bluuebunny/crossref_metadata_2025 huggingface dataset:
Thermal and crystallization histories of magmatic bodies by Monte Carlo inversion of Mg-Fe isotopic profiles in olivine
Authors: Kin I Sio Corliss , Dauphas Nicolas
Published: November 2016

A random search modeling approach is introduced to retrieve the thermal histories of magmatic bodies from chemical and isotopic analyses of olivine crystals. The sample used for demonstration is an olivine phenocryst from Kilauea Iki lava lake, Hawaii. Random time-temperature (t-T) paths were used to model diffusion accompanying crystal growth. Although a large number of t-T paths yielded acceptable fits to the Mg/Fe chemical profiles measured in olivine, only a small fraction resulted in acceptable fits to the Mg-Fe isotopic profiles. The best-fit cooling path was close to the independently inferred cooling history of this sample. Use of isotopic profiles in minerals coupled with a random search method can be a powerful tool for recovering thermal histories of rocks with little geologic context.
Electron microscopy reveals evidence for simple multicellularity in the Proterozoic fossil Chuaria
Authors: Tang Qing , Pang Ke , Yuan Xunlai , Xiao Shuhai
Published: November 2016

Multicellularity arose multiple times in the evolutionary history of eukaryotes, and simple multicellularity may have a deep history tracing back to the Paleoproterozoic. However, complex multicellular organisms with cellular and tissue differentiation did not appear in the fossil record until the Mesoproterozoic, and it is not until the Ediacaran Period (635–541 Ma) when diverse assemblages of complex multicellular eukaryotes evolved. In the intervening Tonian Period (ca. 1000–720 Ma), the fossil record of multicellular organisms is poorly documented. To address this knowledge gap, we investigated Chuaria and associated carbonaceous compression fossils from the Tonian Liulaobei Formation in North China. These fossils have been variously interpreted as unicellular or multicellular organisms. Our analysis using backscattered-electron scanning electron microscopy (BSE-SEM) revealed direct evidence for simple multicellularity in some of these fossils and suggests that Chuaria may have had a multicellular vegetative stage in its life cycle. This study demonstrates that BSE-SEM has the potential to unveil the hidden diversity of multicellular organisms in the Tonian Period, thus enriching our knowledge about the multiple origins of multicellularity in this critical geological period before Cryogenian glaciations.
Bladder explosion, a rare complication following transurethral resection of the prostate
Authors: Lo Ing-Shiang , Huang Tsung-Yi
Published: November 2016

We present a man aged 69 years who suffered from bladder explosion during transurethral resection of the prostate. Exploratory laparotomy was performed and the bladder was primarily repaired with running sutures. This patient was discharged without symptoms of urinary dysfunction on day 8 after operation. We provide prevention methods that can decrease the risk of this important complication.
Extensive biatrial thrombus straddling the patent foramen ovale and traversing into the left and right ventricle
Authors: Sattar Adil , Win Theingi Tiffany , Schevchuck Alex , Achrekar Abinash
Published: November 2016

We report an extremely rare case of an extensive biatrial thrombus straddling a patent foramen ovale (PFO) extending into the bilateral ventricles in a patient presenting with an acute embolic stroke. Our patient further developed a massive saddle pulmonary embolus (PE) with haemodynamic instability during the course of his hospitalisation. The risks of pharmacological thrombolysis or surgical thrombectomy for PE in a haemodynamically unstable patient with recent embolic stroke posed a significant therapeutic dilemma. Ultimately, the decision was made to continue anticoagulation with unfractionated heparin followed by oral Coumadin. The patient responded well to therapy and at 1-month follow-up, a complete resolution of the thrombus was documented on transoesophageal echocardiogram with full clinical recovery of the patient.
Neonatal osteomyelitis of the first rib causing lung abscess
Authors: John Sijo K , Payyanur Thotan Sundeep , Kumar Vijay , Prabhu Santosh
Published: November 2016

Rib osteomyelitis (OM) is a rare disease that occurs in ∼1% or less of all haematogenous OM. Acute OM of the rib has rarely been reported and its treatment is difficult. Prompt recognition and aggressive treatment will reduce mortality and morbidity in a new born.
Incidental finding of giant pericardial lipoma
Authors: Salim Handi , Anand Dhakshinamurthy Vijay , Watkin Richard , Tapp Luke
Published: November 2016

We describe a patient with an incidental finding of a large mass adjacent to the heart detected on a screening CT scan. The differential diagnosis included primary and secondary tumours of the heart. Subsequent investigation with trans-thoracic echocardiogram and cardiac MRI confirmed a diagnosis of a giant pericardial lipoma, one of the common benign primary cardiac tumours.
Brief episodes of non-specific psychosis later diagnosed as periodic catatonia
Authors: Tang Victor Mark , Park Helen
Published: November 2016

A 73-year-old woman was known to have discrete episodes of psychosis not otherwise specified that would require a brief admission to hospital and total remission following a short course of benzodiazepine or antipsychotic treatment. She had no underlying schizophrenic or affective disorder and was completely unimpaired in between episodes, which could last several years. She presented to us with psychotic symptoms but also noted to have many catatonic features, which were also present on previous presentations. Following failure with antipsychotic trials on this index presentation, she completely remitted with a short course of electroconvulsive therapy. We discuss the importance of identifying and treating catatonia and the lesser-known variant of periodic catatonia. Current presentations should always take into account the lifetime context of psychiatric illness. Rarely do patients with primary psychotic disorders not have any impairment or treatment in between episodes.
Ultrasound imaging to tailor the treatment of acute shoulder pain: a randomised controlled trial in general practice
Authors: Ottenheijm Ramon P G , Cals Jochen W L , Winkens Bjorn , Weijers René E , de Bie Rob A , Dinant Geert-Jan
Published: November 2016

Objective

To determine the clinical effectiveness of ultrasound tailored treatment in patients with acute subacromial disorders.

Design

Pragmatic randomised controlled trial.

Setting

Dutch general practice.

Participants

Patients aged 18–65 years with acute (duration <3 months) unilateral shoulder pain and no previous treatment, in whom the general practitioner suspected a subacromial disorder was enrolled.

Interventions

All patients underwent ultrasound imaging of the affected shoulder. Patients who were still symptomatic after a qualification period of 2 weeks with standard treatment were randomised to treatment tailored to ultrasound diagnosis (disclosure of the ultrasound diagnosis) or usual care (non-disclosure of the ultrasound diagnosis).

Primary outcome measure

Patient-perceived recovery using the Global Perceived Effect questionnaire at 1 year.

Results

129 patients were included. 18 patients recovered during the 2-week qualification period, resulting in 111 randomised patients; 56 were allocated to ultrasound tailored treatment and 55 to usual care. After 1 year, no statistically significant differences in recovery were found between the ultrasound tailored treatment group (72.5% (37/51)) and the usual care group (60% (30/50), OR 2.24 (95% CI 0.72 to 6.89; p=0.16)). Also, healthcare use was similar.

Conclusions

This study has shown no clinically significant difference in the primary outcome measure between the ultrasound tailored treatment and usual care groups. Furthermore, there was no overall difference in healthcare resources used between groups. Although no formal cost data are included, one can only assume that the ultrasound examinations are additional costs for the intervention group, which cannot be justified in routine practice based on this trial. Based on this study, no change in current pragmatic guidelines to incorporate early ultrasound imaging can be recommended.

Trial registration number

NTR2403; Results.
Reporting quality of abstracts of trials published in top five pain journals: a protocol for a systematic survey
Authors: Sriganesh Kamath , Bharadwaj Suparna , Wang Mei , Abbade Luciana P F , Couban Rachel , Mbuagbaw Lawrence , Thabane Lehana
Published: November 2016

Introduction

Abstracts of randomised controlled trials (RCTs) are often the first and the only source read in a journal by busy healthcare providers. This necessitates good reporting of abstracts. The quality of reporting of abstracts, though gradually improving over time, is still not uniform across medical journals. Improvement in completeness of reporting of abstracts has been documented in general medical journals after the publication of the consolidated standards of reporting trials (CONSORT) extension for abstracts in 2008. Currently, this aspect has not been assessed with regards to pain journals. This study aims to compare the completeness of reporting of abstracts before and after the publication of CONSORT statement for abstracts in five pain journals.

Methods and analyses

The abstracts of RCTs published from 1 January 2005 to 31 December 2007 (pre-CONSORT) and from 1 January 2013 to 31 December 2015 (post-CONSORT) will be assessed for the quality of reporting. Studies without abstracts, non-English abstracts, abstracts not reporting on RCTs or on humans and conference abstracts will be excluded. A thorough search of MEDLINE will be carried out in April 2016. All identified studies will be screened for inclusion based on titles and abstracts. Data will be extracted by two sets of independent reviewers for each abstract in duplicate regarding compliance with CONSORT statement for abstracts. Full-text review will be performed to obtain additional characteristics which are likely to affect reporting quality. The unadjusted and adjusted differences in the mean number of items reported will be analysed using a two sample t-test and generalised estimation equation in SPSS.

Ethics and dissemination

As far as we know, this is the first study to evaluate reporting quality of abstracts of pain journals based on CONSORT extension for abstracts. The findings of this study will be disseminated by a presentation at a conference and through publication in a peer-reviewed journal. Ethics committee approval was not sought for this survey.
The importance of high-precision hadronic calorimetry to physics
Authors: Hauptman John
Published: November 2016

The reconstruction and high-precision measurement of the four-vectors of [Formula: see text] and [Formula: see text] decays to quarks, which constitute nearly 70% of their decay branching fractions, are critical to a high efficiency and high quality experiment. Furthermore, it is crucial that the energy resolution, and consequently the resolution on the invariant mass of the two fragmenting quarks, is comparable to the energy–momentum resolution on the other particles of the standard model, in particular, electrons, photons, and muons, at energies around 100 GeV. I show that this “unification of resolutions” on all particles of the standard model is now in sight, and will lead to excellent physics at an electron–positron collider.
A family of bi-orderable non-fibered 2-bridge knot groups
Authors: Yamada Takafumi
Published: November 2016

We give a new infinite family of non-fibered 2-bridge knots whose knot groups are bi-orderable.
Theoretical prediction of probable isotopes of superheavy nuclei of Z = 122
Authors: Manjunatha H. C.
Published: November 2016

We have studied the [Formula: see text]-decay half-life and spontaneous fission half-lives of isotopes of superheavy element [Formula: see text] in the range [Formula: see text]. A comparison of calculated alpha half-lives with the literature [D. N. Poenaru, R. A. Gherghescu and W. Greiner, Phys. Rev. C 83 (2011) 014601, D. N. Poenaru, R. A. Gherghescu and W. Greiner, Phys. Rev. C 85 (2012) 034615] and the analytical formulas of Royer [G. Royer, J. Phys. G; Nucl. Part. Phys. 26 (2000) 1149] shows good agreement with each other. To identify the mode of decay of these isotopes, the spontaneous-fission half-lives were also evaluated using the semiempirical relation given by [C. Xu, Z. Ren and Y. Guo, Phys. Rev. C 78 (2008) 044329]. A comparative study on the competition of alpha decay versus spontaneous fission of superheavy nuclei (SHN) reveals that around eight isotopes ([Formula: see text]122) survive fission and have alpha decay channel as the prominent mode of decay and hold the possibility to be synthesized in the laboratory. The alpha decay half-lives and spontaneous fission half-lives of SHN with [Formula: see text], [Formula: see text]–306, with [Formula: see text], [Formula: see text]–300, and with [Formula: see text], [Formula: see text]–297 are also studied. The present study will be useful in the synthesis of superheavy elements [Formula: see text] by using the actinide based reactions with stable projectiles heavier than [Formula: see text]Ca.
Introducing rigid π-conjugated peripheral substituents in phthalocyanines for DSSCs
Authors: Tejerina Lara , Caballero Esmeralda , Martínez-Díaz M. Victoria , Nazeeruddin Mohammad Khaja , Grätzel Michael , Torres Tomas
Published: November 2016

A new carboxy-Zn(II)phthalocyanine bearing rigid 2,6-diarylphenyl peripheral substituents linked to the macrocycle through alkynyl spacers has been prepared by a convergent approach, which implies a triple Sonogashira coupling between the formyltriiodoZnPc and the corresponding terminal alkyne. Indeed, the introduction of this type of [Formula: see text]-conjugated peripheral substituents accounts for a remarkable red shift of the phthalocyanine Q-band until ca. 700 nm. However, aggregation phenomena could not be supressed and may explain the moderate overall efficiencies achieved with these devices.
Collaborative Cloud Manufacturing: Design of Business Model Innovations Enabled by Cyberphysical Systems in Distributed Manufacturing Systems
Authors: Rauch Erwin , Seidenstricker Sven , Dallasega Patrick , Hämmerl Robert
Published: November 2016

Collaborative cloud manufacturing, as a concept of distributed manufacturing, allows different opportunities for changing the logic of generating and capturing value. Cyberphysical systems and the technologies behind them are the enablers for new business models which have the potential to be disruptive. This paper introduces the topics of distributed manufacturing as well as cyberphysical systems. Furthermore, the main business model clusters of distributed manufacturing systems are described, including collaborative cloud manufacturing. The paper aims to provide support for developing business model innovations based on collaborative cloud manufacturing. Therefore, three business model architecture types of a differentiated business logic are discussed, taking into consideration the parameters which have an influence and the design of the business model and its architecture. As a result, new business models can be developed systematically and new ideas can be generated to boost the concept of collaborative cloud manufacturing within all sustainable business models.
An Adaptive Information Quantity-Based Broadcast Protocol for Safety Services in VANET
Authors: Wang Wenjie , Luo Tao , Hu Ying
Published: November 2016

Vehicle-to-vehicle communication plays a significantly important role in implementing safe and efficient road traffic. When disseminating safety messages in the network, the information quantity on safety packets changes over time and space. However, most of existing protocols view each packet the same to disseminate, preventing vehicles from collecting more recent and precise safety information. Hence, an information quantity-based broadcast protocol is proposed in this paper to ensure the efficiency of safety messages dissemination. In particular, we propose the concept of emergency-degree to evaluate packets’ information quantity. Then we present EDCast, an emergency-degree-based broadcast protocol. EDCast differentiates each packet’s priority for accessing the channel based on its emergency-degree so as to provide vehicles with more safety information timely and accurately. In addition, an adaptive scheme is presented to ensure fast dissemination of messages in different network condition. We compare the performance of EDCast with those of three other representative protocols in a typical highway scenario. Simulation results indicate that EDCast achieves higher broadcast efficiency and less redundancy with less delivery delay. What we found demonstrates that it is feasible and necessary for incorporating information quantity of messages in designing an efficient safety message broadcast protocol.
The Multiobjective Constraint Fault-Tolerant Control of Event-Triggered Nonuniform Transmission for Networked T-S Fuzzy System
Authors: Li Ya-jie , Li Wei
Published: November 2016

Considering the actuator saturation, the problem of multiobjective constraint fault-tolerant control is studied for networked Takagi-Sugeno (T-S) fuzzy system with nonuniform transmission period under the discrete event-triggered communication scheme (DETCS). A closed-loop T-S fuzzy model, which includes numerous factors such as actuator saturation, actuator failure, event-triggered condition, nonuniform transmission period, and time-delay, is established by transferring the effect caused by the nonuniform update period on the system performance into the effect on the system time-delay. Two stability criterions and two codesign methods for the networked closed-loop failure T-S fuzzy system are developed based on a discontinuous Lyapunov-Krasovskii function, a kind of reciprocally convex technology, a kind of linear convex combination, Jessen inequality, and Wirtinger’s inequality. A feasible experimental solution is presented to verify the effectiveness of the proposed method.
Investigation of Antileishmanial Activities of Acridines Derivatives against Promastigotes and Amastigotes Form of Parasites Using Quantitative Structure Activity Relationship Analysis
Authors: Chtita Samir , Ghamali Mounir , Hmamouchi Rachid , Elidrissi Bouhya , Bourass Mohamed , Larif Majdouline , Bouachrine Mohammed , Lakhlifi Tahar
Published: November 2016

In a search of newer and potent antileishmanial (against promastigotes and amastigotes form of parasites) drug, a series of 60 variously substituted acridines derivatives were subjected to a quantitative structure activity relationship (QSAR) analysis for studying, interpreting, and predicting activities and designing new compounds by using multiple linear regression and artificial neural network (ANN) methods. The used descriptors were computed with Gaussian 03, ACD/ChemSketch, Marvin Sketch, and ChemOffice programs. The QSAR models developed were validated according to the principles set up by the Organisation for Economic Co-operation and Development (OECD). The principal component analysis (PCA) has been used to select descriptors that show a high correlation with activities. The univariate partitioning (UP) method was used to divide the dataset into training and test sets. The multiple linear regression (MLR) method showed a correlation coefficient of 0.850 and 0.814 for antileishmanial activities against promastigotes and amastigotes forms of parasites, respectively. Internal and external validations were used to determine the statistical quality of QSAR of the two MLR models. The artificial neural network (ANN) method, considering the relevant descriptors obtained from the MLR, showed a correlation coefficient of 0.933 and 0.918 with 7-3-1 and 6-3-1 ANN models architecture for antileishmanial activities against promastigotes and amastigotes forms of parasites, respectively. The applicability domain of MLR models was investigated using simple and leverage approaches to detect outliers and outsides compounds. The effects of different descriptors in the activities were described and used to study and design new compounds with higher activities compared to the existing ones.
Experimental Studies on the Bonding Strength and Fracture Behavior of Incompatible Materials Bonded by Mechanical Adhesion in Multilayer Rotational Molding
Authors: Löhner Martin , Drummer Dietmar
Published: November 2016

Rotational molding is a plastic processing method that allows for the production of seamless, hollow parts. Defined shaping of the polymeric material only takes place on the outer surface where contact to the tooling is given. The inner surface forms by surface tension effects. By sequential adding of materials, complex multilayer build-up is possible. Besides pure, single materials, filled, or multiphase systems can be processed as well. In this work, possibilities to generate bonding between supposedly incompatible materials by adding a mix-material interlayer are investigated. Interlock mechanisms on a microscale dimension occur and result in mechanical bonding between the used materials, polyethylene (PE) and thermoplastic polyurethane (TPE-U). The bonding strength between the materials was investigated to reveal the correlations between processing parameters, resulting layer build-up, and bonding strength. The failure behavior was analyzed and inferences to the influence of the varied parameters were drawn.
Indentation Curves in Viscoplastic Alloys: Mathematical Model, Fitting Procedures, and Application to the Room-Temperature Creep of an Al-Sn Alloy
Authors: Jacobo V. H. , Ortiz A. , Schouwenaars R.
Published: November 2016

Hardness is an important design parameter but, in rate-dependent materials, its value depends on the indentation speed and dwell time during measurement. Dimensional analysis for indentation testing provides rigorous descriptions for the load-displacement curves of elastoplastic materials; viscoplastic materials can be treated likewise by neglecting the plastic part of the deformation, which is not accurate for most engineering alloys. This work presents a methodology for constructing model indentation curves taking into account concurrent viscous and plastic strains, as well as corrections for tip roundness, load frame compliance, and the point of first contact. A procedure is presented to calculate the parameters of a single model curve by fitting to multiple experimental curves, incorporating the numerical solutions of the differential equation describing viscoplastic behaviour. The procedure is applied to Vickers indentation in brass and steel calibration blocks and to a SAE783 Al-Sn alloy for journal bearings, where creep at room temperature is observed. The soundness of the approach is demonstrated by the large reduction of statistical uncertainty on the parameters describing the indentation curves. A rate-independent hardness will be found and a brief comment is provided on the comparison between creep analysis by indentation and uniaxial tension.
Testing and Micromechanical Modelling of Rockfill Materials Considering the Effect of Stress Path
Authors: Feng Wang , Shichun Chi , Shijie Li , Yufeng Jia
Published: November 2016

We have extended the micromechanics-based analytical (M-A) model to make it capable of simulating Nuozhadu rockfill material (NRFM) under different stress paths. Two types of drained triaxial tests on NRFM were conducted, namely, the stress paths of constant stress ratio (CSR) and the complex stress paths with transitional features. The model was improved by considering the interparticle parameter variation with the unloading-reloading cycles and the effect of the stress transition path. The evolution of local dilatancy at interparticle planes due to an externally applied load is also discussed. Compared with Duncan-Chang’s E-u and E-B models, the improved model could not only better describe the deformation properties of NRFM under the stress path loading, but also present the volumetric strain changing from dilatancy to contractancy with increasing transitional confining pressures. All simulations have demonstrated that the proposed M-A model is capable of modelling the mechanical behaviour of NRFM in the dam.
Structural Femoral Shaft Allografts for Anterior Spinal Column Reconstruction in Osteoporotic Spines
Authors: Chang Bong-Soon , Jung Jong-Hun , Park Sang-Min , Lee Seung Hoo , Lee Choon-Ki , Kim Hyoungmin
Published: November 2016

This study was to investigate the clinical and radiographical outcomes of anterior spinal column reconstruction using structural femoral shaft allografts in osteoporotic patients. Retrospective analyses of medical records, radiographic parameters, and postoperative complications were performed in twenty-one patients who underwent anterior spinal column reconstruction surgery for osteoporotic vertebral collapse or nonunion. Surgical invasiveness, clinical outcomes, postoperative complications, and radiographic outcomes were evaluated. Ambulatory status and back pain significantly improved. The Cobb’s angle of segmental kyphosis significantly improved immediately after surgery with slight progression at the final follow-up. There were two cases of failed reconstruction with marked progression of kyphosis; both were related to loosening of screws rather than subsidence of the graft. Anterior spinal column reconstruction using femoral shaft allografts improved kyphosis and resulted in minimal subsidence and therefore is recommended as an effective treatment option for dealing with osteoporotic vertebral collapse and kyphotic deformity.
Noninvasive Ventilation with Heliox for Respiratory Distress Syndrome in Preterm Infant: A Systematic Review and Meta-Analysis
Authors: Long Chen , Li Wang , Wanwei Li , Jie Li , Yuan Shi
Published: November 2016

Objectives. To assess whether noninvasive ventilation with Heliox reduces the need for endotracheal ventilation and subsequent complications in preterm infants with respiratory distress syndrome (RDS). Methods. A search of major electronic databases, including MEDLINE and the Cochrane Central Register of Controlled Trials, for randomized or quasi-randomized controlled trials that compared noninvasive ventilation with Heliox versus noninvasive ventilation with standard gas for preterm infants with RDS was performed. The primary outcome was the incidence of intubation. The secondary outcomes were the level of PaCO2, the use of surfactant, and other complications. Results. Two randomized and one quasi-randomized controlled trials including 123 preterm infants were assessed. Heliox was found to significantly decrease the incidence of intubation (RR: 0.42; 95% CI: 0.23 to 0.78), the level of PaCO2 (MD: −9.61; 95% CI: −15.76 to −03.45), and the use of surfactant (RR: 0.25; 95% CI: 0.10 to 0.61) as compared with standard gas. No significant differences were found in other secondary outcomes. Conclusions. Noninvasive ventilation with Heliox decreases the incidence of intubation in preterm infants suffering from RDS. However, data on clinical outcomes are limited. Larger trials are needed to verify the beneficial effects.
Context-Based Topology Control for Wireless Mesh Networks
Authors: Mudali Pragasen , Adigun Matthew Olusegun
Published: November 2016

Topology Control has been shown to provide several benefits to wireless ad hoc and mesh networks. However these benefits have largely been demonstrated using simulation-based evaluations. In this paper, we demonstrate the negative impact that the PlainTC Topology Control prototype has on topology stability. This instability is found to be caused by the large number of transceiver power adjustments undertaken by the prototype. A context-based solution is offered to reduce the number of transceiver power adjustments undertaken without sacrificing the cumulative transceiver power savings and spatial reuse advantages gained from employing Topology Control in an infrastructure wireless mesh network. We propose the context-based PlainTC+ prototype and show that incorporating context information in the transceiver power adjustment process significantly reduces topology instability. In addition, improvements to network performance arising from the improved topology stability are also observed. Future plans to add real-time context-awareness to PlainTC+ will have the scheme being prototyped in a software-defined wireless mesh network test-bed being planned.
Adaptive Regulation of a Class of Uncertain Nonlinear Systems with Nonstrict Feedback Form
Authors: Li Jian-xiong , Gao Chong-yi , Fang Yi-ming , Guo Cui , Zhang Wen-bo
Published: November 2016

This paper focuses on the semiglobal stabilization for a class of nonlinear systems with nonstrict feedback form. Based on a generalized scaling technique, an adaptive control algorithm with dynamic high gain is developed for a class of nonstrict feedback nonlinear systems. It can be proved that, under some appropriate design parameters, all signals of the resulting closed-loop system are bounded semiglobally, and the system state will be convergent to origin exponentially. Finally, a numerical simulation is provided to confirm the effectiveness of the proposed method.
Tim-3 Expression on Tumor-Infiltrating PD-1+CD8+ T Cells Correlates with Poor Clinical Outcome in Renal Cell Carcinoma
Authors: Granier Clémence , Dariane Charles , Combe Pierre , Verkarre Virginie , Urien Saïk , Badoual Cécile , Roussel Hélène , Mandavit Marion , Ravel Patrice , Sibony Mathilde , Biard Lucie , Radulescu Camélia , Vinatier Emeline , Benhamouda Nadine , Peyromaure Michael , Oudard Stéphane , Méjean Arnaud , Timsit Marc-Olivier , Gey Alain , Tartour Eric
Published: November 2016

Inhibitory receptors expressed by T cells mediate tolerance to tumor antigens, with coexpression of these receptors exacerbating this dysfunctional state. Using the VectraR automated multiparametric immunofluorescence technique, we quantified intratumoral CD8+ T cells coexpressing the inhibitory receptors PD-1 and Tim-3 from patients with renal cell carcinoma (RCC). A second validation cohort measured the same parameters by cytometry. The percentage of tumor-infiltrating CD8+ T cells coexpressing PD-1 and Tim-3 correlated with an aggressive phenotype and a larger tumor size at diagnosis. Coexpression of PD-1 and Tim-3 above the median conferred a higher risk of relapse and a poorer 36-month overall survival. Notably, other CD8+T-cell subsets did not exert a similar effect on overall survival. Moreover, only the PD-1+Tim-3+ subset of CD8+ T cells exhibited impaired function after stimulation. Our findings establish intratumoral Tim-3+PD1+CD8+ T cells as critical mediators of an aggressive phenotype in RCC. Use of the Vectra tool may be useful to identify similarly critical prognostic and predictive biomarkers in other tumor types and their response to immunotherapy. Cancer Res; 77(5); 1075–82. ©2016 AACR.
Mutational Landscape of Pediatric Acute Lymphoblastic Leukemia
Authors: Ding Ling-Wen , Sun Qiao-Yang , Tan Kar-Tong , Chien Wenwen , Thippeswamy Anand Mayakonda , Eng Juh Yeoh Allen , Kawamata Norihiko , Nagata Yasunobu , Xiao Jin-Fen , Loh Xin-Yi , Lin De-Chen , Garg Manoj , Jiang Yan-Yi , Xu Liang , Lim Su-Lin , Liu Li-Zhen , Madan Vikas , Sanada Masashi , Fernández Lucia Torres , Preethi Hema , Lill Michael , Kantarjian Hagop M. , Kornblau Steven M. , Miyano Satoru , Liang Der-Cherng , Ogawa Seishi , Shih Lee-Yung , Yang Henry , Koeffler H. Phillip
Published: November 2016

Current standard of care for patients with pediatric acute lymphoblastic leukemia (ALL) is mainly effective, with high remission rates after treatment. However, the genetic perturbations that give rise to this disease remain largely undefined, limiting the ability to address resistant tumors or develop less toxic targeted therapies. Here, we report the use of next-generation sequencing to interrogate the genetic and pathogenic mechanisms of 240 pediatric ALL cases with their matched remission samples. Commonly mutated genes fell into several categories, including RAS/receptor tyrosine kinases, epigenetic regulators, transcription factors involved in lineage commitment, and the p53/cell-cycle pathway. Unique recurrent mutational hotspots were observed in epigenetic regulators CREBBP (R1446C/H), WHSC1 (E1099K), and the tyrosine kinase FLT3 (K663R, N676K). The mutant WHSC1 was established as a gain-of-function oncogene, while the epigenetic regulator ARID1A and transcription factor CTCF were functionally identified as potential tumor suppressors. Analysis of 28 diagnosis/relapse trio patients plus 10 relapse cases revealed four evolutionary paths and uncovered the ordering of acquisition of mutations in these patients. This study provides a detailed mutational portrait of pediatric ALL and gives insights into the molecular pathogenesis of this disease. Cancer Res; 77(2); 390–400. ©2016 AACR.
PolyI:C and CpG Synergize with Anti-ErbB2 mAb for Treatment of Breast Tumors Resistant to Immune Checkpoint Inhibitors
Authors: Charlebois Roxanne , Allard Bertrand , Allard David , Buisseret Laurence , Turcotte Martin , Pommey Sandra , Chrobak Pavel , Stagg John
Published: November 2016

Innate and adaptive immune cells play an important role in the therapeutic activity of anti-ErbB2 mAbs, such as trastuzumab. In the clinic, breast tumors poorly infiltrated with immune cells are more resistant to trastuzumab, and patients have a worse prognosis. Because type I and II IFNs are critical to the immune-mediated activity of anti-ErbB2 mAb, we investigated the effect of combining polyI:C and CpG with trastuzumab-like therapy in immunocompetent mouse models of ErbB2+ breast cancer. We demonstrated that in situ delivery of polyI:C and CpG combined to systemic anti-ErbB2 mAb triggered a potent inflammatory response in breast tumors able to induce long-lasting CD8+ T cell–dependent antitumor immunity. Remarkably, polyI:C and CpG was superior to combined PD-1/CTLA-4 blockade in sensitizing tumors to anti-ErbB2 mAb therapy. Local injection of CpG and polyI:C in a primary tumor significantly enhanced the activity of systemic anti-ErbB2 mAb against a distant untreated tumor. Type I and II IFNs, as well as natural killer cells and CD8+ T cells, were indispensible to the synergistic activity of the combination treatment. Because synthetic RNA analogues and CpG oligodeoxynucleotides have been safely used in clinical trials, our study supports combination treatments with anti-ErbB2 mAbs. Cancer Res; 77(2); 312–9. ©2016 AACR.
Plk4 Promotes Cancer Invasion and Metastasis through Arp2/3 Complex Regulation of the Actin Cytoskeleton
Authors: Kazazian Karineh , Go Christopher , Wu Hannah , Brashavitskaya Olga , Xu Roland , Dennis James W. , Gingras Anne-Claude , Swallow Carol J.
Published: November 2016

The polo family serine threonine kinase Plk4 has been proposed as a therapeutic target in advanced cancers based on increased expression in primary human cancers, facilitation of tumor growth in murine xenograft models, and centrosomal amplification induced by its overexpression. However, both the causal link between these phenomena and the feasibility of selective Plk4 inhibition remain unclear. Here we characterize Plk4-dependent cancer cell migration and invasion as well as local invasion and metastasis of cancer xenografts. Plk4 depletion suppressed cancer invasion and induced an epithelial phenotype in poorly differentiated breast cancer cells. In an unbiased BioID screen for Plk4 interactors, we identified members of the Arp2/3 complex and confirmed a physical and functional interaction between Plk4 and Arp2 in mediating Plk4-driven cancer cell movement. This interaction is mediated through the Plk4 Polo-box 1-Polo-box 2 domain and results in phosphorylation of Arp2 at the T237/T238 activation site, which is required for Plk4-driven cell movement. Our results validate Plk4 as a therapeutic target in cancer patients and reveal a new role for Plk4 in regulating Arp2/3-mediated actin cytoskeletal rearrangement. Cancer Res; 77(2); 434–47. ©2016 AACR.
Targeting Cancer Metabolism: Dietary and Pharmacologic Interventions
Authors: Vernieri Claudio , Casola Stefano , Foiani Marco , Pietrantonio Filippo , de Braud Filippo , Longo Valter
Published: November 2016

Most tumors display oncogene-driven reprogramming of several metabolic pathways, which are crucial to sustain their growth and proliferation. In recent years, both dietary and pharmacologic approaches that target deregulated tumor metabolism are beginning to be considered for clinical applications. Dietary interventions exploit the ability of nutrient-restricted conditions to exert broad biological effects, protecting normal cells, organs, and systems, while sensitizing a wide variety of cancer cells to cytotoxic therapies. On the other hand, drugs targeting enzymes or metabolites of crucial metabolic pathways can be highly specific and effective, but must be matched with a responsive tumor, which might rapidly adapt. In this review, we illustrate how dietary and pharmacologic therapies differ in their effect on tumor growth, proliferation, and metabolism and discuss the available preclinical and clinical evidence in favor of or against each of them. We also indicate, when appropriate, how to optimize future investigations on metabolic therapies on the basis of tumor- and patient-related characteristics.

Significance: To our knowledge, this is the first review article that comprehensively analyzes the preclinical and preliminary clinical experimental foundations of both dietary and pharmacologic metabolic interventions in cancer therapy. Among several promising therapies, we propose treatment personalization on the basis of tumor genetics, tumor metabolism, and patient systemic metabolism.Cancer Discov; 6(12); 1315–33. ©2016 AACR.
Impact of Pseudomonas aeruginosa Infection on Respiratory Muscle Function in Adult Cystic Fibrosis Patients
Authors: Magnet Friederike Sophie , Callegari Jens , Dieninghoff Doris , Spielmanns Marc , Storre Jan Hendrik , Schmoor Claudia , Windisch Wolfram
Published: November 2016

Background:Pseudomonas aeruginosa infection impairs respiratory muscle function in adolescents with cystic fibrosis, but its impact on adult patients has not been characterised. Objectives: To investigate respiratory muscle function in adult cystic fibrosis patients according to P. aeruginosa status (repetitive samples over 12 months). Methods: The pressure-time index of the respiratory muscles (PTImus), a measure of their efficiency, served as the primary outcome. In addition, respiratory load and maximal respiratory muscle strength were assessed. Results: In 51 patients examined (65% female; median age 32 years, IQR 24-40), a median of 3.0 (IQR 2-4) different pathogens was found in each patient. The PTImus was 0.113 and 0.126 in Pseudomonas-positive (n = 33) and -negative (n = 18) patients, respectively (p = 0.53). Univariate analysis showed a lower PTImus in male than in female patients (p = 0.006). Respiratory muscle load and strength were otherwise comparable, with the exception of higher nasal sniff pressures in Pseudomonas-positive patients who were chronically infected (>50% of positive samples). Quality of Life (according to the Cystic Fibrosis Questionnaire-Revised) was higher if both respiratory load and the PTImus were low (high respiratory muscle efficiency). Conclusions: Chronic P. aeruginosa infection does not influence respiratory muscle efficiency in adult cystic fibrosis patients with otherwise multiple co-infections. In addition, patients with reduced respiratory muscle efficiency had worse Quality of Life.
ПІСЛЯДИПЛОМНА МЕДИЧНА ОСВІТА – НОВІ ГОРИЗОНТИ Й ПЕРСПЕКТИВИ
Authors: Voronenko Yu. V. , Mintser O. P. , Palahin O. V.
Published: November 2016

Представлено нове розуміння проблем передавання знань, змісту освіти та управління нею. На часі поставлено питання післядипломного додаткового проблемно-орієнтованого навчання, особливо в медицині, що включає такі нові напрями, як полідисциплінарність, мультидисциплінарність та трансдисциплінарність. Виникає необхідність створення єдиного банку контрольно-вимірювальних методик для перевірки залишкових знань не тільки з дисциплін, а й з навчальних модулів. Не менш важливим стає й введення так званої “нелінійної” схеми організації навчального процесу.Розроблення суворої методології трансдисциплінарності наукових досліджень та освіти виявило особливу роль інформатики як елемента її системно-технологічної підтримки, враховуючи системоутворюючу роль сучасної інформатики та інтеграцію інформаційних технологій практично в усі галузі науки й освіти.Запропоновано розділити навчання лікарів і провізорів у стратегії безперервного професійного розвитку в післядипломній медичній освіті на дві частини – базисну та додаткову (трансдицисплінарну, проблемно-орієнтовану) з заданим рівнем компетентності.
РЕАЛЬНІСТЬ ТА ПЕРСПЕКТИВИ ВПРОВАДЖЕННЯ НА СУЧАСНОМУ ЕТАПІ ДИСТАНЦІЙНОГО НАВЧАННЯ У СФЕРУ ОХОРОНИ ЗДОРОВ’Я
Authors: Melnychuk I. M. , Yastremskа S. O.
Published: November 2016

У статті розглянуто можливість і доцільність впровадження дистанційного навчання в медичну освіту. Представлені дані щодо тлумачення змісту, особливостей, переваг та недоліків використання дистанційної форми навчання в медичних навчальних закладах. Відображено сучасний погляд на впровадження дистанційного навчання в медицину та систему медичної освіти. Показано, що сучасні дистанційні технології навчання дають змогу проектувати і створювати інформаційні інструменти, які сприяють засвоєнню теоретичних знань медичної науки для опанування практичної частини зі спеціальності.
РЕФОРМУВАННЯ ВИЩОЇ ОСВІТИ В УКРАЇНІ
Authors: Shukhtin V. V. , Коtiuzhynska S. H. , Lіebіedіevа T. L. , Shukhtina I. M.
Published: November 2016

У статті розглянуті основні правові, організаційні, фінансові засади функціонування системи вищої освіти, які створюють умови для поєднання освіти з наукою та виробництвом з метою підготовки конкурентоспроможного людського капіталу для високотехнологічного та інноваційного розвитку країни, самореалізації особистості, забезпечення потреб суспільства, ринку праці та держави у кваліфікованих фахівцях. Автори статті аналізують ключові проблеми розвитку системи освіти, підвищення якості професійної підготовки фахівців, законодавчого регулювання розвитку системи вищої освіти в Україні в контексті Болонського процесу.  Висвітлено стан і перспективи змін освітньої системи України в аспектах використання та вдосконалення різних засобів забезпечення якості навчального процесу і заключних освітніх кваліфікацій. Розглянуто проблемні фактори функціонування вищої освіти України під кутом зору нагальних потреб модернізації вітчизняного освітнього середовища, тобто приведення його у відповідність до імперативних вимог сучасності. Особлива увага приділяється міжнародному співробітництву в галузі освіти, інтеграції національної освіти до міжнародного освітянського простору.
МЕЖІ СЕРЦЕВОЇ ТУПОСТІ: ПРОТИРІЧЧЯ МІЖ ІСТИНОЮ І КАНОНІЧНИМИ ПРАВИЛАМИ ПЕРКУСІЇ В ПРОПЕДЕВТИЦІ ВНУТРІШНІХ ХВОРОБ
Authors: Buhai B. H. , Andreichyn S. M. , Chernets T. Yu. , Chlek M. V. , Bilkevych N. A. , Ruda M. M. , Vereshchahina N. Ya. , Yarema N. Z. , Kavetska N. A. , Hanberger I. I. , Kucher S. V.
Published: November 2016

У статті викладена необхідність зміни стереотипів щодо канонічних методик перкуторного визначення  меж відносної та абсолютної тупостей серця. Корективи, запропоновані авторами, дозволяють клініцистам біля ліжка хворого уникнути похибки в понад один сантиметр при визначенні верхньої межі серця  за стандартами його відносної та абсолютної тупостей, і внести елементи примирення при інтерпретації різних варіантів його перкусії, що має особливе значення для викладачів кафедр пропедевтики внутрішньої медицини та майбутніх лікарів.
ОРГАНІЗАЦІЯ ПРАКТИЧНОЇ ПІДГОТОВКИ СТУДЕНТІВ-ПРОВІЗОРІВ ПРИ ВИВЧЕННІ ОРГАНІЧНОЇ ХІМІЇ
Authors: Zahrychuk H. Ya. , Demyd A. Ye.
Published: November 2016

У статті розглянуто організацію практичної підготовки студентів фармацевтичного факультету в ДВНЗ “Тернопільський державний медичний університет імені І. Я. Горбачевського МОЗ України” при вивченні органічної хімії. Звернуто увагу на формування загальних компетентностей, зокрема: здатності застосовувати практичні знання у критичних ситуаціях, здатності до адаптації та дій у новій ситуації і здатності до абстрактного мислення, здатності проводити дослідження на сучасному науковому рівні, аналізу та синтезу, вчитися й бути сучасно навченим.
ДЕЯКІ АСПЕКТИ ПЕРВИННОЇ ЕКСПЕРТИЗИ НАУКОВИХ ПРАЦЬ НА НАЯВНІСТЬ АКАДЕМІЧНОГО ПЛАГІАТУ
Authors: Khobzey M. K. , Verhun A. R.
Published: November 2016

За 2015–2016 рр. у Львівському національному медичному університеті імені Данила Галицького впроваджено ряд заходів з протидії академічному плагіату. На факультетах, теоретичних та клінічних кафедрах затверджуються (з числа працівників уні­верситету: штатних викладачів, доцентів, професорів) особи, від­повідальні за перевірку наукових робіт з застосуванням елек­тронних систем програмного забезпечення антиплагіатної екс­пертизи; не можуть призначатися викладачі-сумісники, аспіранти, здобувачі. Рекомендоване програмне за­безпечення визначається та обновлюється науковим відділом. Запроваджено повноцінну поточну перевірку працівниками наукового відділу публікацій та ди­сертаційних робіт на предмет виявлення академічного плагіату програмами “Etxt Антиплагиат”, “AntiPlagiarism.NET” та “AdvegoPlagiatus 1.3.1.7”. За період з 01.09.2015 до 01.09.2016 р. проведено перевірку 429 наукових праць: 208 статей у фахові наукові журнали; 99 тез доповідей; 66 дисертаційних робіт та авторефератів; 14 наукових звітів; 22 методичних рекомендацій та методичних вказівок; 11 підручників та навчальних посібників, 9 монографій. Система запобігання та виявлення академічного плагіату розповсюджується на наукові та навчальні праці науково-педа­гогічних, наукових та інших працівників університету, докто­рантів, аспірантів; осіб, прикріплених до університету з метою здобуття наукового ступеня доктора філософії (кандидата наук) поза аспірантурою, та студентів. Виявлення в поданій до захисту дисертації (науковій доповіді) академічного плагіату є підставою для відмови у присудженні відповідного наукового ступеня.
РОЛЬ МАТЕРІАЛЬНО-ТЕХНІЧНОЇ БАЗИ ТА НАУКОВО-ПЕДАГОГІЧНОГО ЗАБЕЗПЕЧЕННЯ В ПІДГОТОВЦІ ЛІКАРЯ МАЙБУТНЬОГО (СІМЕЙНОГО ЛІКАРЯ)
Authors: Shyshka I. V. , Kudiyevskyi A. V.
Published: November 2016

Мета роботи – обґрунтувати роль та значення матеріально-технічної бази та науково-педагогічного забезпечення в підготовці лікаря майбутнього. Взаємопорозуміння керівників вищих навчальних закладів (Академії післядипломної підготовки лікарів та Медичного університету) з адміністрацією баз практики, охорони здоров’я в залученні сучасних методів дослідження та апаратури для всебічної підготовки лікаря майбутнього.У статті представлено світогляд випускників вузу, інтернів та клінічних ординаторів на систему підготовки сімейного лікаря в цілому на перспективу сімейної медицини.