outcomes required, in terms of a reduction in levels of recidivism or the improved safety of women and children. It is argued that holding men to account through external controls has failed and that interventions should support men to take responsibility for their own behaviour.
An Invidious Position? The Public Dance of the Promiscuous Partisan
Authors: GRUBE DENNIS
Published: January 2015

Public service mandarins were once largely anonymous, diligently wielding their great power behind the scenes while their political masters performed on the front stage. Things have changed. Today, civil service leaders are appearing publicly more often, in more places and to a wider range of audiences than ever before. This article examines the extent to which this decline in anonymity impacts on traditions of civil service impartiality within the Westminster system. It draws on the late Peter Aucoin's concept of ‘promiscuous partisanship’ to examine how contemporary mandarins in the United Kingdom, Canada and Australia face accusations of having compromised their impartiality by advocating for the policy agenda of the government of the day. The article argues that what has changed is not that civil service leaders have suddenly become partisan, but rather that they have become more ‘public’, allowing for perceptions of partisanship to emerge.
The Club Rules in Global Financial Governance
Authors: TSINGOU ELENI
Published: January 2015

Though the list of reforms following the onset of the financial crisis is long, we should resist the temptation to view the emerging regulatory framework in terms of a paradigm shift. Many key features of the system, including the privileged position of financial institutions, remain unchanged. This is not merely due to obstruction or capacity shortcomings but can be explained by considering the sources of ideas and the governance setting. Ideas and policy programmes for reform were generated by a policy community also responsible for shaping the pre‐crisis governance framework. Moreover, the ideas and preferences of these players are moulded by their transnational interactions and the club‐like mechanisms in place for determining what (and who) is to be included in discussions. These settings have produced policy programmes that helped address the immediate, ‘fast‐burning’ elements of the crisis, but have so far failed to put together a comprehensive reform programme.
The Boom, the Bust and the Future of Homeownership
Authors: Gabriel Stuart A. , Rosenthal Stuart S.
Published: January 2015

This article investigates the boom and bust in U.S. homeownership rates over the 2000–2010 period. Using individual‐level census data, we first estimate 204 homeownership regressions stratified by household age (21, 22, …, 89) and survey year (2000, 2005 and 2009). Shift‐share methods confirm that changes in the model coefficients that reflect household attitudes, lending standards and other market conditions—but not population socioeconomics—were the primary driver of the boom and bust in homeownership over the decade. This pattern holds for nearly all age groups and is more pronounced for recent movers. Results also suggest that homeownership rates may have come close to bottoming out in early 2013 at 65% after falling roughly four percentage points from their peak in 2006. This suggests little lasting effect of the grand homeownership policy experiment of recent decades.
The Impact of LEED Neighborhood Certification on Condo Prices
Authors: Freybote Julia , Sun Hua , Yang Xi
Published: January 2015

The U.S. Green Building Council offers LEED certification for existing and new neighborhood developments that meet sustainable urban development standards. Features of sustainable urban development have been found to positively affect residential sales prices. We investigate whether the intangible labeling effects of LEED neighborhood certification add a premium to the sales prices of LEED and non‐LEED–certified condos. Using a quasi‐experiment, transaction data from Portland, Oregon, and a spatio‐temporal autoregressive (STAR) model, we find no evidence that the intangible labeling effects of LEED neighborhood certification directly or indirectly affect sales prices. Our results suggest that, contrary to LEED building certification, which we find adds a premium to condo sales prices, the LEED neighborhood label by itself fails to add value for condo buyers. Explanations for our findings include market acceptance, neighborhood delineation issues and the free rider problem as it relates to public goods.
Trends in access block 2011 to 2013: The Redcliffe National Emergency Access Target experience
Authors: Lawton Luke D , Thomas Simon , Morel Douglas G
Published: January 2015

Objective

To evaluate the impact of the introduction of National Emergency Access Target (NEAT) on access block and long‐stay patients in Redcliffe Hospital ED, and to evaluate the possibility of forward compliance with the 2014 and 2015 NEAT thresholds.

Setting and Design

Redcliffe hospital is a major urban district hospital in Brisbane with more than 55 000 adult and paediatric patients per annum. We evaluated aggregate Emergency Department Information System data for the years 2011, 2012 and 2013 to correlate presentations, NEAT compliance, access block and the number of long‐stay patients in our department.

Results

There has been a significant reduction in both access block and our number of long‐stay patients corresponding with improvements in NEAT compliance. Our forward analysis suggests that without substantial improvements in the NEAT for admitted patients, compliance with 2014 and 2015 thresholds is unlikely to be achievable.

Conclusions

NEAT has been a driver of significant improvements in access block at our institution. We see significant issues with raising the NEAT threshold to the proposed 90% in 2015, and support recent calls for re‐evaluation and modification of the target.
Utilization of the International Association for the Study of Lung Cancer and Wang's nodal map for the identification of mediastinum and hilar lymph nodes
Authors: Xia Yang , Ma Yun , Arias Sixto , Lee Hans , Wang Ko‐Pen
Published: January 2015

Background

Transbronchial needle aspiration (TBNA), serving as a remarkably invaluable and minimally invasive technique, has been widely used for the diagnosis and staging of mediastinal adenopathy and masses. To date, the International Association for the Study of Lung Cancer (IASLC) and Wang's nodal map are two well‐documented intrathoracic lymph node guidelines for the TBNA procedure.

Method

We characterized IASLC's and Wang's map, and interpreted the correlation of the two maps station by station.

Results

The pivotal role of IASLC map is to determine N descriptor in the tumor node metastasis (TNM) staging system of lung cancer, whilst Wang's map is employed to facilitate the localization of biopsy sites for bronchoscopists during TBNA performance. Furthermore, stations 1, 3 and 5 in Wang’ map are equivalent to 4R station in IASLC’ system, while stations 4 and 6 in Wang's account for IASLC station 4L as N2 stations. In addition, Wang's stations 2, 8 and 10 are correlated with station 7 in IASLC's. Wang's stations 7 and 9 are responsible for station 11R in IASLC's map.

Conclusion

Given their unique benefits and limitations, and the practical links between the two maps, it appears reasonable to highlight the significance of their complementary utilization upon TBNA performance and lung cancer staging.
The Prevalence and clinical characteristics of primary Sjogren's syndrome patients with lung cancer: An analysis of ten cases in China and literature review
Authors: Xu Yan , Fei Yunyun , Zhong Wei , Zhang Li , Zhao Jing , Li Longyun , Wang Mengzhao
Published: January 2015

Background

A retrospective analysis of clinical data from primary Sjogren's syndrome (pSS) patients with lung cancer was conducted in order to guide further clinical work.

Methods

From January 1993 to December 2010, 10 pSS patients with lung cancer were hospitalized at the Peking Union Medical College Hospital. One hundred and three pSS patients were recruited as the controls. Patients' clinical data was retrospectively analyzed.

Result

The incidence rate of lung cancer in pSS patients was 0.477%. The duration from diagnosis of pSS to lung cancer in the 10 patients was 0.92∼42 years. The pSS patients with lung cancer were significantly older than those without lung cancer (60.8 ± 8.9 vs. 44.9 ± 12.1, P < 0.001). Eight of the pSS patients with lung cancer (80%) were female nonsmokers; five pSS patients with lung cancer (50%) had lung involvement, exhibiting diffuse parenchymal lung disease. Adenocarcinoma was the most common pathological type of lung cancer (90%). Tumor node metastasis staging of lung cancer included: four cases of Ib (40%), one case of IIIb (10%), four cases of IV (40%) and one case undetermined (10%).

Conclusion

The incidence rate of lung cancer in pSS patients was higher with respect to the normal population. Physicians should closely observe lung cancer incidence during the pSS follow‐up period. Adenocarcinoma was the most frequently seen lung cancer pathology in pSS patients. Clinical stages and individualized treatment for pSS patients with lung cancer should be carefully determined.
Effects of the kappa opioid receptor antagonist nor‐binaltorphimine (nor‐BNI) on cocaine versus food choice and extended‐access cocaine intake in rhesus monkeys
Authors: Hutsell Blake A. , Cheng Kejun , Rice Kenner C. , Negus Sidney Stevens , Banks Matthew L.
Published: January 2015

The dynorphin/kappa opioid receptor (KOR) system has been implicated as one potential neurobiological modulator of the abuse‐related effects of cocaine and as a potential target for medications development. This study determined effects of the KOR antagonist nor‐binaltorphimine (nor‐BNI) on cocaine self‐administration under a novel procedure that featured two daily components: (1) a 2‐hour ‘choice’ component (9:00–11:00 am) when monkeys could choose between food pellets and cocaine injections (0–0.1 mg/kg per injection, intravenous) and (2) a 20‐hour ‘extended‐access’ component (noon to 8:00 am) when cocaine (0.1 mg/kg per injection) was available under a fixed‐ratio schedule to promote high daily cocaine intakes. Rhesus monkeys (n = 4) were given 14 days of exposure to the choice + extended‐access procedure then treated with nor‐BNI (3.2 or 10.0 mg/kg, intramuscular), and cocaine choice and extended‐access cocaine intake were evaluated for an additional 14 days. Consistent with previous studies, cocaine maintained both a dose‐dependent increase in cocaine choice during choice components and a high level of cocaine intake during extended‐access components. Neither 3.2 nor 10 mg/kg nor‐BNI significantly altered cocaine choice or extended‐access cocaine intake. In two additional monkeys, nor‐BNI also had no effect on cocaine choice or extended‐access cocaine intake when it was administered at the beginning of exposure to the extended‐access components. Overall, these results do not support a major role for the dynorphin/KOR system in modulating cocaine self‐administration under these conditions in non‐human primates nor do they support the clinical utility of KOR antagonists as a pharmacotherapeutic strategy for cocaine addiction.
Nicotine produces chronic behavioral sensitization with changes in accumbal neurotransmission and increased sensitivity to re‐exposure
Authors: Morud Julia , Adermark Louise , Perez‐Alcazar Marta , Ericson Mia , Söderpalm Bo
Published: January 2015

Tobacco use is often associated with long‐term addiction as well as high risk of relapse following cessation. This is suggestive of persistent neural adaptations, but little is known about the long‐lasting effects of nicotine on neural circuits. In order to investigate the long‐term effects of nicotine exposure, Wistar rats were treated for 3 weeks with nicotine (0.36 mg/kg), and the duration of behavioral and neurophysiological adaptations was evaluated 7 months later. We found that increased drug‐induced locomotion persisted 7 months after the initial behavioral sensitization. In vitro analysis of synaptic activity in the core and shell of the nucleus accumbens (nAc) revealed a decrease in input/output function in both regions of nicotine‐treated rats as compared to vehicle‐treated control rats. In addition, administration of the dopamine D2 receptor agonist quinpirole (5 μM) significantly increased evoked population spike amplitude in the nAc shell of nicotine‐treated rats as compared to vehicle‐treated control rats. To test whether nicotine exposure creates long‐lasting malleable circuits, animals were re‐exposed to nicotine 7 months after the initial exposure. This treatment revealed an increased sensitivity to nicotine among animals previously exposed to nicotine, with higher nicotine‐induced locomotion responses than observed initially. In vitro electrophysiological recordings in re‐exposed rats detected an increased sensitivity to dopamine D2 receptor activation. These results suggest that nicotine produces persistent neural adaptations that make the system sensitive and receptive to future nicotine re‐exposure.
Investor Sentiment, Product Features, and Advertising Investment Sensitivities
Authors: Luo Miao , Jiang Daniel X. , Cai Jun
Published: January 2015

Investor sentiment plays an important role, affecting firm level advertising expenditures. We provide evidence that financially constrained firms exhibit lower advertising investment‐cash flow sensitivity and higher advertising investment‐q sensitivity during high sentiment periods. The patterns are driven mainly by those firms facing financial constraints. More importantly, we identify several product features that also affect advertising investment sensitivities. Sorting on product features generates investment sensitivities that closely resemble those of sorting on financial constraint measures. We design empirical analyses to provide clean tests of the cost‐of‐external‐financing‐based and product‐feature‐based explanations underlying the variation in advertising investment sensitivities.
Powerful CEOs and Corporate Governance: Evidence from an Analysis of CEO and Director Turnover After Fraud
Authors: Johnson William C. , Yi Sangho
Published: January 2015

In this paper, we investigate the consequences of fraud for CEOs and whether these consequences depend on CEO power. We find that CEO power can reduce the likelihood of director turnover as well as CEO turnover after fraud detection. Further, we find that CEO power is negatively related to long‐term stock performance after fraud detection and this negative relationship is particularly strong for powerful CEOs when the board has a low overall turnover. These results imply that powerful CEOs can entrench themselves and survive corporate turbulence by potentially working with board members who are favorable to them.
Computational fluid dynamic modelling of the effect of ventilation mode and tracheal tube position on air flow in the large airways
Authors: Lumb A. B. , Burns A. D. , Figueroa Rosette J. A. , Gradzik K. B. , Ingham D. B. , Pourkashanian M.
Published: January 2015

We have used computational fluid dynamic modelling to study the effects of tracheal tube size and position on regional gas flow in the large airways. Using a three‐dimensional mathematical model, we simulated flow with and without a tracheal tube, replicating both physiological and artificial breathing. Ventilation through a tracheal tube increased proportional flow to the left lung from 39.5% with no tube to 43.1–47.2%, depending on tube position. Ventilation mode and tube distance from the carina had no effect on flow. Lateral displacement and deflection of the tube increased ventilation to the ipsilateral lung; for example, when deflected 10° to the left of centre, flow to the left lung increased from 43.8 to 53.7%. Because of the small diameter of a tracheal tube relative to the trachea, gas exits a tube at high velocity such that regional ventilation may be affected by changes in the position and angle of the tube.
The effect of early in‐hospital medication review on health outcomes: a systematic review
Authors: Hohl Corinne M. , Wickham Maeve E. , Sobolev Boris , Perry Jeff J. , Sivilotti Marco L. A. , Garrison Scott , Lang Eddy , Brasher Penny , Doyle‐Waters Mary M. , Brar Baljeet , Rowe Brian H. , Lexchin Joel , Holland Richard
Published: January 2015

Aims

Adverse drug events are an important cause of emergency department visits, unplanned admissions and prolonged hospital stays. Our objective was to synthesize the evidence on the effect of early in‐hospital pharmacist‐led medication review on patient‐oriented outcomes based on observed data.

Methods

We systematically searched eight bibliographic reference databases, electronic grey literature, medical journals, conference proceedings, trial registries and bibliographies of relevant papers. We included studies that employed random or quasi‐random methods to allocate subjects to pharmacist‐led medication review or control. Medication review had to include, at a minimum, obtaining a best possible medication history and reviewing medications for appropriateness and adverse drug events. The intervention had to be initiated within 24 h of emergency department presentation or 72 h of admission. We extracted data in duplicate and pooled outcomes from clinically homogeneous studies of the same design using random effects meta‐analysis.

Results

We retrieved 4549 titles of which seven were included, reporting the outcomes of 3292 patients. We pooled data from studies of the same design, and found no significant differences in length of hospital admission (weighted mean difference [WMD] –0.04 days, 95% confidence interval [CI] –1.63, 1.55), mortality (odds ratio [OR] 1.09, 95% CI 0.69, 1.72), readmissions (OR 1.15, 95% CI 0.81, 1.63) or emergency department revisits at 3 months (OR 0.60, 95% CI 0.27, 1.32). Two large studies reporting reductions in readmissions could not be included in our pooled estimates due to differences in study design.

Conclusions

Wide confidence intervals suggest that additional research is likely to influence the effect size estimates and clarify the effect of medication review on patient‐oriented outcomes. This systematic review failed to identify an effect of pharmacist‐led medication review on health outcomes.
Quality and safety of herbal medical products: regulation and the need for quality assurance along the value chains
Authors: Heinrich Michael
Published: January 2015

Herbal medicines and products derived from them are a diverse group of products for which different (and often limited) levels of evidence are available. As importantly, such products generally vary in their composition and are at the end of an often poorly understood value chain, which often links producers in biodiversity rich countries with the large markets in the North. This paper discusses the current regulatory framework of such herbal medical products (with a focus on the UK) and using examples from our own metabolomic research on Curcumal longa L. (turmeric, Zingiberaceae) how value chains impact on the composition and quality (and thus the safety) of such products.

Overall, our recent research demonstrates the need for studying the links between producers and consumers of commodities produced in provider countries and that plant metabolomics offer a novel way of assessing the chemical variability along a value chain.
DO BALANCED‐BUDGET RULES INCREASE GROWTH?
Authors: Stone Joe A.
Published: January 2015

This study tests the hypothesis that balanced‐budget rules (BBRs) that restrict public borrowing to investments in public infrastructure increase growth by increasing the productivity of debt, either because investments in public infrastructure are more productive than other uses for which states borrow funds or because BBRs lower borrowing costs. Results are based on data at 5‐year intervals for 49 US states over the period 1957–2007. The tests strongly support the hypothesis that BBRs increase growth by increasing the productivity of debt and withstand a variety of robustness checks, including alternative lags, exogeneity tests, GMM estimation, a placebo test, and the influence of outliers.
Distinctive expression patterns of glycoprotein non‐metastatic B and folliculin in renal tumors in patients with Birt–Hogg–Dubé syndrome
Authors: Furuya Mitsuko , Hong Seung‐Beom , Tanaka Reiko , Kuroda Naoto , Nagashima Yoji , Nagahama Kiyotaka , Suyama Takahito , Yao Masahiro , Nakatani Yukio
Published: January 2015

Birt–Hogg–Dubé syndrome (BHD) is an inherited disorder associated with a germline mutation of the folliculin gene (FLCN). The affected families have a high risk for developing multiple renal cell carcinomas (RCC). Diagnostic markers that distinguish between FLCN‐related RCC and sporadic RCC have not been investigated, and many patients with undiagnosed BHD fail to receive proper medical care. We investigated the histopathology of 27 RCCs obtained from 18 BHD patients who were diagnosed by genetic testing. Possible somatic mutations of RCC lesions were investigated by DNA sequencing. Western blotting and immunohistochemical staining were used to compare the expression levels of FLCN and glycoprotein non‐metastatic B (GPNMB) between FLCN‐related RCCs and sporadic renal tumors (n = 62). The expression of GPNMB was also evaluated by quantitative RT‐PCR. Histopathological analysis revealed that the most frequent histological type was chromophobe RCC (n = 12), followed by hybrid oncocytic/chromophobe tumor (n = 6). Somatic mutation analysis revealed small intragenic mutations in six cases and loss of heterozygosity in two cases. Western blot and immunostaining analyses revealed that FLCN‐related RCCs showed overexpression of GPNMB and underexpression of FLCN, whereas sporadic tumors showed inverted patterns. GPNMB mRNA in FLCN‐related RCCs was 23‐fold more abundant than in sporadic tumors. The distinctive expression patterns of GPNMB and FLCN might identify patients with RCCs who need further work‐up for BHD.
Overexpression of chemokine receptor CXCR2 and ligand CXCL7 in liver metastases from colon cancer is correlated to shorter disease‐free and overall survival
Authors: Desurmont Thibault , Skrypek Nicolas , Duhamel Alain , Jonckheere Nicolas , Millet Guillaume , Leteurtre Emmanuelle , Gosset Pierre , Duchene Belinda , Ramdane Nassima , Hebbar Mohamed , Van Seuningen Isabelle , Pruvot François‐René , Huet Guillemette , Truant Stéphanie
Published: January 2015

Our aim was to analyze the potential role of chemokine receptors CXCR2 and CXCR4 signalling pathways in liver metastatic colorectal cancer (CRC) relapse. CXCR2, CXCR4, and their chemokine ligands were evaluated in liver metastases of colorectal cancer in order to study their correlation with overall and disease‐free survival of patients having received, or not received, a neoadjuvant chemotherapy regimen. Quantitative RT‐PCR and CXCR2 immunohistochemical staining were carried out using CRC liver metastasis samples. Expression levels of CXCR2, CXCR4, and their ligands were statistically analyzed according to treatment with neoadjuvant chemotherapy and patients’ outcome. CXCR2 and CXCL7 overexpression are correlated to shorter overall and disease‐free survival. By multivariate analysis, CXCR2 and CXCL7 expressions are independent factors of overall and disease‐free survival. Neoadjuvant chemotherapy increases significantly the expression of CXCR2: treated group 1.89 (0.02–50.92) vs 0.55 (0.07–3.22), P = 0.016. CXCL7 was overexpressed close to significance, 0.40 (0.00–7.85) vs 0.15 (0.01–7.88), P = 0.12. We show the involvement of CXCL7/CXCR2 signalling pathways as a predictive factor of poor outcome in metastatic CRC. 5‐Fluorouracil‐based chemotherapy regimens increase the expression of these genes in liver metastasis, providing one explanation for aggressiveness of relapsed drug‐resistant tumors. Selective blockage of CXCR2/CXCL7 signalling pathways could provide new potential therapeutic opportunities.
Antimicrobial Peptides Derived from Fusion Peptides of Influenza A Viruses, a Promising Approach to Designing Potent Antimicrobial Agents
Authors: Wang Jingyu , Zhong Wenjing , Lin Dongguo , Xia Fan , Wu Wenjiao , Zhang Heyuan , Lv Lin , Liu Shuwen , He Jian
Published: January 2015

The emergence and dissemination of antibiotic‐resistant bacterial pathogens have spurred the urgent need to develop novel antimicrobial agents with different mode of action. In this respect, we turned several fusogenic peptides (FPs) derived from the hemagglutinin glycoproteins (HAs) of IAV into potent antibacterials by replacing the negatively or neutrally charged residues of FPs with positively charged lysines. Their antibacterial activities were evaluated by testing the MICs against a panel of bacterial strains including S. aureus, S. mutans, P. aeruginosa, and E. coli. The results showed that peptides HA‐FP‐1, HA‐FP‐2‐1, and HA‐FP‐3‐1 were effective against both Gram‐positive and Gram‐negative bacteria with MICs ranging from 1.9 to 16.0 μm, while the toxicities toward mammalian cells were low. In addition, the mode of action and the secondary structure of these peptides were also discussed. These data not only provide several potent peptides displaying promising potential in development as broad antimicrobial agents, but also present a useful strategy in designing new antimicrobial agents.
Decreased FEV1% in asthmatic adults in Scottish homes with high Environmental Relative Moldiness Index values
Authors: McSharry C. , Vesper S. , Wymer L. , Howieson S. , Chaudhuri R. , Wright G. R. , Thomson N. C.
Published: January 2015

Background

Exposures to indoor biological contaminants have been implicated in asthma's aetiology but their effect on lung function is not well quantified.

Objective

The aim of this cross‐sectional study of non‐smoking, asthmatic adults in Scotland was to determine the correlation between the results from a standard spirometry test, forced expiratory volume in one‐second percent (FEV1%), and quantitative estimates of some biological exposures.

Methods

A population (n = 55) of non‐smoking, adult asthmatics in Scotland was included in this study and each completed a questionnaire that allowed the determination of the Asthma Control Questionnaire scores (ACQ) and St. George's Respiratory Questionnaire scores (SGRQ), as well as corticosteroid use. Spirometry testing was completed and the pre‐bronchodilator FEV1% value calculated. At about the same time, floor dust samples were collected in the living room and in the bedroom. These dust samples were analysed for mould contamination, as described by the Environmental Relative Moldiness Index (ERMI) values and by (1, 3)‐β‐D‐glucan concentrations, for endotoxin, and for dust mite, cat, and dog allergen concentrations. The asthmatics' FEV1% values were tested for correlation (Pearson) to questionnaire‐based estimates of health. Also, each biological exposure was tested for correlation (Pearson) to the FEV1% values.

Results

FEV1% results were correlated with ACQ scores (ρ −0.586, P < 0.001), SGRQ scores (ρ −0.313, P = 0.020), and weakly with corticosteroid use (ρ −0.221, P = 0.105). The ERMI values in the homes (average 5.3) were significantly correlated with FEV1% values (ρ −0.378, P = 0.004). There was no correlation between FEV1% and concentrations of endotoxin, (1, 3)‐β‐D‐glucan, or any of the allergens.

Conclusion and clinical relevance

Although these results do not prove that mould exposures caused the deficit in lung function observed in this study, it might be advisable for asthmatics to avoid high ERMI environments.
Immunological potential of cytotoxic T lymphocyte antigen 4 immunoglobulin in murine autoimmune cholangitis
Authors: Tanaka H , Yang G-X , Tomiyama T , Tsuneyama K , Zhang W , Leung P S C , Coppel R L , Joh T , Nadler S G , Ansari A A , Bowlus C , Gershwin M E
Published: January 2015

Cytotoxic T lymphocyte antigen 4 (CTLA-4) immunoglobulin (Ig) is an important regulator of T cell activation and a fusion protein directed at CD80 and CD86; it blocks co-stimulatory signalling and T cell activation. We have taken advantage of a murine model of human primary biliary cirrhosis (PBC), mice expressing a transforming growth factor (TGF)-β receptor II dominant negative (dnTGF-βRII) transgene to address the potential therapeutic efficacy of CTLA-4 Ig. To mimic patients with PBC at different stages or duration of disease, we treated mice with either CTLA-4 Ig or control IgG three times weekly from 3 to 12 or 24 weeks of age, or from 12 to 24 weeks of age. CTLA-4 Ig treatment from 3 weeks of age significantly reduced liver inflammation to 12 weeks of age. Treatment initiated at 12 weeks of age also ameliorated the autoimmune cholangitis at 24 weeks of age. However, in mice treated at 3 weeks of age, suppression of liver inflammation was not sustained and colitis was aggravated when treatment was extended to 24 weeks of age. Our data indicate that, in dnTGF-βRII mice, CTLA-4 Ig treatment has short-term beneficial effects on autoimmune cholangitis, but the effect varies according to duration of treatment and the time in which therapy was initiated. Further dissection of the events that lead to the reduction in therapeutic effectiveness of CTLA-4 Ig will be critical to determining whether such efforts can be applied to human PBC.
Characterization and functional studies of forkhead box protein 3− lymphocyte activation gene 3+ CD4+ regulatory T cells induced by mucosal B cells
Authors: Chu K-H , Chiang B-L
Published: January 2015

The induction of mucosal tolerance has been demonstrated to be an effective therapeutic approach for the treatment of allergic diseases. Our previous study demonstrated that Peyer's patch B cells could convert naive T cells into regulatory T cells (so-called Treg-of-B(P) cells); however, it is important to characterize this particular subset of Treg-of-B cells for future applications. This study aimed to investigate the role of lymphocyte activating gene 3 (LAG3) in mediating the regulatory function of Treg-of-B(P) cells induced by mucosal follicular B (FOB) cells. Microarray analysis and real-time polymerase chain reaction (PCR) were used to assess the gene expression pattern of Treg-of-B(P) cells. To evaluate the role of LAG3, the in-vitro suppressive function and the alleviation of airway inflammation in a murine model of asthma was assessed. Our data indicated that FOB cells isolated from Peyer's patches had the ability to generate more suppressive Treg-of-B cells with LAG3 expression, compared with CD23loCD21loB cells. LAG3 is not only a marker for Treg-of-B(P) cells, but also participate in the suppressive ability. Moreover, CCR4 and CCR6 could be detected on the LAG3+, not LAG3−, Treg-of-B(P) cells and would help cells homing to allergic lung. In the murine model of asthma, the adoptive transfer of LAG3+Treg-of-B(P) cells was able to sufficiently suppress T helper type 2 (Th2) cytokine production, eosinophil infiltration and alleviate asthmatic symptoms. LAG3 was expressed in Treg-of-B(P) cells and was also involved in the function of Treg-of-B(P) cells. In the future, this particular subset of Treg-of-B cells might be used to alleviate allergic symptoms.
Dipeptidyl peptidase‐4 inhibitors and the risk of community‐acquired pneumonia in patients with type 2 diabetes
Authors: Faillie J.‐L. , Filion K. B. , Patenaude V. , Ernst P. , Azoulay L.
Published: January 2015

Aims

To determine whether the use of dipeptidyl peptidase‐4 (DPP‐4) inhibitors is associated with an increased risk of community‐acquired pneumonia.

Methods

The UK Clinical Practice Research Datalink and the Hospital Episodes Statistics database were used to conduct a nested case–control analysis within a cohort of new users of antidiabetic drugs between 2007 and 2012. Incident cases of hospitalization for community‐acquired pneumonia were matched with up to 20 controls on age, duration of treated diabetes, calendar year and duration of follow‐up. Conditional logistic regression models were used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for hospitalization for community‐acquired pneumonia associated with current use of DPP‐4 inhibitors compared with current use of two or more oral antidiabetic drugs.

Results

The cohort included 49 653 patients, of whom 562 were hospitalized for community‐acquired pneumonia during follow‐up (incidence rate 5.2/1000 person‐years). Compared with current use of two or more oral antidiabetic drugs, current use of DPP‐4 inhibitors was not associated with an increased risk of hospitalized community‐acquired pneumonia overall (adjusted OR 0.80, 95% CI 0.50–1.29) or according to duration of use (p for trend = 0.57).

Conclusions

The use of DPP‐4 inhibitors was not associated with an increased risk of hospitalization for community‐acquired pneumonia. Additional research is needed to assess the association between these drugs and other serious infections.
Sitagliptin, a dipeptidyl peptidase‐4 inhibitor, improves recognition memory, oxidative stress and hippocampal neurogenesis and upregulates key genes involved in cognitive decline
Authors: Gault V. A. , Lennox R. , Flatt P. R.
Published: January 2015

Aim

To examine whether prolonged dipeptidyl peptidase‐4 (DPP‐4) inhibition can reverse learning and memory impairment in high‐fat‐fed mice.

Methods

High‐fat‐fed mice received oral sitagliptin (50 mg/kg body weight) once daily or saline vehicle over 21 days. An additional group of mice on standard chow received saline vehicle. Energy intake, body weight, glucose and insulin concentrations were measured at regular intervals. Glucose tolerance, insulin sensitivity, novel object recognition, DPP‐4 activity, hormone analysis, hippocampal gene expression and histology were performed.

Results

Sitagliptin decreased circulating DPP‐4 activity and improved glucose tolerance, glucose‐stimulated insulin secretion and insulin sensitivity, and reduced plasma triglycerides and cholesterol levels. DPP‐4 inhibition improved recognition memory (1.2‐fold increase) without affecting hypermoteric activity or anxiety levels. Improvement in memory and learning was linked to reduced immunostaining for 8‐oxoguanine and increased doublecortin staining in the hippocampus, which were indicative of reduced brain oxidative stress and increased hippocampal neurogenesis, respectively. These effects were associated with significant upregulation of hippocampal gene expression of glucagon‐like peptide‐1 (GLP‐1) receptor, glucose‐dependent insulinotropic polypeptide receptor, synaptophysin, sirtuin 1, glycogen synthase kinase 3β, superdioxide mutase 2, nuclear factor (erythroid‐derived 2)‐like 2 and vascular endothelial growth factor. Total plasma and brain GLP‐1 concentrations were significantly increased after sitagliptin therapy, whereas DPP‐4 activity in brain tissue was not altered.

Conclusion

These studies show that sitagliptin can reverse memory impairment in high‐fat‐fed mice and is also associated with improved insulin sensitivity, enhanced hippocampal neurogenesis and reduced oxidative stress. DPP‐4 inhibitors may therefore exhibit dual benefits by improving metabolic control and reducing the decline in cognitive function.
What is Education For? On Good Education, Teacher Judgement, and Educational Professionalism
Authors: Biesta Gert
Published: January 2015

Teaching and teachers have recently become the centre of attention of policy makers and researchers. The general idea here is that teaching matters. Yet the question that is either not asked or is only answered implicitly is why teaching matters. In this article I engage with this question in the context of a wider discussion about the role, status and significance of the question of purpose in education. I suggest that this is the most fundamental question in all educational endeavours. It is a normative question which poses itself as a multi‐dimensional question, since education always functions in relation to three domains of purpose: qualification, socialisation and subjectification. Against this background I analyse the specific nature of teacher judgement in education and show how the space for teacher judgement is being threatened by recent developments in educational policy and practice that concern the status of the student, the impact of accountability and the role of evidence. I indicate how, where and why these are problematic and what this implies for regaining a space for teachers’ professional judgement.
No Short‐Term Contingency Between Grooming and Food Tolerance in Barbary Macaques (Macaca sylvanus)
Authors: Molesti Sandra , Majolo Bonaventura
Published: January 2015

The exchange of services such as allo‐grooming, allo‐preening, food tolerance and agonistic support has been observed in a range of species. Two proximate mechanisms have been proposed to explain the exchanges of services in animals. First, an animal can give a service to a partner depending on how the partner behaved towards it in the recent past. This mechanism is usually tested by examining the within‐dyad temporal relation between events given and received over short time periods. Second, the partner choice mechanism assumes that animals give favours towards specific partners but not others, by comparing how each partner behaved towards them over longer time frames. As such, the partner choice mechanism does not make specific predictions on a temporal contingency between services received and given over short time frames. While there is evidence for a long‐term positive correlation between services exchanged in animals, results for short‐term contingencies between services given and received are mixed. Our study investigated the exchange of grooming for food tolerance in a partially provisioned group of Barbary macaques, by analysing the short‐term contingency between these events. Tolerance over food was compared immediately after grooming and in control condition, using food of different shareability. We found no evidence that grooming increases food tolerance or decrease aggression around food in the short term. Food tolerance was affected by the shareability of the food and the sex of the partners. The exchanges of grooming and food tolerance in non‐human primates may be little affected by recent single events. We suggest that long‐term exchanges between services given and received and social partner choice may play a more important role in explaining social interactions than short‐term contingent events.