bluuebunny/crossref_metadata_2025_split huggingface dataset:
Junior doctor‐led ‘near‐peer’ prescribing education for medical students
Authors: Gibson Kyle R. , Qureshi Zeshan U. , Ross Michael T. , Maxwell Simon R. 
Published: April 2013

AimsPrescribing errors are common and inadequate preparation of prescribers appears to contribute. A junior doctor‐led prescribing tutorial programme has been developed for Edinburgh final year medical students to increase exposure to common prescribing tasks. The aim of this study was to assess the impact of these tutorials on students and tutors.MethodsOne hundred and ninety‐six tutorials were delivered to 183 students during 2010–2011. Each student completed a questionnaire after tutorial attendance which explored their previous prescribing experiences and the perceived benefits of tutorial attendance. Tutors completed a questionnaire which evaluated their teaching experiences and the impact on their prescribing practice. Student tutorial attendance was compared with end‐of‐year examination performance using linear regression analysis.ResultsThe students reported increased confidence in their prescribing knowledge and skills after attending tutorials. Students who attended more tutorials also tended to perform better in end‐of‐year examinations (Drug prescribing: r = 0.16, P = 0.015; Fluid prescribing: r = 0.18, P = 0.007). Tutors considered that participation enhanced their own prescribing knowledge and skills. Although they were occasionally unable to address student uncertainties, 80% of tutors reported frequently correcting misconceptions and deficits in student knowledge. Ninety‐five percent of students expressed a preference for prescribing training delivered by junior doctors over more senior doctors.ConclusionsA ‘near‐peer’ junior doctor‐led approach to delivering prescribing training to medical students was highly valued by both students and tutors. Although junior doctors have relatively less clinical experience of prescribing, we believe that this can be addressed by training and academic supervision and is outweighed by the benefits of these tutorials.
Incidence and risk of hypertension with a novel multi‐targeted kinase inhibitor axitinib in cancer patients: a systematic review and meta‐analysis
Authors: Qi Wei‐Xiang , He Ai‐Na , Shen Zan , Yao Yang 
Published: April 2013

AimsTo investigate the overall incidence and risk of hypertension in cancer patients who receive axitinib and compare the differences in incidences between axitinib and the other four approved vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs).MethodsSeveral databases were searched, including Pubmed, Embase and Cochrane databases. Eligible studies were phase II and III prospective clinical trials of patients with cancer assigned axitinib at a starting dose of 5 mg orally twice daily with data on hypertension available. Overall incidence rates, relative risk (RR), and 95% confidence intervals (CI) were calculated employing fixed or random effects models depending on the heterogeneity of the included trials.ResultsA total of 1908 patients from 10 clinical trials were included. The overall incidences of all grade and high grade hypertension in cancer patients were 40.1% (95% CI 30.9, 50.2%) and 13.1% (95% CI 6.7, 24%). The use of axitinib was associated with significantly increased risk of all grade (RR 3.00, 95% CI 1.29, 6.97, P = 0.011) and high grade hypertension (RR1.71, 95% CI 1.21, 2.43, P = 0.003). The risk of axitinib associated all grade and high grade hypertension in renal cell carcinoma (RCC) was significantly higher than that in non‐RCC. Additionally, the risk of hypertension with axitinib was substantially higher than other approved VEGFR‐TKIs, while the risk of all grade hypertension with axitinib was similar to pazopanib (RR 1.05; 95% CI 0.95‐, 1.17, P = 0.34).ConclusionsWhile sharing a similar spectrum of target receptors with other VEGFR‐TKIs, axitinib is associated with an unexpectedly high risk of developing hypertension. Close monitoring and appropriate management for hypertension are recommended during the treatment.
Not‐in‐trial simulation I: Bridging cardiovascular risk from clinical trials to real‐life conditions
Authors: Chain Anne S. Y. , Dieleman Jeanne P. , van Noord Charlotte , Hofman Albert , Stricker Bruno H. Ch. , Danhof Meindert , Sturkenboom Miriam C. J. M. , Della Pasqua Oscar 
Published: April 2013

AimsThe assessment of heart rate‐corrected QT (QTc) interval prolongation relies on the evidence of drug effects in healthy subjects. This study demonstrates the relevance of pharmacokinetic–pharmacodynamic (PKPD) relationships to characterize drug‐induced QTc interval prolongation and explore the discrepancies between clinical trials and real‐life conditions.Methodsd,l‐Sotalol data from healthy subjects and from the Rotterdam Study cohort were used to assess treatment response in a phase I setting and in a real‐life conditions, respectively. Using modelling and simulation, drug effects at therapeutic doses were predicted in both populations.ResultsInclusion criteria were shown to restrict the representativeness of the trial population in comparison to real‐life conditions. A significant part of the typical patient population was excluded from trials due to weight and baseline QTc interval criteria. Relative risk was significantly different between sotalol users with and without heart failure, hypertension, diabetes and myocardial infarction (P < 0.01). Although drug effects do cause an increase in the relative risk of QTc interval prolongation, the presence of diabetes represented an increase from 4.0 [95% confidence interval (CI) 2.7–5.8] to 6.5 (95% CI 1.6–27.1), whilst for myocardial infarction it increased from 3.4 (95% CI 2.3–5.13) to 15.5 (95% CI 4.9–49.3).ConclusionsOur findings show that drug effects on QTc interval do not explain the observed QTc values in the population. The prevalence of high QTc values in the real‐life population can be assigned to co‐morbidities and concomitant medications. These findings substantiate the need to account for these factors when evaluating the cardiovascular risk of medicinal products.
Chronic lymphocytic leukaemia – the role of the microenvironment pathogenesis and therapy
Authors: Ramsay Alan D. , Rodriguez‐Justo Manuel 
Published: April 2013

SummaryChronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL) is one of the more common forms of B cell malignancy. Although the condition has a variable clinical course, the trend is towards eventual relapse and the disease is considered incurable. Whilst the majority of the circulating CD5‐positive neoplastic B cells are arrested in the G0 phase of the cell cycle, those in the bone marrow and lymphoid tissues proliferate at a rate of 0·1–1% of the entire clone per day. This proliferation is supported by the tissue microenvironment, which has been shown to induce upregulation of anti‐apoptotic proteins and enhance the survival of the neoplastic cells. Microenvironmental factors are also thought to be important in tumour relapse and resistance to therapy. This review outlines the main signalling pathways involved in these tumour cell‐stromal interactions, and includes potential therapeutic strategies based on the manipulation of key components within the CLL microenvironment.
Use of a biosimilar granulocyte colony‐stimulating factor for peripheral blood stem cell mobilization: an analysis of mobilization and engraftment
Authors: Publicover Amy , Richardson Deborah S. , Davies Andrew , Hill Kate S. , Hurlock Carol , Hutchins David , Jenner Matthew W. , Johnson Peter W. , Lamb Jane , Launders Harriet , McKeag Nikki , Newman Joan , Orchard Kim H. 
Published: April 2013

SummaryPeripheral blood haematopoietic progenitor cell mobilization has become a standard procedure prior to autologous stem cell transplantation. Biosimilar granulocyte colony‐stimulating factors (GCSF) have recently been awarded European Union (EU) licences for stem cell mobilization but data for their use in this context remain limited. The biosimilar GCSF, Ratiograstim® (Ratiopharm, Ulm, Germany) was granted an EU licence in September 2008 and incorporated into clinical practice in the Wessex Blood and Marrow Transplantation Programme in December 2008. Data were retrospectively collected for 154 consecutive patients undergoing peripheral blood stem cell harvest between January 2009 and December 2011 using the biosimilar GCSF. 131 consecutive patients from the preceding 3 years, who had received Neupogen®, were used as a control. We analysed both parameters relevant to stem cell collection and engraftment data, where patients proceeded to transplantation. We found no statistically significant difference between the two groups when comparing CD34 predictors, total number of CD34+ stem cells collected, number of days required for collection, or for time to engraftment. This is, to our knowledge, the largest direct comparison of a biosimilar GCSF with originator GCSF for stem cell mobilization. The use of biosimilar GCSF can produce a significant cost saving, allowing investment in other areas of stem cell transplantation.
CD43 expression is associated with inferior survival in the non‐germinal centre B‐cell subgroup of diffuse large B‐cell lymphoma
Authors: Mitrovic Zdravko , Iqbal Javeed , Fu Kai , Smith Lynette M. , Bast Martin , Greiner Timothy C. , Aoun Patricia , Armitage James O. , Vose Julie M. , Weisenburger Dennis D. , Chan Wing C. 
Published: April 2013

SummaryWe evaluated the prognostic significance of CD43 (SPN), a membrane glycoprotein, in 140 patients with diffuse large B‐cell lymphoma (DLBCL) by tissue microarray (TMA) immunostaining, and gene expression profiling (GEP) in 43 patients. CD43 protein was expressed in 19% of the cases and was strongly related to the non‐germinal centre B‐cell (non‐GCB) subgroup by both TMA and GEP. Patients with CD43(+) DLBCL had an inferior 3‐year overall survival (OS) compared to those with CD43(‐) DLBCL (50% vs. 76%, P = 0·01). Within the non‐GCB subgroup, patients with CD43(+) DLBCL had a particularly poor 3‐year OS (32% vs. 71%, P < 0·001). Gene set enrichment analysis within the activated B‐cell subgroup revealed significant enrichment in the stromal‐1 signature in CD43(−) cases. We conclude that CD43 is an adverse prognostic marker in DLBCL, and is preferentially expressed in the non‐GCB subgroup. The dismal outcome of CD43(+) cases in the non‐GCB subgroup may be explained, at least in part, by a less favourable microenvironment.
Angiogenin outperforms VEGF, EPCs and CECs in predicting Dukes' and AJCC stage in colorectal cancer
Authors: Ramcharan Sean K. , Lip Gregory Y. H. , Stonelake Paul S. , Blann Andrew D. 
Published: April 2013

AbstractBackgroundCirculating endothelial cells (CECs), endothelial progenitor cells (EPCs), Willebrand factor (vWf), soluble E‐selectin, vascular endothelial growth factor (VEGF) and angiogenin are of interest in cancer vascular biology. However, few studies have looked at more than one in combination. We set out to determine which would be best in predicting the Dukes' and American Joint Committee on Cancer (AJCC) scores in colorectal cancer patients.MethodsWe recruited 154 patients with colorectal cancer, 29 healthy controls and 26 patients with benign bowel disease. CD34+/CD45−/CD146+ CECs and CD34+/CD45−/CD309[KDR]+ EPCs were measured by flow cytometry, plasma markers by ELISA.ResultsAll research indices were raised in colorectal cancer (P < 0·05) compared to control groups. Although CECs (P < 0·05), EPCs (P < 0·01) and angiogenin (P < 0·01) increased stepwise across the four Dukes' stages and four AJCC stages, only angiogenin remained significant in multiple regression analysis (P = 0·003 for Dukes, P = 0·01 for AJCC). Angiogenin levels were higher in Dukes' stages C and D compared to stage A, and AJCC stages 4–6 and 7–10 compared to stage 1 (all P < 0·05). Adding a second research marker to angiogenin did not markedly improve this relationship.ConclusionAlthough we found disturbances in endotheliod cells and plasma markers of the endothelium and growth factors, only angiogenin levels were independently associated with progression of the Dukes' stage and AJCC stage, with the association with Duke's stage being stronger. We suggest that angiogenin is a potential biomarker in risk stratification for colorectal cancer, and may aid clinical decision making.
Seeking a Sex‐Specific Coolidge Effect in a Simultaneous Hermaphrodite
Authors: Werminghausen Johanna , Lange Rolanda , Anthes Nils 
Published: April 2013

AbstractIn polygamous mating systems, a capability to discriminate against familiar mates may be beneficial to both sexes. Polyandrous females, for instance, may enhance the odds of finding sires with optimal genetic compatibility or high genetic quality by mating with multiple different males; polygynous males, in addition, may more efficiently invest their limited ejaculates across multiple (rather than single) females. The Coolidge effect facilitates this kind of mate discrimination, as sexual motivation declines across consecutive copulations with a familiar partner but resurrects with a novel mate. In simultaneous hermaphrodites, we expect the Coolidge effect to show sex role‐dependent patterns and vary with previous sex‐specific mating activity. Using the promiscuous hermaphroditic sea slug Chelidonura sandrana, we investigated (1) whether sexual motivation indeed declines when repeatedly exposed to familiar partners, (2) whether the Coolidge effect occurs in a sex‐specific manner and (3) whether ejaculation is strategic with respect to partner familiarity. We found neither mating latency, nor penis intromission duration, mating propensity or the frequency of sex role alternations to vary significantly with treatments. Furthermore, slugs did not donate larger ejaculates to novel than to familiar partners. Partner novelty thus elicited no detectable response in sexual motivation or mating effort in C. sandrana. We suggest that the sea slugs' promiscuous mating system in often large mating aggregations makes mate discrimination based on novelty obsolete in comparison with more relevant criteria such as partner body size or mating history.
From Policy to Implementation—How Family Relationship Centres Became a Reality
Authors: Pidgeon Sue 
Published: April 2013

This article deals with the process undertaken by the Australian Government to develop and implement Family Relationship Centres (FRCs) as part of a major package of reforms to the Australian family law system. The article outlines consultation undertaken in developing the reforms and explains the role of the FRCs. The article details the practical steps taken to roll‐out the new FRCs. The services were to be outsourced to community‐based service providers but there were many issues for the Government to address, including: how an FRC should operate; where they should be located; how to allocate the funding; and how to manage the roll‐out of so many services. Other aspects of the implementation covered in the article include: addressing accessibility and quality control issues; training FRC staff; establishing a national telephone advice line and website; and informing the public about the new services. The article also refers to steps taken to support the introduction of compulsory dispute resolution; and research and evaluation undertaken to measure the impact of the reforms.
Keypoints for the Family Court Community
Family Relationship Centres (FRCs) were a new type of service and their development and implementation raised a range of issues to be dealt with by the Australian Government.
Determining where and when FRCs would be rolled out, selecting community‐based service providers, addressing accessibility and quality control issues, training FRC staff and raising public awareness of the new services were all part of the implementation process.
As brand new services, FRCs were able to be innovative and to develop new processes (and adapt old ones) to suit their role as an alternative to the courts and as a doorway to the wider family law system.
Child Protection in Family Relationship Centres: Innovations in Western Australia
Authors: Hannan Jennifer 
Published: April 2013

Family Relationship Centres (FRCs) established in Australia in 2006 are seeing parents from increasingly complex backgrounds including families where child protection matters may be of serious concern. These matters have required practitioners to shift their thinking about what responsibility they have for hearing the voices of children and their role in child protection. Many of the safety issues that present at FRC's fall below the statutory threshold for child protection intervention and this paper argues that FRC's are well placed to act as a referral and assessment point for families who might not otherwise be assessed or referred to services. This paper outlines a model of child inclusive practice (CIP) used in Anglicare WA's FRC's which is child inclusive but does not proceed to family dispute resolution. Where a risk factor such as family violence, mental health issues, or drug and alcohol issues is identified on intake with parents, children are routinely seen for an interview in order to obtain information about their needs and wellbeing. Literature indicates that many victims minimise violence and the risks associated with it; many parents maintain child contact with perpetrators for fear of retaliation; and many children protect their parents by not disclosing violence or other issues, because they do not want to “add fuel to the fire” or “be disloyal” to a parent. Case studies are provided to underline the importance of safety assessment.
Keypoints for the Family Court Community
High numbers of complex child protection matters that present at Family Law services
Importance of undertaking a safety assessment with children as well as parents where indicated
Importance of referral to support services even if cases do not reach child protection threshold
Thioredoxin h regulates calcium dependent protein kinases in plasma membranes
Authors: Ueoka‐Nakanishi Hanayo , Sazuka Takashi , Nakanishi Yoichi , Maeshima Masayoshi , Mori Hitoshi , Hisabori Toru 
Published: April 2013

Thioredoxin (Trx) is a key player in redox homeostasis in various cells, modulating the functions of target proteins by catalyzing a thiol–disulfide exchange reaction. Target proteins of cytosolic Trx‐h of higher plants were studied, particularly in the plasma membrane, because plant plasma membranes include various functionally important protein molecules such as transporters and signal receptors. Plasma membrane proteins from Arabidopsis thaliana cell cultures were screened using a resin Trx‐h1 mutant‐immobilized, and a total of 48 candidate proteins obtained. These included two calcium‐sensing proteins: a phosphoinositide‐specific phospholipase 2 (AtPLC2) and a calcium‐dependent protein kinase 21 (AtCPK21). A redox‐dependent change in AtCPK21 kinase activity was demonstrated in vitro. Oxidation of AtCPK21 resulted in a decrease in kinase activity to 19% of that of untreated AtCPK21, but Trx‐h1 effectively restored the activity to 90%. An intramolecular disulfide bond (Cys97–Cys108) that is responsible for this redox modulation was then identified. In addition, endogenous AtCPK21 was shown to be oxidized in vivo when the culture cells were treated with H2O2. These results suggest that redox regulation of AtCPK21 by Trx‐h in response to external stimuli is important for appropriate cellular responses. The relationship between the redox regulation system and Ca2+ signaling pathways is discussed.Structured digital abstract

CPK21 physically interacts with TRXH1 by two hybrid (View interaction)

TRXH1 physically interacts with AT1G56075, CPK21, PRX2B, HIR3, RAA4B, TC132, RAD2C, AT3G03270, AT3G53990, METK4, AT3G17020, AT1G20760, MPCP3, SKS2, AT5G23890, DTC, AT1G56070, TBB3, ACT8, TI110, DHSB1, TBA3, AOX1A, PLCD2, CLAH1, CLAH2, RSSA1, APX1, RAB1C, ACT7, ARF1, NRL1, ADT1, TBB7, RAD2A, G3PC1, TBB4, MD37E, DHSA1, TC159, AT4G22710, GPX6, RABC1, VATA, GPX2 and RAA2A by affinity chromatography technology (View interaction)
Kienböck's disease associated with radiocephalic fistula formation in a patient with end‐stage renal disease
Authors: Kang Gun Woo , Lee Da Young , Lee Young‐Hwan , Ahn Ki Sung , Kim Shin‐Kun , Lee In Hee 
Published: April 2013

AbstractKienböck's disease, which consists of osteonecrosis and collapse of the lunate bone, causes chronic pain and dysfunction of the wrist. Patients on hemodialysis are occasionally present with wrist pain, but Kienböck's disease is rarely reported in dialysis patients. This case study describes Kienböck's disease in a patient with end‐stage renal disease on hemodialysis. A 39‐year‐old male with a 1‐year history of hemodialysis presented with left wrist pain that increased progressively over 6 months. The patient had no history of trauma or any other risk factors known to be associated with Kienböck's disease. Physical examination of the wrist at the site of the arteriovenous fistula showed swelling and tenderness with decreased range of motion. Radiographic examination showed articular collapse and fracture of the body of lunate consistent with stage IIIb Kienböck's disease. An intercarpal arthrodesis with autogenous bone graft was performed.
Formation and removal of apical vapor lock during syringe irrigation: a combined experimental and Computational Fluid Dynamics approach
Authors: Boutsioukis C. , Kastrinakis E. , Lambrianidis T. , Verhaagen B. , Versluis M. , van der Sluis L. W. M. 
Published: April 2013

AbstractAim(i) To evaluate the effect of needle type and insertion depth, root canal size and irrigant flow rate on the entrapment of air bubbles in the apical part of a root canal (apical vapor lock) during syringe irrigation using experiments and a Computational Fluid Dynamics (CFD) model, (ii) to investigate whether the irrigant contact angle affects bubble entrapment, (iii) to examine if an established vapor lock can be removed by syringe irrigation.MethodologyBubble entrapment during irrigation of straight artificial root canals of size 35 or 50 was evaluated by real‐time visualizations. The irrigant was delivered by a closed‐ended or an open‐ended needle positioned at 1 or 3 mm short of working length (WL) and at a flow rate of 0.033–0.260 mL s−1. Results were analysed by nonparametric tests at 0.05 significance. Selected cases were also simulated by a two‐phase CFD model.ResultsA vapor lock was observed in 48% of the cases investigated experimentally. Increasing the apical size, using an open‐ended needle, positioning the needle closer to WL and delivering the irrigant at higher flow rate resulted in significantly smaller vapor lock. An increased contact angle resulted in the entrapment of a larger bubble when a low flow rate was used. Both brief insertion of the needle to WL whilst irrigating at a flow rate of 0.083 mL s−1and delivering the irrigant at 0.260 mL s−1without changing the needle position were capable of removing an established vapor lock.ConclusionsApical vapor lock may occur under certain conditions, but appears to be easily prevented or removed by syringe irrigation.