bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leadership styles used by senior medical leaders
Authors: Chapman Ann LN , Johnson David , Kilner Karen 
Published: November 2014

Purpose– The purpose of this study was to determine the predominant leadership styles used by medical leaders and factors influencing leadership style use. Clinician leadership is important in healthcare delivery and service development. The use of different leadership styles in different contexts can influence individual and organisational effectiveness.Design/methodology/approach– A mixed methods approach was used, combining a questionnaire distributed electronically to 224 medical leaders in acute hospital trusts with in-depth “critical incident” interviews with six medical leaders. Questionnaire responses were analysed quantitatively to determine, first, the overall frequency of use of six predefined leadership styles and, second, individual leadership style based on a consultative/decision-making paradigm. Interviews were analysed thematically using both a confirmatory approach with predefined leadership styles as themes, and also an inductive grounded theory approach exploring influencing factors.Findings– Leaders used a range of styles, the predominant styles being democratic, affiliative and authoritative. Although leaders varied in their decision-making authority and consultative tendency, virtually all leaders showed evidence of active leadership. Organisational culture, context, individual propensity and “style history” emerged during the inductive analysis as important factors in determining use of leadership styles by medical leaders.Practical implications– The outcomes of this evaluation are useful for leadership development at the level of the individual, organisation and wider National Health Service (NHS).Originality/value– This study adds to the very limited evidence base on patterns of leadership style use in medical leadership and reports a novel conceptual framework of factors influencing leadership style use by medical leaders.
Skin sloughing rate increases with chytrid fungus infection load in a susceptible amphibian
Authors: Ohmer Michel E.B. , Cramp Rebecca L. , White Craig R. , Franklin Craig E. 
Published: November 2014

Summary

Amphibian chytridiomycosis, caused by the fungal pathogen Batrachochytrium dendrobatidis (Bd), is responsible for the greatest disease‐driven loss of vertebrate biodiversity in recorded history. Understanding drivers of host susceptibility to this cutaneous disease is hindered by gaps in our knowledge of the host–pathogen relationship. One such overlooked aspect of susceptibility is variation in skin maintenance processes, particularly skin turnover via routine sloughing. It has been suggested that sloughing plays a role in immune defence, by removing skin‐associated microbes. Thus, skin sloughing may play an important role in the pathogenesis of chytridiomycosis.

To determine the relationship between skin sloughing and disease progression, we exposed adult Australian green tree frogs (Litoria caerulea) to a local Bd strain and monitored sloughing rates and individual infection loads on a naturalistic cycling temperature regime (15–23 °C).

We determined sloughing rates in real‐time by using an array of infrared video cameras to film frog behaviour and monitored infection load before and after sloughing by swabbing and analysis with quantitative PCR.

We found that sloughing rate increased with Bd infection load in infected frogs, but sloughing itself did not affect Bd load on the ventral skin surface. Furthermore, Bd infection did not affect the duration of characteristic sloughing behaviour, and sloughing retained rhythmicity even at high infection loads.

Although an increased sloughing rate might be considered advantageous for Bd‐infected animals, it does not appear to curb the progression of disease and may actually contribute to the loss of physiological homoeostasis seen in terminally ill frogs by further inhibiting water and electrolyte transport across the skin.

By measuring sloughing rates directly for the first time, our results shed light on how Bd interacts with the physiological processes of the skin and indicate that variation in skin sloughing frequency may play a role in the observed inter‐ and intraspecific variation in susceptibility to disease.
Implementation aspects of eigendecomposition‐based high‐resolution velocity spectra
Authors: Barros Tiago , Lopes Renato , Tygel Martin 
Published: November 2014

ABSTRACTIn this paper, we discuss high‐resolution coherence functions for the estimation of the stacking parameters in seismic signal processing. We focus on the Multiple Signal Classification which uses the eigendecomposition of the seismic data to measure the coherence along stacking curves. This algorithm can outperform the traditional semblance in cases of close or interfering reflections, generating a sharper velocity spectrum. Our main contribution is to propose complexity‐reducing strategies for its implementation to make it a feasible alternative to semblance. First, we show how to compute the multiple signal classification spectrum based on the eigendecomposition of the temporal correlation matrix of the seismic data. This matrix has a lower order than the spatial correlation used by other methods, so computing its eigendecomposition is simpler. Then we show how to compute its coherence measure in terms of the signal subspace of seismic data. This further reduces the computational cost as we now have to compute fewer eigenvectors than those required by the noise subspace currently used in the literature. Furthermore, we show how these eigenvectors can be computed with the low‐complexity power method. As a result of these simplifications, we show that the complexity of computing the multiple signal classification velocity spectrum is only about three times greater than semblance. Also, we propose a new normalization function to deal with the high dynamic range of the velocity spectrum. Numerical examples with synthetic and real seismic data indicate that the proposed approach provides stacking parameters with better resolution than conventional semblance, at an affordable computational cost.
The Ten Commandments of Applied Regional Integration Analysis: The African Case
Authors: Charaf‐Eddine Naym , Strauss Ilan 
Published: November 2014

AbstractThis paper offers ten guidelines for researchers to improve their analysis of regional integration and their approach to regional integration. By way of analysis, regional integration statistics are often misunderstood or poorly constructed. In one way or another this leads to an oversimplification of their meaning. With respect to the approach taken by policymakers to regional integration, the goals of Africa's regional integration have not been seriously interrogated; nor have the necessary national and regional preconditions for achieving even a minimal form of regional integration that is sustainable.
The Will to Integrate: South Africa's Responses to Regional Migration from the SADC Region
Authors: Nshimbi Christopher Changwe , Fioramonti Lorenzo 
Published: November 2014

AbstractThis paper surveys frameworks of labour migration in southern Africa and determines South Africa's policy responses to inflows of migrants from seven neighbouring countries. Legislations, policy reports and scientific publications on migration were thoroughly reviewed and interviews and correspondence with key policymakers were conducted. Statistical analyses of data on foreign worker recruitments and permits issued by South Africa's Department of Home Affairs were also performed. The absence of a migration protocol in southern Africa suggests SADC Members have not implemented the African Union's migration policy basic guidelines. Two systems coexist in southern Africa that complicate migration governance: a South Africa‐managed bilateral migration policy, and aspirations for a formal SADC‐managed migration policy. Bilateral agreements between South Africa and neighbours have established a labour migration system that dims prospects for a regional migration policy. SACU Members could establish a two‐tier policy to achieve free movement while maintaining managed migration policy outside SACU. An official multilateral migration governance mechanism would serve SADC better than the current ad‐hoc measures.
Factors Behind Dialysis Patient Satisfaction: Exploring Their Effects on Overall Satisfaction
Authors: Gu Xiuzhu , Itoh Kenji 
Published: November 2014

AbstractWe would establish a construct of dialysis patients' satisfaction and identify their contribution to overall satisfaction. We also seek to identify present satisfaction levels of Japanese dialysis patients and some important characteristics of their satisfaction/dissatisfaction. A self‐administered questionnaire for measuring dialysis patient satisfaction was developed, which comprised 32 closed‐ended satisfaction question items that were facet‐specific, three items on overall satisfaction, four items on respondent's health status and quality of life as well as demographic information. Reliability and validity of the questionnaire was verified. A questionnaire‐based survey was conducted between July and September 2013. A total of 807 valid responses (63% of response rate) were collected from dialysis patients in 22 facilities located in most regions of Japan. Seven satisfaction factors were derived with 65% of cumulative variance accounted for by applying principal component analysis to responses to facet‐specific satisfaction items. More than 80% of patients expressed positive overall satisfaction and that they wished to continue dialysis therapy in the current facility (they can change dialysis facilities if they wish to). Dialysis patients' overall satisfaction was formulated significantly by five out of seven satisfaction factors by regression analysis. Japanese dialysis patients expressed their high satisfaction with and strong loyalty to the facility where they currently receive dialysis therapy (i.e., patient loyalty). The more satisfied dialysis patients were with the facility, the stronger loyalty they would like to maintain. The overall satisfaction was critically determined by their satisfaction with clinical environment, equipment, treatment and therapy. In addition, patients' quality of life was highly associated with their overall satisfaction.
Effects of Elevated Temperature Postharvest on Color Aspect, Physiochemical Characteristics, and Aroma Components of Pineapple Fruits
Authors: Liu Chuanhe , Liu Yan 
Published: November 2014

AbstractIn this work, 2 separate experiments were performed to describe the influence of elevated temperature treatments postharvest on the color, physiochemical characteristics and aroma components of pineapple fruits during low‐temperature seasons. The L* (lightness) values of the skin and pulp of pineapple fruits were decreased. The a* (greenness‐redness) and b* (blueness‐yellowness) values of the skin and pulp were all markedly increased. The elevated temperature significantly increased the contents of total soluble solids (TSS) and slightly affected contents of vitamin C (nonsignificant). Titratable acidity (TA) of pineapple fruits were notably decreased, whereas the values of TSS/TA of pineapple fruits were significantly increased. The firmness of the pineapple fruits decreased and more esters and alkenes were identified. The total relative contents of esters were increased, and the total relative contents of alkenes were decreased.
Synthesis and SAR studies of novel 6,7,8‐substituted 4‐substituted benzyloxyquinolin‐2(1H)‐one derivatives for anticancer activity
Authors: Chen Yi‐Fong , Lin Yi‐Chien , Morris‐Natschke Susan L , Wei Chen‐Fang , Shen Ting‐Chen , Lin Hui‐Yi , Hsu Mei‐Hua , Chou Li‐Chen , Zhao Yu , Kuo Sheng‐Chu , Lee Kuo‐Hsiung , Huang Li‐Jiau 
Published: November 2014

Background and Purpose4‐Phenylquinolin‐2(1H)‐one (4‐PQ) derivatives can induce cancer cell apoptosis. Additional new 4‐PQ analogs were investigated as more effective, less toxic antitumour agents.Experimental ApproachForty‐five 6,7,8‐substituted 4‐substituted benzyloxyquinolin‐2(1H)‐one derivatives were synthesized. Antiproliferative activities were evaluated using a 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazoliun bromide assay and structure–activity relationship correlations were established. Compounds 9b, 9c, 9e and 11e were also evaluated against the National Cancer Institute‐60 human cancer cell line panel. Hoechst 33258 and Annexin V‐FITC/PI staining assays were used to detect apoptosis, while inhibition of microtubule polymerization was assayed by fluorescence microscopy. Effects on the cell cycle were assessed by flow cytometry and on apoptosis‐related proteins (active caspase‐3, ‐8 and ‐9, procaspase‐3, ‐8, ‐9, PARP, Bid, Bcl‐xL and Bcl‐2) by Western blotting.Key ResultsNine 6,7,8‐substituted 4‐substituted benzyloxyquinolin‐2(1H)‐one derivatives (7e, 8e, 9b, 9c, 9e, 10c, 10e, 11c and 11e) displayed high potency against HL‐60, Hep3B, H460, and COLO 205 cancer cells (IC50 < 1 μM) without affecting Detroit 551 normal human cells (IC50 > 50 μM). Particularly, compound 11e exhibited nanomolar potency against COLO 205 cancer cells. Mechanistic studies indicated that compound 11e disrupted microtubule assembly and induced G2/M arrest, polyploidy and apoptosis via the intrinsic and extrinsic signalling pathways. Activation of JNK could play a role in TRAIL‐induced COLO 205 apoptosis.Conclusion and ImplicationsNew quinolone derivatives were identified as potential pro‐apoptotic agents. Compound 11e could be a promising lead compound for future antitumour agent development.
Protective effect of 23‐hydroxybetulinic acid on doxorubicin‐induced cardiotoxicity: a correlation with the inhibition of carbonyl reductase‐mediated metabolism
Authors: Zhou Fang , Hao Gang , Zhang Jingwei , Zheng Yuanting , Wu Xiaolan , Hao Kun , Niu Fang , Luo Dan , Sun Yuan , Wu Liang , Ye Wencai , Wang Guangji 
Published: November 2014

Background and PurposeThe clinical use of doxorubicin, an effective anticancer drug, is severely hampered by its cardiotoxicity. 23‐Hydroxybetulinic acid (23‐HBA), isolated from Pulsatilla chinensis, enhances the anticancer effect of doxorubicin while simultaneously reducing its cardiac toxicity, but does not affect the concentration of doxorubicin in the plasma and heart. As the metabolite doxorubicinol is more potent than doxorubicin at inducing cardiac toxicity, in the present study we aimed to clarify the role of doxorubicinol in the protective effect of 23‐HBA.Experimental ApproachDoxorubicin was administered to mice for two weeks in the presence or absence of 23‐HBA. The heart pathology, function, myocardial enzymes and accumulation of doxorubicin and doxorubicinol were then analysed. A cellular pharmacokinetic study of doxorubicin and doxorubicinol, carbonyl reductase 1 (CBR1) interference and molecular docking was performed in vitro.Key Results23‐HBA alleviated the doxorubicin‐induced cardiotoxicity in mice, and this was accompanied by inhibition of the metabolism of doxorubicin and reduced accumulation of doxorubicinol selectively in hearts. In H9c2 cells, the protective effect of 23‐HBA was shown to be closely associated with a decreased rate and extent of accumulation of doxorubicinol in mitochondria and nuclei. siRNA and docking analysis demonstrated that CBR1 has a crucial role in doxorubicin‐mediated cardiotoxicity and 23‐HBA inhibits this metabolic pathway.Conclusions and ImplicationsInhibition of CBR‐mediated doxorubicin metabolism might be one of the protective mechanisms of 23‐HBA against doxorubicin‐induced cardiotoxicity. The present study provides a new research strategy guided by pharmacokinetic theory to elucidate the mechanism of drugs with unknown targets.Linked ArticlesThis article is part of a themed section on Chinese Innovation in Cardiovascular Drug Discovery. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-23
MLN4924 sensitizes monocytes and maturing dendritic cells for TNF‐dependent and ‐independent necroptosis
Authors: El‐Mesery Mohamed , Seher Axel , Stühmer Thorsten , Siegmund Daniela , Wajant Harald 
Published: November 2014

Background and PurposeMLN4924 prevents the formation of active cullin‐RING ubiquitin ligase complexes and thus inhibits NF‐κB signalling. Here, we evaluated the effects of this compound on monocytes and dendritic cells (DCs).Experimental ApproachMonocytes and DCs were challenged with TNF or LPS in the presence and absence of MLN4924. The effects of MLN4924 on cellular viability, pro‐inflammatory gene induction and DC maturation were investigated using the MTT assay, elisa and FACS analysis. Mechanisms of cell death induction were evaluated by using inhibitors of caspases, RIPK1 and MLKL.Key ResultsMLN4924 inhibited NF‐κB activation and sensitized monocytes and immature DCs (iDCs) for TNFR1‐induced cell death. Neither the caspase inhibitor zVAD‐fmk, the RIPK1 inhibitor necrostatin‐1 (nec‐1) nor the MLKL inhibitor necrosulfonamide (NSA) alone prevented TNF‐induced cell death. A combination of zVAD‐fmk and nec‐1 or NSA, however, rescued monocytes and iDCs from MLN4924/TNF‐induced cell death indicating that MLN4924 affects anti‐apoptotic and anti‐necrotic activities in TNFR1 signalling. MLN4924 also converted the response of iDCs to LPS from maturation to cell death. LPS‐induced cell death in MLN4924‐treated iDCs was again only effectively blocked by cotreatment with zVAD‐fmk and nec‐1 or NSA. Noteworthy, MLN4924/LPS‐induced cell death was almost completely independent of endogenous TNF. MLN4924 also strongly inhibited maturation and activation of iDCs that were rescued from cell death by zVAD‐fmk and nec‐1.Conclusions and ImplicationsOur data reveal a strong dual suppressive effect of MLN4924 on DC activity. The targeting of NAE by MLN4924 could be a new way to treat inflammatory diseases.
Novel Nrf2 activators from microbial transformation products inhibit blood–retinal barrier permeability in rabbits
Authors: Nakagami Yasuhiro , Masuda Kayoko , Hatano Emiko , Inoue Tatsuya , Matsuyama Takuya , Iizuka Mayumi , Ono Yasunori , Ohnuki Takashi , Murakami Yoko , Iwasaki Masaru , Yoshida Kazuhiro , Kasuya Yuji , Komoriya Satoshi 
Published: November 2014

Background and PurposeNuclear factor erythroid 2‐related factor 2 (Nrf2) is a redox‐sensitive transcription factor that binds to antioxidant response elements located in the promoter region of genes encoding many antioxidant enzymes and phase II detoxifying enzymes. Activation of the Nrf2 pathway seems protective for many organs, and although a well‐known Nrf2 activator, bardoxolone methyl, was evaluated clinically for treating chronic kidney disease, it was found to induce adverse events. Many bardoxolone methyl derivatives, mostly derived by chemical modifications, have already been studied. However, we adopted a biotransformation technique to obtain a novel Nrf2 activator.Experimental ApproachThe potent novel Nrf2 activator, RS9, was obtained from microbial transformation products. Its Nrf2 activity was evaluated by determining NADPH:quinone oxidoreductase‐1 induction activity in Hepa1c1c7 cells. We also investigated the effects of RS9 on oxygen‐induced retinopathy in rats and glycated albumin‐induced blood–retinal barrier permeability in rabbits because many ocular diseases are associated with oxidative stress and inflammation.Key ResultsBardoxolone methyl doubled the specific activity of Nrf2 in Hepa1c1c7 cells at a much higher concentration than RS9. Moreover, the induction of Nrf2‐targeted genes was observed at a one‐tenth lower concentration of RS9. Interestingly, the cytotoxicity of RS9 was substantially reduced compared with bardoxolone methyl. Oral and intravitreal administration of RS9 ameliorated the pathological scores and leakage in the models of retinopathy in rats and ocular inflammation in rabbits respectively.Conclusion and ImplicationsNrf2 activators are applicable for treating ocular diseases and novel Nrf2 activators have potential as a unique method for prevention and treatment of retinovascular disease.
The phytocannabinoid, Δ9‐tetrahydrocannabivarin, can act through 5‐HT1A receptors to produce antipsychotic effects
Authors: Cascio Maria Grazia , Zamberletti Erica , Marini Pietro , Parolaro Daniela , Pertwee Roger G 
Published: November 2014

Background and PurposeThis study aimed to address the questions of whether Δ9‐tetrahydrocannabivarin (THCV) can (i) enhance activation of 5‐HT1A receptors in vitro and (ii) induce any apparent 5‐HT1A receptor‐mediated antipsychotic effects in vivo.Experimental ApproachIn vitro studies investigated the effect of THCV on targeting by 8‐hydroxy‐2‐(di‐n‐propylamino)tetralin (8‐OH‐DPAT) of 5‐HT1A receptors in membranes obtained from rat brainstem or human 5‐HT1A CHO cells, using [35S]‐GTPγS and 8‐[3H]‐OH‐DPAT binding assays. In vivo studies investigated whether THCV induces signs of 5‐HT1A receptor‐mediated antipsychotic effects in rats.Key ResultsTHCV (i) potently, albeit partially, displaced 8‐[3H]‐OH‐DPAT from specific binding sites in rat brainstem membranes; (ii) at 100 nM, significantly enhanced 8‐OH‐DPAT‐induced activation of receptors in these membranes; (iii) produced concentration‐related increases in 8‐[3H]‐OH‐DPAT binding to specific sites in membranes of human 5‐HT1A receptor‐transfected CHO cells; and (iv) at 100 nM, significantly enhanced 8‐OH‐DPAT‐induced activation of these human 5‐HT1A receptors. In phencyclidine‐treated rats, THCV, like clozapine (i) reduced stereotyped behaviour; (ii) decreased time spent immobile in the forced swim test; and (iii) normalized hyperlocomotor activity, social behaviour and cognitive performance. Some of these effects were counteracted by the 5‐HT1A receptor antagonist, WAY100635, or could be reproduced by the CB1 antagonist, AM251.Conclusions and ImplicationsOur findings suggest that THCV can enhance 5‐HT1A receptor activation, and that some of its apparent antipsychotic effects may depend on this enhancement. We conclude that THCV has therapeutic potential for ameliorating some of the negative, cognitive and positive symptoms of schizophrenia.
Inhibition of L‐carnitine biosynthesis and transport by methyl‐γ‐butyrobetaine decreases fatty acid oxidation and protects against myocardial infarction
Authors: Liepinsh E , Makrecka‐Kuka M , Kuka J , Vilskersts R , Makarova E , Cirule H , Loza E , Lola D , Grinberga S , Pugovics O , Kalvins I , Dambrova M 
Published: November 2014

Background and PurposeThe important pathological consequences of ischaemic heart disease arise from the detrimental effects of the accumulation of long‐chain acylcarnitines in the case of acute ischaemia‐reperfusion. The aim of this study is to test whether decreasing the L‐carnitine content represents an effective strategy to decrease accumulation of long‐chain acylcarnitines and to reduce fatty acid oxidation in order to protect the heart against acute ischaemia–reperfusion injury.Key ResultsIn this study, we used a novel compound, 4‐[ethyl(dimethyl)ammonio]butanoate (Methyl‐GBB), which inhibits γ‐butyrobetaine dioxygenase (IC50 3 μM) and organic cation transporter 2 (OCTN2, IC50 3 μM), and, in turn, decreases levels of L‐carnitine and acylcarnitines in heart tissue. Methyl‐GBB reduced both mitochondrial and peroxisomal palmitate oxidation rates by 44 and 53% respectively. In isolated hearts treated with Methyl‐GBB, uptake and oxidation rates of labelled palmitate were decreased by 40%, while glucose oxidation was increased twofold. Methyl‐GBB (5 or 20 mg·kg−1) decreased the infarct size by 45–48%. In vivo pretreatment with Methyl‐GBB (20 mg·kg−1) attenuated the infarct size by 45% and improved 24 h survival of rats by 20–30%.Conclusions and ImplicationsReduction of L‐carnitine and long‐chain acylcarnitine content by the inhibition of OCTN2 represents an effective strategy to protect the heart against ischaemia–reperfusion‐induced damage. Methyl‐GBB treatment exerted cardioprotective effects and increased survival by limiting long‐chain fatty acid oxidation and facilitating glucose metabolism.