bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute Autonomic Engagement Assessed by Heart Rate Dynamics During Vagus Nerve Stimulation in Patients With Heart Failure in the ANTHEM‐HF Trial
Authors: NEARING BRUCE D. , LIBBUS IMAD , AMURTHUR BADRI , KENKNIGHT BRUCE H. , VERRIER RICHARD L. 
Published: May 2016

Acute Heart Rate Dynamics During VNSBackgroundChronic vagus nerve stimulation (VNS) applied to produce biomimetic levels of parasympathetic activation is feasible, well tolerated, safe, improves left ventricular ejection fraction, NYHA class, heart rate variability, and baroreflex function, and reduces T‐wave alternans (TWA) in patients with chronic heart failure. However, the acute effects of VNS on beat‐to‐beat heart rate dynamics have not been systematically characterized in humans.Methods and ResultsWe evaluated acute effects of VNS on R‐R‐interval dynamics during the VNS titration period in patients (n = 59) enrolled in ANTHEM‐HF trial by quantifying effects during continuous cyclic VNS (14‐seconds on‐time, 66‐seconds off‐time) adjusted to the maximum tolerable dose without excessive (<4 bpm) bradycardia during the 10‐week titration period. VNS elicited an immediate change in heart rate that was correlated to VNS current amplitude, pulse width, and frequency. Heart rate decreased more in the 28 patients with right‐sided stimulation (–2.22 ± 0.13 bpm) than in the 31 patients with left‐sided stimulation (–0.60 ± 0.08 bpm, P < 0.001). The linear correlation between stimulus intensity and lengthening of the R–R interval was stronger among the 28 patients with right‐sided VNS implantation (r = 0.88, P < 0.0001) than among the 31 patients with left‐sided VNS implantation (r = 0.49, P < 0.002). In all patients, the heart rate change elicited by VNS was significantly greater than the change during the same timing intervals in 10 randomly selected patients without stimulation (+0.08 ± 0.06 bpm, P < 0.001).ConclusionInstantaneous heart rate change during therapeutic levels of VNS in patients with heart failure indicates consistent modulation of the autonomic nervous system for both left‐ and right‐sided stimulation.
REGIONAL GROWTH, INNOVATION, AND LATENT NONLINEAR EFFECTS
Authors: Sanso‐Navarro Marcos , Vera‐Cabello María 
Published: May 2016

ABSTRACTThis paper studies the link between knowledge, innovation, and growth in European regions using nonparametric methods. Our findings suggest that knowledge inputs and the share of innovative firms have a heterogeneous and nonlinear relationship with growth. This evidence has been exploited to examine the consequences of alternative policies using a counterfactual estimation setup, the results of which imply that increasing the formal knowledge base may be optimal in most regions. Less knowledge and innovation intensive regions will also benefit from a higher innovation potential and from a trustworthy and entrepreneurial economic environment.
Constipation prophylaxis in children undergoing orthopedic surgery: A quasi‐experimental study
Authors: Mantegazzi Laila Sara , Seliner Brigitte , Imhof Lorenz 
Published: May 2016

AbstractPurposeThis study evaluated the effectiveness of constipation prophylaxis administered with the support of an advanced practice nurse.DesignA quasi‐experimental study with a historical control group of 112 pediatric (age 1–18) orthopedic patients and an intervention group of 59 patients was conducted in a surgical ward in Switzerland.ResultsThe implementation of a standardized constipation prophylaxis led to an absolute risk reduction (27%) of constipation. Fisher's exact test showed a significant difference in the prevalence of constipation in the two samples, p = .001.Practice ImplicationsConstipation prophylaxis is a necessity in pediatric orthopedics.
Elevated levels of circulating CDH5 and FABP1 in association with human drug‐induced liver injury
Authors: Mikus Maria , Drobin Kimi , Gry Marcus , Bachmann Julie , Lindberg Johan , Yimer Getnet , Aklillu Eleni , Makonnen Eyasu , Aderaye Getachew , Roach James , Fier Ian , Kampf Caroline , Göpfert Jens , Perazzo Hugo , Poynard Thierry , Stephens Camilla , Andrade Raúl J. , Lucena M Isabel , Arber Nadir , Uhlén Mathias , Watkins Paul B. , Schwenk Jochen M. , Nilsson Peter , Schuppe‐Koistinen Ina 
Published: May 2016

AbstractBackground & AimsThe occurrence of drug‐induced liver injury (DILI) is a major issue in all phases of drug development. To identify novel biomarker candidates associated with DILI, we utilised an affinity proteomics strategy, where antibody suspension bead arrays were applied to profile plasma and serum samples from human DILI cases and controls.MethodsAn initial screening was performed using 4594 randomly selected antibodies, representing 3450 human proteins. Resulting candidate proteins together with proposed DILI biomarker candidates generated a DILI array of 251 proteins for subsequent target analysis and verifications. In total, 1196 samples from 241 individuals across four independent cohorts were profiled: healthy volunteers receiving acetaminophen, patients with human immunodeficiency virus and/or tuberculosis receiving treatment, DILI cases originating from a wide spectrum of drugs, and healthy volunteers receiving heparins.ResultsWe observed elevated levels of cadherin 5, type 2 (CDH5) and fatty acid‐binding protein 1 (FABP1) in DILI cases. In the two longitudinal cohorts, CDH5 was elevated already at baseline. FABP1 was elevated after treatment initiation and seemed to respond more rapidly than alanine aminotransferase (ALT). The elevations were verified in the DILI cases treated with various drugs. In the heparin cohort, CDH5 was stable over time whereas FABP1 was elevated.ConclusionsThese results suggest that CDH5 may have value as a susceptibility marker for DILI. FABP1 was identified as a biomarker candidate with superior characteristics regarding tissue distribution and kinetics compared to ALT but likely with limited predictive value for the development of severe DILI. Further studies are needed to determine the clinical utility of the proposed markers.
Using triage for environmental remediation in Antarctica
Authors: Raymond Tania C. , Snape Ian 
Published: May 2016

AbstractRemediation of sites impacted by human activity in Antarctica is a difficult and resource intensive process. With increasing activity and climate change, the extent of damage from human activities is expected to increase and it will not be feasible to protect the environment entirely. We recommend a triage process be used to provide informed and transparent management decisions for comprehensive and adequate environmental remediation in Antarctica. We provide examples that demonstrate realistic outcomes where we have avoided tying up resources on disturbed sites that will recover naturally, are stable, or too damaged to recover, and that also incorporate feasible operational practices. Not all disturbed sites will be remediated and many of those that are, are unlikely to be returned to pristine condition. The decisions around remediation are not based solely on the desired environmental outcome. In the absence of effective legal obligation, we recognize that financial, social, policy, health and safety, technological confidence, and operational feasibility are part of the decision‐making process.
Progressive multifocal leukoencephalopathy after liver transplantation can have favorable or unfavorable outcome
Authors: Dumortier J. , Guillaud O. , Bosch A. , Coppéré B. , Petiot P. , Roggerone S. , Vukusic S. , Boillot O. 
Published: May 2016

AbstractProgressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by the JC polyomavirus (JCPyV) in immunocompromised patients, including solid organ transplant recipients. We report 2 cases of PML late after liver transplantation (144 and 204 months) and review the few other published cases. The clinical course of PML is characterized by a rapid progressive neurological decline coinciding with the presence of white matter lesions on magnetic resonance images. No direct antiviral therapy is available against the JCPyV. The prognosis is therefore extremely poor. Restoration of the immune response achieved by tapering or ending the immunosuppressive therapy is the basis of treatment in transplanted patients. One of our patients is alive 3 years after diagnosis after total withdrawal of immunosuppressive therapy. The other presented severe rejection when tapering immunosuppression and died 26 months after diagnosis.
Effect of deploying community health assistants on appropriate treatment for diarrhoea, malaria and pneumonia: quasi‐experimental study in two districts of Zambia
Authors: Biemba Godfrey , Yeboah‐Antwi Kojo , Vosburg Kathryn Bradford , Prust Margaret L. , Keller Brett , Worku Yekoyesew , Zulu Happy , White Emily , Hamer Davidson H. 
Published: May 2016

AbstractObjectiveA critical shortage of human resources for health in Zambia remains a great challenge. In response, the Zambian Ministry of Health developed a national community health assistant (CHA) programme, aiming to create a well‐trained and motivated community‐based health workforce. This study assessed whether CHAs increased treatment rates for diarrhoea, confirmed malaria or pneumonia in the first programme year.MethodsThis study used a quasi‐experimental difference‐in‐difference design, comparing changes in the catchment areas of health posts with CHAs to those without. Baseline and end line household surveys were conducted to measure the proportion of children under 5 years treated for diarrhoea, malaria or pneumonia in the 2 weeks before the survey and immunisation rates and malaria rapid diagnostic test rates.ResultsWe surveyed 2330 women with children under five from the intervention area and 2314 from comparison areas at baseline and end line. Treatment for diarrhoea, malaria or pneumonia increased by 18.0% (P < 0.01) and 23.5% (P < 0.01) in the intervention and comparison groups, respectively, but DID analysis was not significant (P = 0.27). The proportion of fully immunised children grew by 7.5% in the intervention, but shrank by 7.5% in the comparison group (DID: 0.14; 95% CI 0.12–0.16, P < 0.01).ConclusionAlthough we observed no significant difference between the intervention and comparison groups in the DID estimates for the primary outcome, there were significant increases after one year in treatment for all three diseases in the intervention group from baseline to end line and in the proportion of fully immunised children.
Listeria monocytogenes septicemia in an immunocompromised dog
Authors: Pritchard Jessica C. , Jacob Megan E. , Ward Todd J. , Parsons Cameron T. , Kathariou Sophia , Wood Michael W. 
Published: May 2016

AbstractAn 11‐year‐old, male castrated, Boston Terrier was presented to the North Carolina State University College of Veterinary Medicine Small Animal Emergency Service with a 2‐day history of progressive ataxia, left‐sided head tilt, and anorexia. The dog had previously been diagnosed with chronic lymphoid leukemia and suspected immune‐mediated destruction of his bone marrow precursor cells, possibly due to therapy with immunosuppressive dosages of prednisone and azathioprine. During the physical examination, abnormal findings included an increased body temperature and horizontal nystagmus. Diagnostic investigations included a computed tomography (CT) scan, which confirmed bilateral otitis media, and a blood culture, which was positive for Listeria monocytogenes serotype 4b (epidemic clone 1). Upon treatment with ampicillin/sulbactam, enrofloxacin, and minocycline, the dog became normothermic and the neurologic signs improved. L monocytogenes serotype 4b (epidemic clone 1) has been associated with outbreaks of human listeriosis originating from food contamination. Although rare case reports of Listeria spp. infection in dogs exist, an actual infection with the epidemic clone 1 strain has never before been reported in a dog. It should be included in the differential diagnoses in immunocompromised dogs with clinical signs of septicemia.
Biomarker Analyses of Clinical Outcomes in Patients with Advanced Hepatocellular Carcinoma Treated with Sorafenib with or without Erlotinib in the SEARCH Trial
Authors: Zhu Andrew X. , Kang Yoon-Koo , Rosmorduc Olivier , Evans T.R. Jeffry , Santoro Armando , Ross Paul , Gane Edward , Vogel Arndt , Jeffers Michael , Meinhardt Gerold , Peña Carol E.A. 
Published: May 2016

Abstract
Purpose: Sorafenib is the current standard therapy for advanced hepatocellular carcinoma, but validated biomarkers predicting clinical outcomes are lacking. This study aimed to identify biomarkers predicting prognosis and/or response to sorafenib, with or without erlotinib, in hepatocellular carcinoma patients from the phase III SEARCH trial.
Experimental Design: A total of 720 patients were randomized to receive oral sorafenib 400 mg twice daily plus erlotinib 150 mg once daily or placebo. Fifteen growth factors relevant to the treatment regimen and/or to hepatocellular carcinoma were measured in baseline plasma samples.
Results: Baseline plasma biomarkers were measured in 494 (69%) patients (sorafenib plus erlotinib, n = 243; sorafenib plus placebo, n = 251). Treatment arm–independent analyses showed that elevated hepatocyte growth factor [HGF; HR, 1.687 (high vs. low expression); endpoint multiplicity adjusted (e-adj) P = 0.0001] and elevated plasma VEGFA (HR, 1.386; e-adj P = 0.0377) were significantly associated with poor overall survival (OS) in multivariate analyses, and low plasma KIT [HR, 0.75 (high vs. low); P = 0.0233; e-adj P = 0.2793] tended to correlate with poorer OS. High plasma VEGFC independently correlated with longer TTP (HR, 0.633; e-adj P = 0.0010) and trended toward associating with improved disease control rate (univariate: OR, 2.047; P = 0.030; e-adj P = 0.420). In 67% of evaluable patients (339/494), a multimarker signature of HGF, VEGFA, KIT, EPGN, and VEGFC correlated with improved median OS in multivariate analysis (HR, 0.150; P &lt; 0.00001). No biomarker predicted efficacy from erlotinib.
Conclusions: Baseline plasma HGF, VEGFA, KIT, and VEGFC correlated with clinical outcomes in hepatocellular carcinoma patients treated with sorafenib with or without erlotinib. These biomarkers plus EPGN constituted a multimarker signature for improved OS. Clin Cancer Res; 22(19); 4870–9. ©2016 AACR.
Protection against HPV-16–Associated Tumors Requires the Activation of CD8+ Effector Memory T Cells and the Control of Myeloid-Derived Suppressor Cells
Authors: Diniz Mariana O. , Sales Natiely S. , Silva Jamile R. , Ferreira Luís Carlos S. 
Published: May 2016

Abstract
Active anticancer immunotherapeutic approaches have been shown to induce cellular or humoral immune responses in patients, but, thus far, the observed outcomes did not ensure their recommendation for clinical use. The induction of tumor-specific CD8+ T cells, although required for the clearance of most solid tumors, was shown to be insufficient for the development of a successful immunotherapeutic approach. The suppressive immune environment triggered by tumors, including the expansion of myeloid-derived suppressor cells (MDSC), is detrimental to the development of antitumor immune responses and precludes the generation of more promising clinical outcomes. In this work, we characterized the CD8+ T-cell population specifically involved in the control of tumor growth and the role of MDSCs after administration of an antitumor therapeutic DNA vaccine targeting human papillomavirus type 16 (HPV-16)-associated tumors. Activation of cytotoxic high-avidity CD8+ T cells with an effector memory phenotype was found in mice grafted with tumor cells expressing the HPV-16 oncoproteins. In addition, MDSC antibody depletion further enhanced the immunotherapeutic effects of the vaccine, resulting in the complete eradication of tumor cells. Collectively, the current results indicate that the simultaneous control of MDSCs and activation of high-avidity tumor-specific effector memory CD8+ T cells are key features for tumor protection by immunotherapeutic approaches and deserve further testing under clinical conditions. Mol Cancer Ther; 15(8); 1920–30. ©2016 AACR.
The Mystical Body Falling Apart?
Authors: Rouwhorst Gerard 
Published: May 2016

This article deals with some important changes that occurred in the ritual of the Eucharist and its theological interpretation between Late Antiquity and the twelfth and thirteenth centuries. These had been studied especially by Henri de Lubac in his book Corpus Mysticum. It is quite common – especially among liturgical historians – to present these processes in a purely negatively light and to interpret them in terms of liturgical decline and disintegration, in particular emphasizing the purported loss of the communal, ecclesial character of the Eucharist. This view has been criticized persuasively by other historians (Gary Macy; Eamon Duffy). While taking this criticism seriously, an attempt is made to sketch a differentiated picture of these developments. Making use in particular of mediaeval liturgical commentaries that have received relatively little attention in research, it is argued that the developments are illustrative of some processes which, according to Philip Sheldrake, profoundly affected the approach to spiritual life in the eleventh and twelfth centuries and attest a remarkable reconfiguration in the relations between liturgy, theology and spirituality.
On the Upstream Track Deflection of Tropical Cyclones Past a Mountain Range: Idealized Experiments
Authors: Huang Ching-Yuang , Chen Chien-An , Chen Shu-Hua , Nolan David S. 
Published: May 2016

Abstract
Upstream track deflection of a propagating cyclonic vortex past an isolated mountain range is investigated by using idealized simulations with both boundary layer turbulent mixing and cloud effects. The westbound vortex past a shorter mountain range may experience an earlier northward deflection prior to landfall. The vortex then takes a sudden southward turn as it gets closer to the mountain range, in response to the effects of the stronger northerly wind over the mountain due to the effects of channeling flow. The vortex may deflect southward when approaching a longer mountain range and then rebound northward upstream of the mountain ridge. The southward deflection is primarily induced by the convergence (stretching) effect due to the combination of the speedy core at the southwestern flank of the vortex and a northerly jet between the vortex and the mountain. The vortex then rebounds northward to pass over the mountain as the speedy core rotates counterclockwise to the eastern flank of the vortex. The track deflection near the mountain is also affected as either of both physics is deactivated.
Sensitivity experiments show that for a given steering flow and mountain height, a linear relationship exists between the maximum upstream deflection distance and the nondimensional parameter Rmw/Ly, where Rmw is the vortex size (represented by the radius of the maximum wind) and Ly is the north–south length scale of the mountain. The southward deflection distance increases with smaller Rmw/Ly and higher mountains for both weaker and stronger steering flow. When the steering-flow intensity is doubled, the southward deflection is roughly reduced by 50%.
Lymph Node Density in Node‐Positive Laryngeal Carcinoma
Authors: Imre Abdulkadir , Pinar Ercan , Dincer Elif , Ozkul Yılmaz , Aslan Hale , Songu Murat , Tatar Bekir , Onur Irem , Ozturkcan Sedat , Aladag Ibrahim 
Published: May 2016

ObjectiveWe investigated the value of lymph node density (LND) as a predictor of survival in patients with laryngeal squamous cell carcinoma (SCC) and positive neck node (pN+) after laryngectomy.Study DesignCase series with chart review.SettingKatip Celebi University Ataturk Training and Research Hospital, Izmir, Turkey.Subjects and MethodsWe reviewed the records of 289 patients with newly diagnosed primary laryngeal carcinomas who underwent partial or total laryngectomy and combined neck dissection at a tertiary referral center between June 2006 and December 2014. Patients with pN+ laryngeal SCC (n = 101) were included in the study. Overall survival (OS) and disease‐free survival (DFS) were used to evaluate the prognostic significance of LND.ResultsIn 101 patients with pN+ laryngeal SCC, LND ≥0.09 and number of metastatic lymph nodes >4 were significantly associated with OS and DFS but not the overall tumor, node, and metastasis stage. Forward stepwise Cox regression analysis revealed that LND ≥0.09 was the only independent predictor of both DFS and OS. Furthermore, the odds ratio of LND ≥0.09 was 10 times higher in patients with regional recurrence when compared patients without regional recurrence.ConclusionsLND was the only independent prognostic predictor of OS and DFS in patients with pN+ laryngeal SCC. Moreover, patients with LND ≥0.09 were significantly associated with high risk of regional recurrence. Thus, patients with LND ≥0.09 are at high risk of regional recurrence and death and may be considered for adjuvant chemoradiation.
Seven steps towards a PhD in psychiatry
Authors: Molina-Ruiz Rosa María 
Published: May 2016

Objectives: The present review aims to describe the main steps for completing a psychiatric PhD thesis with success. Methods: A selective review of the literature and the author’s experience as a psychiatrist completing a PhD. Results: Deciding upon a topic, choosing a mentor, organising your time, persevering and remaining motivated are the key elements. Conclusions: Preparedness and diligence lead the way towards a PhD. This advice is also relevant for those undertaking research at any stage of their career.
A Case of Auricular Pseudocyst
Authors: Cohen Vanessa , Fortier-Riberdy Geneviève , Saliba Issam , Davar Sandra 
Published: May 2016

Background: Auricular pseudocyst is a rare, asymptomatic, cystic-like swelling of the auricle that may pose a diagnostic challenge to the clinician. If inadequately treated, recurrences and ear deformities may ensue. Objective: The authors present a case of auricular pseudocyst in a previously healthy 43-year-old man. Aetiologies, histology, differential diagnosis, and treatment modalities are discussed.
Speed bumps on the road to a chemotherapy-free world for lymphoma patients
Authors: Cheson Bruce D. 
Published: May 2016

AbstractWith the increasing number of targeted agents for the treatment of patients with lymphoid malignancies comes the promise of safe and effective chemotherapy-free treatment strategies. A number of single agents, such as ibrutinib and idelalisib, have demonstrated impressive efficacy with a favorable toxicity profile. The observations that most responses are, however, partial and treatment duration is indefinite have stimulated interest in combinations of these agents with chemotherapy as well as with each other. Despite the promise of this approach, several recent trials of combinations of agents have been terminated as the result of life-threatening and fatal complications. Such outcomes have generated a cautionary note of the potential for unforeseen adverse effects that challenge drug development and mitigate against the empiric combination of such drugs outside of a clinical trial setting.
Transformation of the Role of the Auxiliary Staff in Modern Universities
Authors: Сахарова  , Sakharova N. 
Published: May 2016

The article analyzes the key factors of infl uence of external and internal environment on the functioning of Russian higher education institutions, ways to improve
the competitiveness of modern universities in the face of increasing global competition in the education market, reviews the activities of the Government to ensure
the achievement of the strategic objectives of the Russian Federation development for the period up to 2020 in higher education, defi nes trends in requirements for
the competences of certain categories of university staff , provides data on the auxiliaries staff of universities across the country, discusses diff erent points of view on
the role of auxiliaries staff in the university functioning, identifi es the main control problems of auxiliaries staff.