bluuebunny/crossref_metadata_2025_split huggingface dataset:
Service configuration, unit characteristics and variation in intervention rates in a national sample of obstetric units in England: an exploratory analysis
Authors: Rowe Rachel E , Townend John , Brocklehurst Peter , Knight Marian , Macfarlane Alison , McCourt Christine , Newburn Mary , Redshaw Maggie , Sandall Jane , Silverton Louise , Hollowell Jennifer 
Published: May 2014

ObjectivesTo explore whether service configuration and obstetric unit (OU) characteristics explain variation in OU intervention rates in ‘low-risk’ women.DesignEcological study using funnel plots to explore unit-level variations in adjusted intervention rates and simple linear regression, stratified by parity, to investigate possible associations between unit characteristics/configuration and adjusted intervention rates in planned OU births. Characteristics considered: OU size, presence of an alongside midwifery unit (AMU), proportion of births in the National Health Service (NHS) trust planned in midwifery units or at home and midwifery ‘under’ staffing.Setting36 OUs in England.Participants‘Low-risk’ women with a ‘term’ pregnancy planning vaginal birth in a stratified, random sample of 36 OUs.Main outcome measuresAdjusted rates of intrapartum caesarean section, instrumental delivery and two composite measures capturing birth without intervention (‘straightforward’ and ‘normal’ birth).ResultsFunnel plots showed unexplained variation in adjusted intervention rates. In NHS trusts where proportionately more non-OU births were planned, adjusted intrapartum caesarean section rates in the planned OU births were significantly higher (nulliparous: R2=31.8%, coefficient=0.31, p=0.02; multiparous: R2=43.2%, coefficient=0.23, p=0.01), and for multiparous women, rates of ‘straightforward’ (R2=26.3%, coefficient=−0.22, p=0.01) and ‘normal’ birth (R2=17.5%, coefficient=0.24, p=0.01) were lower. The size of the OU (number of births), midwifery ‘under’ staffing levels (the proportion of shifts where there were more women than midwives) and the presence of an AMU were associated with significant variation in some interventions.ConclusionsTrusts with greater provision of non-OU intrapartum care may have higher intervention rates in planned ‘low-risk’ OU births, but at a trust level this is likely to be more than offset by lower intervention rates in planned non-OU births. Further research using high quality data on unit characteristics and outcomes in a larger sample of OUs and trusts is required.
Patient complaints in healthcare systems: a systematic review and coding taxonomy
Authors: Reader Tom W , Gillespie Alex , Roberts Jane 
Published: May 2014

BackgroundPatient complaints have been identified as a valuable resource for monitoring and improving patient safety. This article critically reviews the literature on patient complaints, and synthesises the research findings to develop a coding taxonomy for analysing patient complaints.MethodsThe PubMed, Science Direct and Medline databases were systematically investigated to identify patient complaint research studies. Publications were included if they reported primary quantitative data on the content of patient-initiated complaints. Data were extracted and synthesised on (1) basic study characteristics; (2) methodological details; and (3) the issues patients complained about.Results59 studies, reporting 88 069 patient complaints, were included. Patient complaint coding methodologies varied considerably (eg, in attributing single or multiple causes to complaints). In total, 113 551 issues were found to underlie the patient complaints. These were analysed using 205 different analytical codes which when combined represented 29 subcategories of complaint issue. The most common issues complained about were ‘treatment’ (15.6%) and ‘communication’ (13.7%). To develop a patient complaint coding taxonomy, the subcategories were thematically grouped into seven categories, and then three conceptually distinct domains. The first domain related to complaints on the safety and quality of clinical care (representing 33.7% of complaint issues), the second to the management of healthcare organisations (35.1%) and the third to problems in healthcare staff–patient relationships (29.1%).ConclusionsRigorous analyses of patient complaints will help to identify problems in patient safety. To achieve this, it is necessary to standardise how patient complaints are analysed and interpreted. Through synthesising data from 59 patient complaint studies, we propose a coding taxonomy for supporting future research and practice in the analysis of patient complaint data.
Equilibrium geometries, electronic and magnetic properties of small AunNi- (n = 1-9) clusters
Authors: Tang Cui-Ming , Chen Xiao-Xu , Yang Xiang-Dong 
Published: May 2014

Geometrical, electronic and magnetic properties of small Au n Ni - (n = 1-9) clusters have been investigated based on density functional theory (DFT) at PW91P86 level. An extensive structural search shows that the relative stable structures of Au n Ni - (n = 1-9) clusters adopt 2D structure for n = 1-5, 7 and 3D structure for n = 6, 8-9. And the substitution of a Ni atom for an Au atom in the [Formula: see text] cluster obviously changes the structure of the host cluster. Moreover, an odd–even alternation phenomenon has been found for HOMO–LUMO energy gaps, indicating that the relative stable structures of the Au n Ni - clusters with odd-numbered gold atoms have a higher relative stability. Finally, the natural population analysis (NPA) and the vertical detachment energies (VDE) are studied, respectively. The theoretical values of VDE are reported for the first time to our best knowledge.
POSTEROLATERAL ROTATORY INSTABILITY OF THE ELBOW AFTER CORRECTIVE OSTEOTOMY FOR PREVIOUSLY ASYMPTOMATIC CUBITUS VARUS DEFORMITY
Authors: Seo Sang Gyo , Gong Hyun Sik , Lee Young Ho , Rhee Seung Hwan , Lee Hyuk Jin , Baek Goo Hyun 
Published: May 2014

Background: We identified a subset of patients who had posterolateral rotatory instability (PLRI) following corrective osteotomy for asymptomatic cubitus varus deformity. We aimed to identify risk factors for PLRI in such patients by comparing this subgroup to patients who did not demonstrate PLRI following osteotomy.Methods: We retrospectively reviewed the medical records and radiographs of 22 patients with cubitus varus that underwent corrective osteotomy at our institution between 2003 and 2010. All patients underwent surgery for cosmetic reasons, and no patient reported functional problems such as PLRI or ulnar nerve symptoms pre-operatively. We sought to identify differences between those that experienced an increase in PLRI after osteotomy (PLRI group) and those that did not (non-PLRI group) with regard to demographics, degree of deformity, amount of surgical correction, and final outcomes.Results: Five patients had PLRI after osteotomy, and all five subsequently underwent lateral ulnar collateral ligament reconstruction using a triceps tendon graft. No statistically significant difference was observed between the PLRI and non-PLRI groups in terms of demographics, degree of deformity, amount of surgical correction, range of motion, and final Mayo Elbow Performance Index (MEPI) and the Disabilities of Arm, Shoulder, and Hand (DASH) scores. However, the PLRI group had marginally greater medial displacement of the distal fragment.Conclusions: This study demonstrates that PLRI can become apparent after corrective osteotomy for cubitus varus in the absence of clinical symptoms of instability preoperatively. We suggest that careful examination for PLRI should be performed after surgical correction for cubitus varus deformity, and surgeons should be prepared to proceed with simultaneous reconstruction of the lateral ligaments of the elbow.
ANATOMY OF THE EXTENSOR POLLICIS BREVIS ASSOCIATED WITH AN EXTENSION MECHANISM OF THE THUMB METACARPOPHALANGEAL JOINT
Authors: Shigematsu Shinsuke , Shimizu Hiroyuki , Beppu Moroe , Hirata Kazuaki 
Published: May 2014

This study aimed to determine whether the extensor pollicis longus (EPL) or abductor pollicis longus (APL) can replace the function of thumb extension in hands in which the extensor pollicis brevis (EPB) is absent. Cadaver dissection was performed to examine anatomical association between the interphalangeal (IP) joint and metacarpophalangeal (MP) joint of the thumb, as well as extension mechanism in clinical cases. EPB insertion could be classified into eight types, and the EPB was absent in 7.6% of all cases. In hands without an EPB, the width of the EPL tendon tended to be wider, and the number of APL tendons was significantly greater than in hands with an EPB. In hands without an EPB, the EPL and APL may replace the function of the EPB. As a result, a greater load is imposed on these two tendons than in hands with the EPB.
TREATMENT OF EXTRA-ARTICULAR DISTAL RADIAL MALUNION WITH PERCUTANEOUS OSTEOTOMY AND AN INTRAMEDULLARY IMPLANT
Authors: Takahashi Mitsuhiko , Tonogai Ichiro , Sairyo Koichi 
Published: May 2014

Purpose: Distal radius malunion is often seen after distal radius fracture. We performed a less invasive but secure corrective surgery using an intramedullary implant combined with percutaneous osteotomy. The purpose of this study was to evaluate the results of this surgical technique.Patients and methods: Three patients with malunion of a distal radius fracture were included. We assessed the wrist joint disability scores pre-operatively and at the final follow-up an average of 21 months after surgery. We also performed radiological assessments of volar tilt, radial inclination, and ulnar variance.Results: All three patients achieved excellent clinical results with an average joint disability score of 93.3 at the final follow-up. The radiological parameters improved without any post-operative correction loss.Discussion: Intramedullary implant combined with percutaneous osteotomy provides sufficient stability after correction of distal radius malunion and avoids the complications associated with the use of a volar plate.
Neuromedin U: A Candidate Biomarker and Therapeutic Target to Predict and Overcome Resistance to HER-Tyrosine Kinase Inhibitors
Authors: Rani Sweta , Corcoran Claire , Shiels Liam , Germano Serena , Breslin Susan , Madden Stephen , McDermott Martina S. , Browne Brigid C. , O'Donovan Norma , Crown John , Gogarty Martina , Byrne Annette T. , O'Driscoll Lorraine 
Published: May 2014

Abstract
Intrinsic and acquired resistance to HER-targeting drugs occurs in a significant proportion of HER2-overexpressing breast cancers. Thus, there remains a need to identify predictive biomarkers that could improve patient selection and circumvent these types of drug resistance. Here, we report the identification of neuromedin U (NmU) as an extracellular biomarker in cells resistant to HER-targeted drugs. NmU overexpression occurred in cells with acquired or innate resistance to lapatinib, trastuzumab, neratinib, and afatinib, all of which displayed a similar trend upon short-term exposure, suggesting NmU induction may be an early response. An analysis of 3,489 cases of breast cancer showed NmU to be associated with poor patient outcome, particularly those with HER2-overexpressing tumors independent of established prognostic indicators. Ectopic overexpression of NmU in drug-sensitive cells conferred resistance to all HER-targeting drugs, whereas RNAi-mediated attenuation sensitized cells exhibiting acquired or innate drug resistance. Mechanistic investigations suggested that NmU acted through HSP27 as partner protein to stabilize HER2 protein levels. We also obtained evidence of functional NmU receptors on HER2-overexpressing cells, with the addition of exogenous NmU eliciting an elevation in HER2 and EGFR expression along with drug resistance. Finally, we found that NmU seemed to function in cell motility, invasion, and anoikis resistance. In vivo studies revealed that NmU attenuation impaired tumor growth and metastasis. Taken together, our results defined NmU as a candidate drug response biomarker for HER2-overexpressing cancers and as a candidate therapeutic target to limit metastatic progression and improve the efficacy of HER-targeted drugs. Cancer Res; 74(14); 3821–33. ©2014 AACR.
Molecular Imaging with Bioluminescence and PET Reveals Viral Oncolysis Kinetics and Tumor Viability
Authors: Kuruppu Darshini , Brownell Anna-Liisa , Shah Khalid , Mahmood Umar , Tanabe Kenneth K. 
Published: May 2014

Abstract
Viral oncolysis, the destruction of cancer cells by replicating virus, is an experimental cancer therapy that continues to be explored. The treatment paradigm for this therapy involves successive waves of lytic replication in cancer cells. At present, monitoring viral titer at sites of replication requires biopsy. However, repeat serial biopsies are not practically feasible for temporal monitoring of viral replication and tumor response in patients. Molecular imaging provides a noninvasive method to identify intracellular viral gene expression in real time. We imaged viral oncolysis and tumor response to oncolysis sequentially with bioluminescence and positron emission tomography (PET), revealing the kinetics of both processes in tumor xenografts. We demonstrate that virus replication cycles can be identified as successive waves of reporter expression that occur ∼2 days after the initial viral tumor infection peak. These waves correspond to virions that are released following a replication cycle. The viral and cellular kinetics were imaged with Fluc and Rluc bioluminescence reporters plus two 18F-labeled PET reporters FHBG [9-(4-18F-fluoro-3-[hydroxymethyl] butyl) guanine] and FLT (18F-3′-deoxy-3-′fluorothymidine), respectively. Correlative immunohistochemistry on tumor xenograft sections confirmed in vivo results. Our findings show how PET can be used to identify virus replication cycles and for real-time measurements of intratumoral replicating virus levels. This noninvasive imaging approach has potential utility for monitoring viral oncolysis therapy in patients. Cancer Res; 74(15); 4111–21. ©2014 AACR.
CSPG4-Specific Immunity and Survival Prolongation in Dogs with Oral Malignant Melanoma Immunized with Human CSPG4 DNA
Authors: Riccardo Federica , Iussich Selina , Maniscalco Lorella , Lorda Mayayo Saray , La Rosa Giuseppe , Arigoni Maddalena , De Maria Raffaella , Gattino Francesca , Lanzardo Stefania , Lardone Elena , Martano Marina , Morello Emanuela , Prestigio Simone , Fiore Alessandra , Quaglino Elena , Zabarino Sara , Ferrone Soldano , Buracco Paolo , Cavallo Federica 
Published: May 2014

AbstractPurpose: Due to the many similarities with its human counterpart, canine malignant melanoma (cMM) is a valuable model in which to assess the efficacy of novel therapeutic strategies. The model is herein used to evaluate the immunogenicity, safety, and therapeutic efficacy of a human chondroitin sulfate proteoglycan-4 (hCSPG4) DNA-based vaccine. The fact that homology between hCSPG4 and cCSPG4 amino-acidic sequences stands at more than 80% provides the rationale for using an hCSPG4 DNA vaccine in the cMM model.Experimental Design: Dogs with stage II–III surgically resected CSPG4-positive oral MM were subjected to monthly intramuscular plasmid administration, which was followed immediately by electroporation (electrovaccination) for at least 6, and up to 20, months. The immunogenicity, safety, and therapeutic efficacy of the vaccine have been evaluated.Results: hCSPG4 electrovaccination caused no clinically relevant local or systemic side effects and resulted in significantly longer overall and disease-free survival times in 14 vaccinated dogs as compared with 13 nonvaccinated controls. All vaccinated dogs developed antibodies against both hCSPG4 and cCSPG4. Seven vaccinated dogs were also tested for a cCSPG4-specific T-cell response and only two gave a detectable interferon (IFN)γ response.Conclusion: Xenogeneic electrovaccination against CSPG4 is able to overcome host unresponsiveness to the “self” antigen and seems to be effective in treating cMM, laying the foundation for its translation to a human clinical setting. Clin Cancer Res; 20(14); 3753–62. ©2014 AACR.
Molecular Pathways: The Immunogenic Effects of Platinum-Based Chemotherapeutics
Authors: Hato Stanleyson V. , Khong Andrea , de Vries I. Jolanda M. , Lesterhuis W. Joost 
Published: May 2014

Abstract
The platinum-based drugs cisplatin, carboplatin, and oxaliplatin belong to the most widely used chemotherapeutics in oncology, showing clinical efficacy against many solid tumors. Their main mechanism of action is believed to be the induction of cancer cell apoptosis as a response to their covalent binding to DNA. In recent years, this picture has increased in complexity, based on studies indicating that cellular molecules other than DNA may potentially act as targets, and that part of the antitumor effects of platinum drugs occurs through modulation of the immune system. These immunogenic effects include modulation of STAT signaling; induction of an immunogenic type of cancer cell death through exposure of calreticulin and release of ATP and high-mobility group protein box-1 (HMGB-1); and enhancement of the effector immune response through modulation of programmed death receptor 1-ligand and mannose-6-phosphate receptor expression. Both basic and clinical studies indicate that at least part of the antitumor efficacy of platinum chemotherapeutics may be due to immune potentiating mechanisms. Clinical studies exploiting this novel mechanism of action of these old cancer drugs have been initiated. Here, we review the literature on the immunogenic effects of platinum, summarize the clinical advances using platinum as a cytotoxic compound with immune adjuvant properties, and discuss the limitations to these studies and the gaps in our understanding of the immunologic effects of these drugs. Clin Cancer Res; 20(11); 2831–7. ©2014 AACR.
Inflammatory Myofibroblastic Tumors Harbor Multiple Potentially Actionable Kinase Fusions
Authors: Lovly Christine M. , Gupta Abha , Lipson Doron , Otto Geoff , Brennan Tina , Chung Catherine T. , Borinstein Scott C. , Ross Jeffrey S. , Stephens Philip J. , Miller Vincent A. , Coffin Cheryl M. 
Published: May 2014

Abstract
Inflammatory myofibroblastic tumor (IMT) is a neoplasm that typically occurs in children. The genetic landscape of this tumor is incompletely understood and therapeutic options are limited. Although 50% of IMTs harbor anaplastic lymphoma kinase (ALK) rearrangements, no therapeutic targets have been identified in ALK-negative tumors. We report for the first time that IMTs harbor other actionable targets, including ROS1 and PDGFRβ fusions. We detail the case of an 8-year-old boy with treatment-refractory ALK-negative IMT. Molecular tumor profiling revealed a ROS1 fusion, and he had a dramatic response to the ROS1 inhibitor crizotinib. This case prompted assessment of a larger series of IMTs. Next-generation sequencing revealed that 85% of cases evaluated harbored kinase fusions involving ALK, ROS1, or PDGFRβ. Our study represents the most comprehensive genetic analysis of IMTs to date and also provides a rationale for routine molecular profiling of these tumors to detect therapeutically actionable kinase fusions.
Significance: Our study describes the most comprehensive genomics-based evaluation of IMT to date. Because there is no “standard-of-care” therapy for IMT, the identification of actionable genomic alterations, in addition to ALK, is expected to redefine management strategies for patients with this disease. Cancer Discov; 4(8); 889–95. ©2014 AACR.
See related commentary by Le and Doebele, p. 870
This article is highlighted in the In This Issue feature, p. 855
Mediation of Cardiovascular Risk Factor Effects Through Subclinical Vascular Disease
Authors: Yeboah Joseph , Delaney Joseph A. , Nance Robin , McClelland Robyn L. , Polak Joseph F. , Sibley Christopher T. , Bertoni Alain , Burke Gregory L. , Carr J. Jeffery , Herrington David M. 
Published: May 2014

Objective—
It is unclear to what extent subclinical cardiovascular disease (CVD) such as coronary artery calcium (CAC), carotid intima-media thickness (CIMT), and brachial flow-mediated dilation (FMD) are mediators of the known associations between traditional cardiovascular risk factors and incident CVD events. We assessed the portion of the effects of risk factors on incident CVD events that are mediated through CAC, CIMT, and FMD.

Approach and Results—
Six thousand three hundred fifty-five of 6814 Multi-Ethnic Study of Atherosclerosis participants were included. Nonlinear implementation of structural equation modeling (STATA mediation package) was used to assess whether CAC, CIMT, or FMD are mediators of the association between traditional risk factors and incident CVD event. Mean age was 62 years, with 47% men, 12% diabetics, and 13% current smokers. After a mean follow-up of 7.5 years, there were 539 CVD adjudicated events. CAC showed the highest mediation while FMD showed the least. Age had the highest percent of total effect mediated via CAC for CVD outcomes, whereas current cigarette smoking had the least percent of total effect mediated via CAC (percent [95% confidence interval]: 80.2 [58.8–126.7] versus 10.6 [6.1–38.5], respectively). Body mass index showed the highest percent of total effect mediated via CIMT (17.7 [11.6–38.9]); only a negligible amount of the association between traditional risk factors and CVD was mediated via FMD.

Conclusions—
Many of the risk factors for incident CVD (other than age, sex, and body mass index) showed a modest level of mediation via CAC, CIMT, and FMD, suggesting that current subclinical CVD markers may not be optimal intermediaries for gauging upstream risk factor modification.
Influence of Previous Heart Failure Hospitalization on Cardiovascular Events in Patients With Reduced and Preserved Ejection Fraction
Authors: Bello Natalie A. , Claggett Brian , Desai Akshay S. , McMurray John J.V. , Granger Christopher B. , Yusuf Salim , Swedberg Karl , Pfeffer Marc A. , Solomon Scott D. 
Published: May 2014

Background—
Hospitalization for acute heart failure (HF) is associated with high rates of subsequent mortality and readmission. We assessed the influence of the time interval between previous HF hospitalization and randomization in the Candesartan in Heart failure: Reduction in Mortality and morbidity (CHARM) trials on clinical outcomes in patients with both reduced and preserved ejection fraction.

Methods and Results—
CHARM enrolled 7599 patients with New York Heart Association class II to IV HF, of whom 5426 had a history of previous HF hospitalization. Cox proportional hazards regression models were used to assess the association between time from previous HF hospitalization and randomization and the primary outcome of cardiovascular death or unplanned admission to hospital for the management of worsening HF during a median of 36.6 months. For patients with HF and reduced or preserved ejection fraction, rates of cardiovascular mortality and HF hospitalization were higher among patients with previous HF hospitalization than those without. The risk for mortality and hospitalization varied inversely with the time interval between hospitalization and randomization. Rates were higher for patients with HF and reduced ejection fraction within each category. Event rates for those with HF with preserved ejection fraction and a HF hospitalization in the 6 months before randomization were comparable with the rate in patients with HF and reduced ejection fraction with no previous HF hospitalization.

Conclusions—
Rates of cardiovascular death or HF hospitalization are greatest in those who have been previously hospitalized for HF. Independent of EF, rates of death and readmission decline as time from HF hospitalization to trial enrollment increased. Recent HF hospitalization identifies a high-risk population for future clinical trials in HF and reduced ejection fraction and HF with preserved ejection fraction.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00634400.