bluuebunny/crossref_metadata_2025 huggingface dataset:
Cerebral toxoplasmosis after rituximab therapy for splenic marginal zone lymphoma: a case report and review of the literature
Authors: Holland Mary Siobhan , Sharma Karan , Lee B. Craig
Published: November 2015

Introduction:

Toxoplasma gondii is a parasite estimated to infect one-third of the global population, surviving in tissues in a latent form. Although cerebral toxoplasmosis is predominantly recognized as an opportunistic infection in hosts immunocompromised secondary to human immunodeficiency virus or bone marrow transplant, there is increasing recognition that this infection can occur in patients receiving immunomodulating agents such as mAb therapy targeted against T-cells, B-cells and TNF. The indications for these therapies are expanding, resulting in a larger at-risk population for this rare but serious and potentially avoidable complication.

Case Presentation:

This is one of the few case reports of cerebral toxoplasmosis following rituximab-based chemotherapy in a patient with a haematological malignancy. We describe a patient presenting with focal neurological deficits and radiographic evidence of multi-focal cerebral ring-enhancing lesions following completion of rituximab therapy for splenic marginal zone lymphoma. Brain biopsy confirmed a diagnosis of cerebral toxoplasmosis. Antibiotic treatment with trimethoprim/sulfamethoxazole resulted in near-complete radiological and clinical resolution of the neurological deficits, and a return to baseline functional status.

Conclusion:

Reactivation of toxoplasmosis resulting in intracerebral disease is a potential severe and preventable complication of rituximab therapy. Further studies are required to assess the need both for screening and prescribing primary chemoprophylaxis for toxoplasmosis when initiating rituximab therapy.
Incomplete protection against dengue virus type 2 re-infection in Peru
Authors: Forshey Brett M. , Reiner Robert C. , Olkowski Sandra , Morrison Amy C. , Espinoza Angelica , Long Kanya C. , Vilcarromero Stalin , Casanova Wilma , Wearing Helen J. , Halsey Eric S. , Kochel Tadeusz J. , Scott Thomas W. , Stoddard Steven T.
Published: November 2015

Background.Nearly half of the world’s population is at risk for dengue, yet no licensed vaccine or anti-viral drug is currently available. Dengue is caused by any of four dengue virus serotypes (DENV-1 through DENV-4), and infection by a DENV serotype is assumed to provide life-long protection against re-infection by that serotype. We investigated the validity of this fundamental assumption during a large dengue epidemic caused by DENV-2 in Iquitos, Peru, in 2010-2011, 15 years after the first outbreak of DENV-2 in the region.

Methodology/Principal Findings.We estimated the age-dependent prevalence of serotype-specific DENV antibodies from longitudinal cohort studies conducted between 1993 and 2010. During the 2010-2011 epidemic, active dengue cases were identified through active community- and clinic-based febrile surveillance studies, and acute inapparent DENV infections were identified through contact tracing studies. Based on the age-specific prevalence of DENV-2 neutralizing antibodies, the age distribution of DENV-2 cases was markedly older than expected. Homologous protection was estimated at 35.1% (95% confidence interval: 0% -- 65.2%). At the individual level, pre-existing DENV-2 antibodies were associated with an incomplete reduction in the frequency of symptoms. Among dengue cases, 43% (26/66) exhibited elevated DENV-2 neutralizing antibody titers for years prior to infection, compared with 76% (13/17) of inapparent infections (age-adjusted odds ratio: 4.2; 95% confidence interval: 1.1 – 17.7).

Conclusions/Significance.Our data indicate that protection from homologous DENV re-infection may be incomplete in some circumstances, which provides context for the limited vaccine efficacy against DENV-2 in recent trials. Further studies are warranted to confirm this phenomenon and to evaluate the potential role of incomplete homologous protection in DENV transmission dynamics.

Author Summary

Homotypic immunity against DENV infection has been assumed to be complete and lifelong, and to our knowledge, instances of homologous DENV re-infection have not been rigorously documented. However, few long-term studies have been conducted in such a way that homologous re-infection could be observed, if it did in fact occur. Our study provides evidence that homologous re-infection may occur in certain circumstances. We draw from data collected during a 2010-2011 DENV-2 epidemic in northeastern Peru, 15 years after the initial DENV-2 outbreak in the region. This finding has significant implications for our understanding of dengue epidemiology and for dengue vaccine formulation, which may need to consider multiple genotypes of each serotype. Data from other long-term dengue epidemiology studies should be analyzed to determine of homologous re-infection is a more widespread phenomenon.
Serial commitments clearance in Rastin Banking
Authors: Bidabad Bijan
Published: November 2015

Purpose

– This paper aims to propose a system for settlement of obligations of those who, on the one hand, serially owe someone and, on the other hand, are creditors to other persons. Serial Commitments Clearance (SCC) system provides the necessary arrangements for this purpose.

Design/methodology/approach

– Theoretical discussions of serial chain of debits and credits were conducted by considering the laws and regulations of commitment clearance.

Findings

– By considering laws and regulations of commitment clearance and introducing theory of serial chain of debits and credits, this system proposes an algorithm for recognition of serial commitments.

Research limitations/implications

– This process is set in connection to the Collateral Registration System and Mortgage Securitization System in Rastin Banking, while considering the legal and operational problems. Accordingly, banks, notary offices and other authorized authorities can clear serial obligations of persons due to their requests and agreements and release their collaterals and guarantees as far as the debts of the persons are equivalent.

Practical implications

– This system will cause financial release and efficiency of many economic firms. In addition, banks will gain commission for rendering this service.

Social implications

– SCC is a model that can be used in all countries, especially those which have more uncertainties and traders need more pledges for their transactions.

Originality/value

– This study fulfils an identified need to solve practical legal problems in vindication of rights.
Remuneration consultants: benchmarking and its effect on pay
Authors: Ndzi Ernestine
Published: November 2015

Purpose

– The purpose of this paper is to investigate the factors that remuneration consultants consider when selecting comparator groups for executive remuneration benchmarking. It explores how the different factors influence the level of pay and whether the factors encourage pay-for-performance. Furthermore, it investigates whether the factors used form part of the reasons why remuneration consultants have been criticised to be correlated with high executive pay.

Design/methodology/approach

– This paper analysis the data obtained from interviewing remuneration consultants from prominent consultancy firms that operate in the UK and the USA.

Findings

– This paper demonstrates that there is no uniformity in the factors used by remuneration consultants when selecting comparator groups for executive remuneration benchmarking. The paper shows that company performance is not a major factor considered justifying why executive pay is not linked to company performance. The paper further demonstrates that the factors that remuneration consultants consider in selecting comparator groups for executive remuneration benchmarking justify high pay and affirm that remuneration consultants are associated with high pay.

Originality/value

– This paper demonstrates the effect that lack of best practice on benchmarking is partly responsible for the high executive pay levels and the weak link between pay and performance. This paper will inform companies on what to demand from remuneration consultants when hiring their services. Second, it will provide the shareholders with vital information that they need to vote on remuneration reports in the annual general meeting. Finally, it informs policy makers on the grey areas of practice that require best practice.
Regulation compliance in small Finnish companies
Authors: Sjögrén Helena , Syrjä Pasi
Published: November 2015

Purpose

– The purpose of this paper is to learn more about how regulation affects small business in the Finnish context. The authors create a framework for understanding owner-managers’ attitudes towards business legislation. It is authors’ understanding that not enough is known about how small firms make strategic choices that drive business in a highly regulated environment.

Design/methodology/approach

– This paper contributes to the existing knowledge of entrepreneurship and small business management. The empirical data used to test the hypotheses were drawn from the postal survey. Differences between owner-managers’ attitudes towards business regulation were identified with factor and cluster analyses methods.

Findings

– Regulation often exerts only a limited influence over owner-managers’ decision-making. Family entrepreneurs are more compliant towards business regulation. Regulation is not too heavy a burden to all in business in Finland, even though Finland is a highly regulated country.

Research limitations/implications

– The real impact of regulation on small firms’ performance is really difficult to prove, because small firms operating in the same regulatory context have different performance outcomes. Additionally, often owner-managers’ awareness of specific regulations is limited.

Practical implications

– There could be gap between the presumed effect of policymakers and the real effect of regulation among owner-managers. In Finland, policymakers should find other motivations to encourage business than lightening the regulatory burden. They should concentrate more providing external support to small firms in the form of information, training and financing new small firms.

Originality/value

– It is authors’ understanding that not enough is known about how small firms make strategic choices that drive business in a highly regulated environment.
Influence of the principle of interoperability on legal regulation
Authors: Zharova Anna
Published: November 2015

Purpose

– The purpose of this paper is to identify the legal problems connected with using the systems of technological interoperability in the society.

Design/methodology/approach

– In the paper, the compared-legal method was applied. The legislation of Russia and that of European Union (EU) have been compared.

Findings

– Generalizing about the problems identified in both Russia and the EU, it is possible to conclude that: States have to develop a coordinated, uniform security policy. Public administrations have to implement interoperable services for business and citizens. States have to introduce the required standards. It is necessary to forbid development or creation of any departmental technical specifications by public institutions or departments which are not coordinated with the larger transnational goals.

Originality/value

– In the paper, the problems that arise in the states (Russia and EU) if they did not take into account the principle of interoperability are revealed. Legal mechanisms directed on permission of arising problems are described.
Mutual gains or conflicting outcomes? How HRM benefits professionals
Authors: Edgar Fiona , Geare Alan , Zhang Jing A. , McAndrew Ian
Published: November 2015

Purpose

– Using the mutual gains model as a framework, the purpose of this paper is to explore the important issue of mutuality in employment relationships.

Design/methodology/approach

– This study uses a sample of 215 New Zealand professionals to assess the relationships between commitment-oriented HRM practice, work intensification, work-life balance (WLB) and task and contextual performance.

Findings

– The authors find commitment-oriented HRM practice does not intensify the work experiences of professionals, but nor does it contribute positively to the achievement of WLB. Both these well-being types do, however, contribute to explaining professionals’ task and contextual performance outcomes.

Research limitations/implications

– The findings suggest current narrow interpretations of well-being need to be revisited, with the meaning of well-being, its measurement and its role in delivering performance outcomes afforded greater attention within HRM studies.

Practical implications

– A primary goal of managers is to deliver optimum performance outcomes. For professionals, the research suggests an important means to achieving this is by promoting positive well-being.

Originality/value

– This study offers some important insights into the role mutuality plays in influencing performance outcomes. In addition, by exploring two contrasting facets of well-being, one health- and one happiness-related, the authors provide some empirical insights into how employees’ well-being affects performance outcomes.
Management control for gender mainstreaming – a quest of transformative norm breaking
Authors: Wittbom Eva Elisabeth
Published: November 2015

Purpose

– This paper aims to discuss the gendered dimensions of management control. Gender mainstreaming is a worldwide strategy for gender equality. The question raised in this paper is how a management control system functions under the pressure of mainstreaming gender into a core business.

Design/methodology/approach

– The evidence stems from a case study at two Swedish Governmental public transport administrations. Interviews, observations of meetings and close reading of documents furnish this paper with data over a five-year period regarding the management control of the policy goal of a gender-equal transport system. The practice of management control for gender mainstreaming is studied by adopting sociological institutional theory and a gender perspective.

Findings

– The management control system proves to hamper gender equality. In a technocratic core business, the control system fails to support gender mainstreaming. In this paper, the control of a gender-equal transport system results in a quantitative perspective on women and men instead of a qualitative gender perspective on the transport system.

Practical implications

– This paper has practical implications both for accountants being involved in management control for gender mainstreaming and for all persons involved in promoting gender mainstreaming.

Originality/value

– The paper contributes to the scarce literature from research with a gender perspective on management control systems. Being exposed to gender mainstreaming, the gender perspective discloses dysfunctional dimensions within the management control system.
Review of factors constraining the development of Indian corporate bond markets
Authors: Thukral Shagun , Sridhar Sharada , Joshi Medha Shriram
Published: November 2015

Purpose

– The paper aims to understand the factors that have limited the development of this market in India. With a conservative bank-based economy in the backdrop and with the Central Bank pulling the strings, the sovereign debt market occupies the most space in the bonds universe of India. The latter and almost minuscule portion of this market is occupied by the corporate and industrial houses that have forayed into the market to raise finances. This has led to a cycle where lack of participation leads to lack of liquidity and underdeveloped rating mechanisms which further pressurizes the development of this market in India.

Design/methodology/approach

– The paper is designed as a literature review which has attempted to identify the commonly agreed upon factors that have constrained the development of Corporate Bond markets in India especially and some other emerging economies who are successful or unsuccessful in their attempt to establish a corporate bond markets. These factors have then been categorized into broader heads and commented upon as a part of the analysis.

Findings

– Corporate bond markets in India, although steadily progressing, is still impeded by the nature of the market itself. While the necessary steps have been taken to implement some of the recommendations by the Expert Committee, the response solicited has not quite been as expected. The poor liquidity, weak rating-mechanisms, absence of standardization and disclosure nomenclatures and illiquidity in the government bond market itself need to be addressed objectively.

Research limitations/implications

– The research adopted attempts to validate prior research and the attempts by regulators to implement an action plan. However, further progress on the changing scenarios is encouraged to be tested through a quantitative analysis.

Originality/value

– The government and the Central Bank have constantly emphasized the importance of developing the Corporate debt market. Several studies have attempted to analyze the factors that have crippled the growth and steps taken by the Central Bank and Securities and Exchange Board of India by appointing an Expert Committee. This paper has attempted to visit all these factors and analyze the attempts to overcome by the Expert Committee including the backdrop of other nations who have a vibrant corporate debt market today. It sets the tone for further quantitative or statistical analysis.
Ownership as a determinant of chairperson activity: a study of Nordic listed companies
Authors: Brunzell Tor , Peltomäki Jarkko
Published: November 2015

Purpose

– The purpose of this study is to explicitly focus on the roles of ownership concentration, ownership by the board, the chief executive officer (CEO) and the chairperson in the involvement and capabilities of chairpersons and other governors in their work.

Design/methodology/approach

– In this study, the authors investigate the impact of the concentration of ownership, the ownership of the board, the CEO and the chairperson on the chairperson’s activity when the roles of the chairperson and the CEO are separated The empirical analysis of this study is based on a survey sent to Nordic listed firms.

Findings

– The results show that the ownership characteristics of a company are important in determining the chairperson’s working hours, the chairperson’s communication with the CEO and the performance of governance activity. In addition, the authors found that while the ownership of the chairperson and the board of directors and ownership concentration improve governance activity, CEO ownership may undermine governance activity.

Research limitations/implications

– The primary implication of the study is that both ownership by internal governors and ownership concentration play an important role in determining the involvement of internal corporate governors.

Originality/value

– The study provides unique evidence that ownership by the chairperson, concentrated ownership and ownership by the board can potentially mitigate the costs of separating the roles of the chairperson and the CEO.
When can positive interactions cause alternative stable states in ecosystems?
Authors: Kéfi Sonia , Holmgren Milena , Scheffer Marten
Published: November 2015

After a period of heavy emphasis on negative interactions, such as predation and competition, the past two decades have seen an explosion of literature on the role of positive interactions in ecological communities. Such positive interactions can take many forms. One possibility is that amelioration of environmental stress by plants or sessile animals enhances growth, reproduction and survival of others, but many more intricate patterns exist.

Importantly such positive interactions may contribute to creating a positive feedback. For instance, biomass can lead to improved environmental conditions causing better growth and therefore leading to more biomass. A positive feedback is a necessary (but not sufficient) condition for the emergence of alternative stable states at the community scale. However, the literature on positive interactions in plant and animal communities rarely addresses this connection.

Here, we address this gap, asking the question of when positive interactions may lead to alternative stable states, and hence set the stage for catastrophic transitions at tipping points in ecosystems. We argue that, although there are a number of now classical examples in the literature for which positive interactions are clearly the main actors of positive feedback loops, more empirical and theoretical research scaling up from the individual‐level interactions to the community and the ecosystem scale processes is needed to further understand under which conditions positive interactions can trigger positive feedback loops, and thereby alternative stable states.
PANSS‐6: a brief rating scale for the measurement of severity in schizophrenia
Authors: Østergaard S. D. , Lemming O. M. , Mors O. , Correll C. U. , Bech P.
Published: November 2015

Objective

The 30‐item Positive and Negative Syndrome Scale (PANSS‐30) is the most widely used rating scale in schizophrenia, but too long for clinical use. Shorter PANSS versions have been proposed, including the PANSS‐14 and PANSS‐8. However, none of these PANSS versions has been validated using the parametric Rasch rating scale model, which evaluates ‘scalability’. Scalability means that each item in a rating scale provides unique information regarding syndrome severity and is a statistical prerequisite for using the total score as a measure of overall severity.

Method

Based on data from two randomized placebo‐controlled trials in schizophrenia, we tested the scalability of PANSS‐30, PANSS‐14 and PANSS‐8 by means of the parametric Rasch rating scale model. Furthermore, we tested whether a scalable PANSS version could separate efficacy of haloperidol and sertindole from placebo.

Results

Neither PANSS‐30, PANSS‐14 nor PANSS‐8 was scalable. However, PANSS‐6, consisting of the items: P1‐Delusions, P2‐Conceptual disorganization, P3‐Hallucinations, N1‐Blunted Affect, N4‐Social withdrawal, N6‐Lack of spontaneity and flow of conversation, was scalable. Furthermore, PANSS‐6 captured superior symptom reduction and higher remission rates during treatment with haloperidol and sertindole vs. placebo.

Conclusion

PANSS‐6 is a short schizophrenia severity rating scale that adequately separates antipsychotic efficacy from that of placebo.
Sites of Liberation or Sites of Despair?: The Challenges and Possibilities of Democratic Education in an Urban Public School in New York City
Authors: Hantzopoulos Maria
Published: November 2015

This article considers the possibilities of critical democratic education through the lived experiences of students at an urban U.S. public school. I show how students shape their own educational trajectories amid larger meta‐narratives about schooling to illuminate the complexities and paradoxes of democratic schools. I argue that democratic schools are neither sites of transformation nor sites of despair, but rather sites where agency is negotiated, contested, and remade, often in unexpected, unassuming, and contradictory ways.
“Denial or Faith?” Therapy Versus Messianism in Preparing for the Evacuation of Israeli Settlements
Authors: Plotkin Amrami Galia
Published: November 2015

This article offers an ethnographic account of the professional activities of mental health practitioners, employed by the state's religious education system. I analyze various models implemented by practitioners for the purposes of preparing pupils for the state‐mandated evacuation of Jewish settlers from Gaza and the West Bank. By focusing on the interaction between psychological and religious‐national cultural frameworks I show how practitioners imbue familiar professional concepts with new meanings and create hybrid models of intervention.
Implementation of the WHO Surgical Safety Checklist and surgical swab and instrument counts at a regional referral hospital in Uganda – a quality improvement project
Authors: Lilaonitkul M. , Kwikiriza A. , Ttendo S. , Kiwanuka J. , Munyarungero E. , Walker I. A. , Rooney K. D.
Published: November 2015

The World Health Organization (WHO) Surgical Safety Checklist is a cost‐effective tool that has been shown to improve patient safety. We explored the applicability and effectiveness of quality improvement methodology to implement the WHO checklist and surgical counts at Mbarara Regional Referral Hospital in Uganda between October 2012 and September 2013. Compliance rates were evaluated prospectively and monthly structured feedback sessions were held. Checklist and surgical count compliance rates increased from a baseline median (IQR [range]) of 29.5% (0–63.5 [0–67.0]) to 85.0% (82.8–87.5 [79.0–93.0]) and from 25.5% (0–52.5 [0–60.0]) to 83.0% (80.8–85.5 [69.0–89.0]), respectively. The mean all‐or‐none completion rate of the checklist was 69.3% (SD 7.7, 95% CI [64.8–73.9]). Use of the checklist was associated with performance of surgical counts (p value < 0.001; r2 = 0.91). Pareto analysis showed that understaffing, malfunctioning and lack of equipment were the main challenges. A carefully designed quality improvement project, including stepwise incremental change and standardisation of practice, can be an effective way of improving clinical practice in low‐income settings.
Critical care after lung resection: CALoR 1, a single‐centre pilot study
Authors: McCall P. J. , Macfie A. , Kinsella J. , Shelley B. G.
Published: November 2015

Lung resection is associated with significant perioperative morbidity, and a proportion of patients will require intensive care following surgery. We set out to characterise this population, assess their burden of disease and investigate the influence of anaesthetic and surgical techniques on their admission rate. Over a two‐year period, 1169 patients underwent surgery, with 30 patients (2.6%) requiring unplanned intensive care. Patients requiring support had a higher mortality (0.2% vs 26.7%, p < 0.001). Logistic regression (following adjustment for Thoracoscore) revealed that an open surgical approach was associated with higher likelihood of admission (p = 0.025, odds ratio = 5.25). There was also a trend towards increased likelihood of admission in patients who received volatile anaesthesia (p = 0.061, odds ratio = 2.08). This topic has been selected for further investigation as part of the 2015 Association of Cardiothoracic Anaesthetists (ACTA) second national collaborative audit, with this study providing pilot data before a multi‐centre study.
Randomised clinical trial: vonoprazan, a novel potassium‐competitive acid blocker, vs. lansoprazole for the healing of erosive oesophagitis
Authors: Ashida K. , Sakurai Y. , Hori T. , Kudou K. , Nishimura A. , Hiramatsu N. , Umegaki E. , Iwakiri K.
Published: November 2015

Background

Vonoprazan is a novel potassium‐competitive acid blocker which may provide clinical benefit in acid‐related disorders.

Aim

To verify the non‐inferiority of vonoprazan vs. lansoprazole in patients with erosive oesophagitis (EE), and to establish its long‐term safety and efficacy as maintenance therapy.

Methods

In this multicentre, randomised, double‐blind, parallel‐group comparison study, patients with endoscopically confirmed EE (LA Classification Grades A–D) were randomly allocated to receive vonoprazan 20 mg or lansoprazole 30 mg once daily after breakfast. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy up to week 8. In addition, subjects who achieved healed EE in the comparison study were re‐randomised into a long‐term study to investigate the safety and efficacy of vonoprazan 10 or 20 mg as maintenance therapy for 52 weeks.

Results

Of the 409 eligible subjects randomised, 401 completed the comparison study, and 305 entered the long‐term maintenance study. The proportion of patients with healed EE up to week 8 was 99.0% for vonoprazan (203/205) and 95.5% for lansoprazole (190/199), thus verifying the non‐inferiority of vonoprazan (P < 0.0001). Vonoprazan was also effective in patients with more severe EE (LA Classification Grades C/D) and CYP2C19 extensive metabolisers. In the long‐term maintenance study, there were few recurrences (<10%) of EE in patients treated with vonoprazan 10 or 20 mg. Overall, vonoprazan was well‐tolerated.

Conclusions

The non‐inferiority of vonoprazan to lansoprazole in EE was verified in the comparison study, and vonoprazan was well‐tolerated and effective during the long‐term maintenance study.
Combined ursodeoxycholic acid (UDCA) and fenofibrate in primary biliary cholangitis patients with incompleteUDCAresponse may improve outcomes
Authors: Cheung A. C. , Lapointe‐Shaw L. , Kowgier M. , Meza‐Cardona J. , Hirschfield G. M. , Janssen H. L. A. , Feld J. J.
Published: November 2015

Background

Fibrates appear to improve biochemistry in patients with primary biliary cholangitis (PBC), but it is unclear which factors predict response and whether treatment improves transplant‐free survival.

Aim

To evaluate biochemical profiles, liver‐related outcomes and adverse events following fenofibrate therapy inPBCpatients with incomplete response to ursodeoxycholic acid (UDCA).

Methods

A retrospective cohort study was performed at a tertiary centre. Cox regression was used to compare outcomes between patients treated with fibrates andUDCA(FF) orUDCAalone, adjusted for a propensity score to account for treatment selection bias.

Results

A total of 120 patients were included (FFgroupn= 46,UDCAgroupn= 74, median fenofibrate treatment 11 months); 41% vs. 7% met the Toronto criteria for biochemical response [alkaline phosphatase ≤1.67 times the upper limit of normal] in theFFandUDCAgroups, respectively (P= 0.0001). Fenofibrate was also associated with improved decompensation‐free and transplant‐free survival [hazard ratio (HR) 0.09, 95%CI0.03–0.32,P= 0.0002]. However, only fenofibrate use, not biochemical response, was independently associated with improved outcomes on multivariable analysis (HR0.40, 95%CI0.17–0.93,P= 0.03). Twenty‐two percent discontinued fenofibrate due to adverse events (most common: abdominal pain and myalgias). In cirrhotic patients, bilirubin increased more rapidly in theFFgroup (P= 0.005).

Conclusions

Fenofibrate therapy is associated with significant improvement inalkaline phosphatase, decompensation‐free and transplant‐free survival inPBCpatients with incompleteUDCAresponse. However, fenofibrate should be used cautiously in cirrhosis, with close monitoring for clinical/biochemical decompensation. Additional studies are required to assess the validity ofalkaline phosphataseas an appropriate response criteria for fibrate therapy.
Expression of Forkhead box M1 in soft tissue leiomyosarcoma: Clinicopathologic and in vitro study using a newly established cell line
Authors: Maekawa Akira , Kohashi Kenichi , Setsu Nokitaka , Kuda Masaaki , Iura Kunio , Ishii Takeaki , Matsunobu Tomoya , Nakatsura Tetsuya , Iwamoto Yukihide , Oda Yoshinao
Published: November 2015

Leiomyosarcoma (LMS) of soft tissue is a sarcoma with smooth‐muscle differentiation, and conventional chemotherapy does not improve its outcome. The application of novel antitumor agents and precise prognostication has been demanded. The expression of the protein Forkhead box M1 (FOXM1), a member of the FOX family, is considered an independent predictor of poor survival in many cancers and sarcomas. However, the expression status of FOXM1 in LMS is poorly understood. The purposes of this study were to examine the correlation between the expression of FOXM1 and clinicopathologic or prognostic factors and to clarify the efficacy of FOXM1 target therapy in LMS. We evaluated the immunohistochemical expressions of FOXM1 using 123 LMS tumor specimens. Univariate and multivariate survival analyses revealed that FOXM1 expression was associated with poor prognosis in LMS. An in vitro study was then carried out to examine the antitumor effect of a FOXM1 inhibitor (thiostrepton) and siRNA on a novel LMS cell line, TC616. We also assessed the efficacy of the combined use of doxorubicin and thiostrepton. Thiostrepton showed dose‐dependent antitumor activity and TC616 cells treated with the combination of thiostrepton and doxorubicin showed lower proliferation compared to those treated with either drug individually. FOXM1 interruption by siRNA decreased cell proliferation and increased chemosensitivity. In conclusion, FOXM1 has potential to be a therapeutic target for LMS.
Contact allergy to chlorhexidine in a tertiary dermatology clinic in Denmark
Authors: Opstrup Morten S. , Johansen Jeanne D. , Zachariae Claus , Garvey Lene H.
Published: November 2015

Background

Chlorhexidine is a widely used disinfectant in the healthcare setting and in cosmetic products. A high prevalence of chlorhexidine contact allergy was reported in Denmark in the 1980s (2.0–5.4% of patients patch tested). It is unknown whether the prevalence is still high, which products cause the contact allergy, and whether accidental re‐exposure occurs in some patients.

Objectives

To estimate the prevalence of chlorhexidine contact allergy in a tertiary dermatology clinic in Denmark; to investigate whether patch testing with both chlorhexidine diacetate and chlorhexidine digluconate is necessary; to investigate how many patients have combined immediate‐type allergy and contact allergy; and to identify which products cause chlorhexidine contact allergy, and whether patients are accidentally re‐exposed.

Methods

This was a retrospective study including all patients patch tested with chlorhexidine during 2003–2013 at the Department of Dermato‐Allergology at Copenhagen University Hospital Gentofte (n = 8497). All patients with a positive patch test reaction to chlorhexidine were sent a questionnaire comprising questions about the cause of the allergy and re‐exposure.

Results

Overall, 1.0% (n = 82) of all patients patch tested with chlorhexidine were positive. A decrease in the prevalence was observed over time, most likely because of lowering of the test concentration from 1.0 to 0.5% in 2008. Of the 82 patients, 28 (0.3%) had positive test reactions to both chlorhexidine salts, 43 (0.5%) had a positive test reaction only to chlorhexidine diacetate, and 11 (0.1%) had a positive test reaction to chlorhexidine digluconate. Three patients were both patch test‐positive and prick test‐positive. A known cause of the allergy was reported by 19 patients (40%) in the questionnaire: the products used in the healthcare setting were mainly reported, but some reported cosmetic products. Accidental re‐exposure was reported by 15 patients (32%), of whom 13 reported symptoms.

Conclusions

The prevalence of chlorhexidine contact allergy does not seem to be higher in Denmark than in other European countries. Patch testing with both chlorhexidine diacetate and chlorhexidine digluconate may be beneficial. Testing for immediate‐type allergy in patients with a positive patch test reaction to chlorhexidine is recommended. Chlorhexidine‐containing products used in the healthcare setting and in cosmetics are potential causes of sensitization and allergy. Re‐exposure is common, highlighting the fact that patients and healthcare personnel need to be well informed about possible sources of exposure.
In vitro comparison of the effect of two factor XI (FXI) concentrates on thrombin generation in major FXI deficiency
Authors: Pike G. N. , Cumming A. M. , Hay C. R. M. , Sempasa B. , Sutherland M. , Thachil J. , Burthem J. , Bolton‐Maggs P. H. B.
Published: November 2015

Introduction

Bleeding risk in factor XI (FXI) deficiency following surgery may be reduced by treatment with either of two FXI concentrates, but indications for their use are unclear and treatment has been associated with thrombosis.

Aim

To quantify and compare the effects of two different FXI concentrates on thrombin generation (TG) in major FXI deficiency (FXI:C < 15 IU dL−1).

Methods

Thrombin generation was measured in controls (n = 50), FXI‐deficient individuals pre and post in vitro spiking with FXI concentrates (n = 10), and in ex vivo samples following treatment with FXI concentrate (n = 3).

Results

Thrombin generation was significantly impaired in FXI deficiency but improved following FXI replacement in vitro and in vivo. LFB Hemoleven® had greater effect on TG than BPL FXI concentrate in vitro (equivalent in vivo doses 10, 20 and 30 U kg−1): higher endogenous thrombin potential (ETP) (P < 0.0001), peak height (P < 0.01) velocity (P < 0.0002) and shorter lag time and time to peak (both P < 0.003). Some measurements with LFB Hemoleven® exceeded the reference range. At lower dose (5 U kg−1), BPL FXI concentrate normalized all TG parameters and LFB Hemoleven® normalized the ETP but exceeded the reference range with other parameters.

Conclusion

Both FXI concentrates improve TG in vitro in major FXI deficiency but differ in dose response, and for both products, doses lower than previously recommended normalized TG in vitro. Comparison of in vitro spiked and ex vivo samples suggest that in vitro results could be used to estimate an expected in vivo response to FXI replacement.
A wearable wound moisture sensor as an indicator for wound dressing change: an observational study of wound moisture and status
Authors: Milne Stephen D , Seoudi Ihab , Al Hamad Hanadi , Talal Talal K , Anoop Anzila A , Allahverdi Niloofar , Zakaria Zain , Menzies Robert , Connolly Patricia
Published: November 2015

Wound moisture is known to be a key parameter to ensure optimum healing conditions in wound care. This study tests the moisture content of wounds in normal practice in order to observe the moisture condition of the wound at the point of dressing change. This study is also the first large‐scale observational study that investigates wound moisture status at dressing change. The WoundSense sensor is a commercially available moisture sensor which sits directly on the wound in order to find the moisture status of the wound without disturbing or removing the dressing. The results show that of the 588 dressing changes recorded, 44·9% were made when the moisture reading was in the optimum moisture zone. Of the 30 patients recruited for this study, 11 patients had an optimum moisture reading for at least 50% of the measurements before dressing change. These results suggest that a large number of unnecessary dressing changes are being made. This is a significant finding of the study as it suggests that the protocols currently followed can be modified to allow fewer dressing changes and less disturbance of the healing wound bed.
Advance care planning for nursing home residents with dementia: policy vs. practice
Authors: Ampe Sophie , Sevenants Aline , Smets Tinne , Declercq Anja , Van Audenhove Chantal
Published: November 2015

Aims

The aims of this study were: to evaluate the advance care planning policy for people with dementia in nursing homes; to gain insight in the involvement of residents with dementia and their families in advance care planning, and in the relationship between the policy and the actual practice of advance care planning.

Background

Through advance care planning, nursing home residents with dementia are involved in care decisions, anticipating their reduced decision‐making capacity. However, advance care planning is rarely realized for this group. Prevalence and outcomes have been researched, but hardly any research has focused on the involvement of residents/families in advance care planning.

Design

Observational cross‐sectional study in 20 nursing homes.

Methods

The ACP audit assessed the views of the nursing homes’ staff on the advance care planning policy. In addition, individual conversations were analysed with ‘ACP criteria’ (realization of advance care planning) and the ‘OPTION’ instrument (involvement of residents/families). Data collection: June 2013–September 2013.

Results

Nursing homes generally met three quarters of the pre‐defined criteria for advance care planning policy. In almost half of the conversations, advance care planning was explained and discussed substantively. Generally, healthcare professionals only managed to involve residents/families on a baseline skill level. There were no statistically significant correlations between policy and practice.

Conclusion

The evaluations of the policy were promising, but the actual practice needs improvement. Future assessment of both policy and practice is recommended. Further research should focus on communication interventions for implementing advance care planning in the daily practice.
Soil microorganisms behave like macroscopic organisms: patterns in the global distribution of soil euglyphid testate amoebae
Authors: Lara Enrique , Roussel‐Delif Ludovic , Fournier Bertrand , Wilkinson David M. , Mitchell Edward A. D.
Published: November 2015

Aim

Patterns of α‐ and β‐diversity of soil protist communities and the factors that shape them remain largely unknown. We undertook a world‐wide survey of forest litter to investigate the patterns of diversity in a group of testate amoebae. We aimed to assess: (1) whether there is a latitudinal gradient in α‐diversity, and (2) whether β‐diversity was correlated solely with environmental factors commonly used in soil biology research or if it was also independently explained by geographical barriers.

Location

World‐wide.

Methods

We studied the diversity of Euglyphida, a common group of testate amoebae, in 35 samples of forest litter and moss samples from a global survey, using small subunit rRNA gene sequences. We assessed the relationship between sample α‐diversity and latitude using generalized additive models (GAM). Furthermore, we determined the relationships between community composition and geographical models (distance‐based Moran's Eigenvector Maps – db‐MEM) using Generalized UniFrac distances (GUniFrac). We also investigated the relationship between individual measured soil parameters, WorldClim data and diversity (alpha plus beta) using both raw data and synthetic variables obtained through principal components analysis.

Results

We recorded 245 phylotypes belonging to 6 out of 7 known Euglyphida families, plus four novel deep clades. Euglyphid α‐diversity was positively correlated with temperature and negatively with latitude and litter C/N ratio. Euglyphida community structure was correlated with the spatial eigenvector Db‐MEM31, independently of all measured environmental variables. Db‐MEM31 corresponds to a natural barrier constituted by the Northern Hemisphere desert belt. Beta diversity was correlated with other environmental variables, such as pH, isothermality and temperature in the coldest month of the year.

Main conclusions

Soil euglyphid α‐diversity displays a latitudinal gradient, and β‐diversity is not only correlated with climatic and physicochemical parameters but also with geographical barriers. Such patterns of diversity were until recently believed to be characteristic only for macroscopic organisms.
Oestradiol Exposure Early in Life Programs Daily and Circadian Activity Rhythms in Adult Mice
Authors: Royston S. E. , Bunick D. , Mahoney M. M.
Published: November 2015

Hormone signalling during critical periods organises the adult circadian timekeeping system by altering adult hormone sensitivity and shaping fundamental properties of circadian rhythmicity. However, the timing of when developmental oestrogens modify the timekeeping system is poorly understood. To test the hypothesis that alterations in postnatal oestrogenic signalling organise adult daily activity rhythms, we utilised aromatase knockout mice (ArKO), which lack the enzyme required for oestradiol synthesis. ArKO and wild‐type (WT) males and females were administered either oestradiol (E) or oil (OIL) daily for the first 5 postnatal days (p1–5E and p1–5OIL, respectively) because this time encompasses the emergence of clock gene rhythmicity and light responsiveness in the suprachiasmatic nucleus, a bilateral hypothalamic structure regarded as the ‘master oscillator’. After sexual maturation, gonadectomy and exogenous oestradiol supplementation, locomotor parameters were assessed. We determined that altered oestrogenic signalling in early life exerts organisational control over the expression of daily and circadian activity rhythms in adult mice. Specifically, p1–5E reduced total wheel running activity in male and female ArKO and female WT mice but had no effect on WT male activity levels. In females, wheel running was consolidated by p1–5E to the early versus late evening, a phenomenon characteristic of male mice. The time of peak activity was advanced by p1–5E in WT and ArKO females but not males. P1–5E shortened the length of the active phase (alpha) in WT males but had no effect on ArKO males or females of either genotypes. Finally, p1–5E altered the magnitude of photic‐induced shifts, suggesting that developmental oestrogenic signalling impacts adult circadian functions. In the present study, we further define both a critical period of development of the adult timekeeping system and the role that oestrogenic signalling plays in the expression of daily and circadian activity rhythms throughout life.
Testosterone Concentrations and Cardiovascular Autonomic Neuropathy in Men with Type 1 Diabetes in the Epidemiology of Diabetes Interventions and Complications Study (EDIC)
Authors: Kim Catherine , Pop-Busui Rodica , Braffett Barbara , Cleary Patricia A. , Bebu Ionut , Wessells Hunter , Orchard Trevor , Sarma Aruna V.
Published: November 2015

Introduction

Previous studies have reported that lower testosterone concentrations are associated with cardiovascular autonomic neuropathy (CAN), a risk factor for cardiovascular events. However, no studies have examined this relationship in men with type 1 diabetes, who are at high risk for CAN.

Aim

The aim of this study was to examine the associations between testosterone concentrations and measures of CAN in a large, well-characterized cohort of men with type 1 diabetes.

Methods

We conducted an analysis of men in the Diabetes Control and Complications Trial (DCCT), a randomized trial of intensive glucose control, and its observational follow-up the Epidemiology of Diabetes Intervention and Complications (EDIC) Study. Testosterone was measured by liquid chromatography mass spectrometry in stored samples from EDIC follow-up years 10 and 17. Regression models were used to assess the cross-sectional relationships between testosterone and CAN measures.

Main Outcome Measures

The main CAN measure from EDIC follow-up year 17 was a standardized composite of R–R variation with paced breathing < 15, or R–R variation 15–20 combined with either a Valsalva ratio ≤ 1.5 or a decrease in diastolic blood pressure > 10 mm Hg upon standing. Continuous R–R variation and Valsalva ratio were secondary outcomes.

Results

Lower total and bioavailable testosterone concentrations at follow-up years 10 and 17 were not associated with the presence of CAN at year 17. In analyses using Valsalva ratio as a continuous measure, higher total (P = 0.01) and bioavailable testosterone concentrations (P = 0.005) were associated with a higher (more favorable) Valsalva ratio after adjustment for covariates including age, body mass index, smoking status, hypertension, and glycemia.

Conclusions

Testosterone levels are not associated with CAN among men with type 1 diabetes. Although testosterone is associated with a higher Valsalva ratio, a more favorable indicator, the clinical significance of this association is not known.