bluuebunny/crossref_metadata_2025 huggingface dataset:
Standard wound management versus negative-pressure wound therapy in the treatment of adult patients having surgical incisions for major trauma to the lower limb—a two-arm parallel group superiority randomised controlled trial: protocol for Wound Healing in Surgery for Trauma (WHIST)
Authors: Achten Juul , Vadher Karan , Bruce Julie , Nanchahal Jagdeep , Spoors Louise , Masters James P , Dutton Susan , Madan Jason , Costa Matthew L
Published: June 2018

Introduction

Patients with closed high-energy injuries associated with major trauma have surprisingly high rates of surgical site infection in incisions created during fracture fixation. One factor that may reduce the risk of surgical site infection is the type of dressing applied over the closed surgical incision. In this multicentre randomised clinical trial, negative-pressure wound therapy will be compared with standard dressings with outcomes of deep infection, quality of life, pain and disability.

Methods and analysis

Adult patients presenting to hospital within 72 hours of sustaining major trauma, requiring a surgical incision to treat a fractured lower limb, are eligible for inclusion. Randomisation, stratified by trial centre, open/closed fracture at presentation and Injury Severity Score (ISS) ≤15 versus ISS ≥16 will be administered via a secure web-based service using minimisation. The random allocation will be to either standard wound management or negative-pressure wound therapy.

Trial participants will usually have clinical follow-up at the local fracture clinic for a minimum of 6 months, as per standard National Health Service practice. Diagnosis of deep infection will be recorded at 30 days. Functional, pain and quality of life outcome data will be collected using the Disability Rating Index, Douleur Neuropathique Questionnaire and Euroqol - 5 Dimension - 5 level (EQ-5D-5L) questionnaires at 3 months and 6 months postinjury. Further data will be captured on resource use and any late postoperative complications.

Longer term outcomes will be assessed annually for 5 years and reported separately.

Ethics and dissemination

National Research Ethics Committee approved this study on 16 February 2016 16/WM/0006.

The National Institute for Health Research Health Technology Assessment monograph and a manuscript to a peer-reviewed journal will be submitted on completion of this trial. The results of this trial will inform clinical practice on the clinical and cost-effectiveness of the treatment of this injury.

Trial registration number

ISRCTN12702354; Pre-results.
Dissemination of evidence in paediatric emergency medicine: a quantitative descriptive evaluation of a 16-week social media promotion
Authors: Gates Allison , Featherstone Robin , Shave Kassi , Scott Shannon D , Hartling Lisa
Published: June 2018

Objectives

TRanslating Emergency Knowledge for Kids (TREKK) and Cochrane Child Health collaborate to develop knowledge products on paediatric emergency medicine topics. Via a targeted social media promotion, we aimed to increase user interaction with the TREKK and Cochrane Child Health Twitter accounts and the uptake of TREKK Bottom Line Recommendations (BLRs) and Cochrane systematic reviews (SRs).

Design

Quantitative descriptive evaluation.

Setting

We undertook this study and collected data via the internet.

Participants

Our target users included online healthcare providers and health consumers.

Intervention

For 16 weeks, we used Twitter accounts (@TREKKca and @Cochrane_Child) and the Cochrane Child Health blog to promote 6 TREKK BLRs and 16 related Cochrane SRs. We published 1 blog post and 98 image-based tweets per week.

Primary and secondary outcome measures

The primary outcome was user interaction with @TREKKca and @Cochrane_Child. Secondary outcomes were visits to TREKK’s website and the Cochrane Child Health blog, clicks to and views of the TREKK BLRs, and Altmetric scores and downloads of Cochrane SRs.

Results

Followers to @TREKKca and @Cochrane_Child increased by 24% and 15%, respectively. Monthly users of TREKK’s website increased by 29%. Clicks to the TREKK BLRs increased by 22%. The BLRs accrued 59% more views compared with the baseline period. The 16 blog posts accrued 28% more views compared with the 8 previous months when no new posts were published. The Altmetric scores for the Cochrane SRs increased by ≥10 points each. The mean number of full text downloads for the promotion period was higher for nine and lower for seven SRs compared with the 16-week average for the previous year (mean difference (SD), +4.0 (22.0%)).

Conclusions

There was increased traffic to TREKK knowledge products and Cochrane SRs during the social media promotion. Quantitative evidence supports blogging and tweeting as dissemination strategies for evidence-based knowledge products.
The clinician impact and financial cost to the NHS of litigation over pregabalin: a cohort study in English primary care
Authors: Croker Richard , Smyth Darren , Walker Alex J , Goldacre Ben
Published: June 2018

Objectives

Following litigation over pregabalin’s second-use medical patent for neuropathic pain, National Health Service (NHS) England was required by the court to instruct general practitioners (GPs) to prescribe the branded form (Lyrica) for pain. Pfizer’s patent was found invalid in 2015, a ruling subject to ongoing appeals. If the Supreme Court appeal in February 2018, whose judgement is awaited, is unsuccessful, the NHS can seek to reclaim excess prescribing costs. We set out to describe the variation in prescribing of pregabalin as branded Lyrica, geographically and over time; to determine how clinicians responded to the NHS England instruction to GPs; and to model excess costs to the NHS attributable to the legal judgements.

Setting

English primary care.

Participants

English general practices.

Primary and secondary outcome measures

Variation in prescribing of branded Lyrica across the country before and after the NHS England instruction, by practice and by Clinical Commissioning Group; excess prescribing costs.

Results

The proportion of pregabalin prescribed as Lyrica increased from 0.3% over 6 months before the NHS England instruction (September 2014 to February 2015) to 25.7% afterwards (April to September 2015). Although 70% of pregabalin is estimated to be for pain, including neuropathic pain, only 11.6% of practices prescribed Lyrica at this level; the median proportion prescribed as Lyrica was 8.8% (IQR 1.1%–41.9%). If pregabalin had come entirely off patent in September 2015, and Pfizer had not appealed, we estimate the NHS would have spent £502 million less on pregabalin to July 2017.

Conclusion

NHS England instructions to GPs regarding branded prescription of pregabalin were widely ignored and have created much debate around clinical independence in prescribing. Protecting revenue from ‘skinny labels’ will pose a challenge. If Pfizer’s final appeal on the patent is unsuccessful, the NHS can seek reimbursement of excess pregabalin prescribing costs, potentially £502 million.
Evaluation of the clinical and cost-effectiveness of the York Faecal Calprotectin Care Pathway
Authors: Turvill James , Turnock Daniel , Holmes Hayden , Jones Alison , Mclaughlan Eleanor , Hilton Victoria , Marriott Stacey
Published: June 2018

Objective

To evaluate the sensitivity and specificity of the York Faecal Calprotectin Care Pathway (YFCCP) and undertake a health economics analysis. The YFCCP has been introduced in support of the National Institute for Health and Care Excellence (NICE) guidance DG11. It is designed to improve the sensitivity and specificity of faecal calprotectin (FC) in discriminating the irritable bowel syndrome from inflammatory bowel disease in primary care.

Design

To prospectively evaluate the clinical outcomes at 6 months of the first 1005 patients entering the YFCCP. To develop a cost-consequence model using two comparators: one based on clinical assessment and the C reactive protein/erythrocyte sedimentation rate without using FC, and the second using single testing of the standard FC cut-off.

Setting

North Yorkshire primary care practices.

Patients

Primary care patients fulfilling NICE DG11.

Interventions

The YFCCP.

Main outcome measures

Clinical outcome measures from secondary care records.

Results

The sensitivity and specificity of the YFCCP are 0.94 (0.85 to 0.98) and 0.92 (0.90 to 0.94), giving a negative and positive predictive value of 0.99 (0.98 to 1.0) and 0.51 (0.43 to 0.59), respectively.

Conclusions

The YFCCP overcomes the challenges experienced with FC use in primary care, its efficacy matching initial NICE projections. It is readily incorporated into clinical practice. It should represent the framework on which to increase NICE DG11 implementation nationally.
Clinic, courtroom or (specialist) committee: in the best interests of the critically Ill child?
Authors: Huxtable Richard
Published: June 2018

Law’s processes are likely always to be needed when particularly intractable conflicts arise in relation to the care of a critically ill child like Charlie Gard. Recourse to law has its merits, but it also imposes costs, and the courts’ decisions about the best interests of such children appear to suffer from uncertainty, unpredictability and insufficiency. The insufficiency arises from the courts’ apparent reluctance to enter into the ethical dimensions of such cases. Presuming that such reflection is warranted, this article explores alternatives to the courts, and in particular the merits of specialist ethics support services, which appear to be on the rise in the UK. Such specialist services show promise, as they are less formal and adversarial than the courts and they appear capable of offering expert ethical advice. However, further research is needed into such services – and into generalist ethics support services – in order to gauge whether this is indeed a promising development.
Shifting understandings of labour pain in Canadian medical history
Authors: Wood Whitney
Published: June 2018

While pain in childbirth is a universal, cross-cultural, biological reality, individual experiences and perceptions of this pain are historically and culturally specific. At the turn of the 20th century—a key period in terms of both the medicalisation of birth and the professionalisation of obstetrics in the Canadian context—Canadian physicians understood and conceptualised ‘birth pangs’ in a number of varying (and at times competing) ways. Throughout the 19th century, doctors emphasised the broader utility of pain as a diagnostic tool and a physiologically necessary part of the birthing process. With the advent of anaesthetics, including chloroform and ether, however, a growing subset of the medical profession simultaneously lauded the professional, physiological, and humanitarian benefits of pain relief. By the first decades of the 20th century, shifting understandings of labour pain—and particularly growing distinctions between ‘pain’ and ‘contraction’ in mainstream medical discourses—underscored the increasing use of obstetric anaesthesia. Drawing on a broad range of medical texts and professional literature, and focusing on a key historical moment when the introduction and adoption of a new medical technology opened up possibilities for professional debate, this paper unpacks both the micropolitics and the macropolitics of shifting understandings of labour pain in modern Canadian medical history.
Prevalence of degenerative changes and overlap with spondyloarthritis-associated lesions in the spine of patients from the DESIR cohort
Authors: de Bruin Freek , Treyvaud Marco O , Feydy Antoine , de Hooge Manouk , Pialat Jean-Baptiste , Dougados Maxime , Gossec Laure , Bloem Johan L , van der Heijde Désirée , Reijnierse Monique
Published: June 2018

Objectives

To describe the prevalence of degenerative changes on MRI and conventional radiographs of the spine in a young population with suspicion of axial spondyloarthritis (axSpA) and assess whether it is possible to discriminate between degenerative changes and lesions associated with axSpA.

Methods

Whole spine MRI and cervical and lumbar radiographs of patients ≥18 years with chronic back pain (≥3 months, ≤3 years, onset <50 years) were assessed for degeneration by two readers, and for SpA lesions by two other readers, all blinded for clinical information and results of the other readers. Degenerative scores were adjudicated in case of disagreement (by a third reader). Patients fulfilling and not fulfilling the Assessment of SpondyloArthritis international Society axSpA criteria were compared for prevalence of degenerative lesions. Scores for degenerative and SpA lesions were compared, and overlap was defined as the presence of both types of lesions in a single vertebral unit (VU).

Results

In 456/648 (70.4%) patients (46.8% men, mean age 33.6), degenerative lesions were found with similar percentages in patients with no axSpA and with axSpA (72.4% and 69.2%, p=0.45). Modic changes were found more often in patients with no axSpA (29/239, 12.1%) versus patients with axSpA (19/409, 4.6%, p=0.01). Other lesions were evenly distributed. Overlap was minimal in 19 patients (3.0%) and 32/14 674 (0.2%) VUs for SpA reader 1 and in 23 patients (3.6%) and 34/14 674 VUs (0.2%) for SpA reader 2.

Conclusion

The prevalence of degeneration is high in an early inflammatory back pain cohort. Discrimination between degeneration and axSpA lesions is very well possible with little overlap between degenerative and axSpA readings.
Restrictive lung defects: parenchymal, chest wall and neuromuscular
Authors: Shanks Anne-Marie , Desai Sujal R , Rice Alexandra , Thomas Stephen R , Polkey Michael I , George Peter M
Published: June 2018

Sarcoidosis is a multisystem condition which may affect a number of organs and, within the cardiopulmonary system, most commonly manifests as parenchymal, airway-centred, nodal, vascular or cardiac disease. Pleural involvement is rare, but well described, and often presents as pleural effusions or pleural thickening. Here, we present the first case of active sarcoidosis manifesting as bilateral pleural calcification. We highlight the importance of a nuanced understanding of pulmonary physiology when dissecting coexistent extrathoracic and intrathoracic pulmonary restriction. We demonstrate the value of positron emission tomography scanning for identification of sites of sarcoid activity, in this case the pleura, to ensure tissue confirmation of this rare but functionally important manifestation of disease. Sarcoidosis should be considered within the differential diagnosis for patients with pleural calcification, not explained by more common causes.
Impact of the WHO FCTC over the first decade: a global evidence review prepared for the Impact Assessment Expert Group
Authors: Chung-Hall Janet , Craig Lorraine , Gravely Shannon , Sansone Natalie , Fong Geoffrey T
Published: June 2018

Objective

To present findings of a narrative review on the implementation and effectiveness of 17 Articles of the WHO Framework Convention on Tobacco Control (FCTC) during the Treaty’s first decade.

Data sources

Published reports on global FCTC implementation; searches of four databases through June 2016; hand-search of publications/online resources; tobacco control experts.

Study selection

WHO Convention Secretariat global progress reports (2010, 2012, 2014); 2015 WHO report on the global tobacco epidemic; studies of social, behavioural, health, economic and/or environmental impacts of FCTC policies.

Data extraction

Progress in the implementation of 17 FCTC Articles was categorised (higher/intermediate/lower) by consensus. 128 studies were independently selected by multiple authors in consultation with experts.

Data synthesis

Implementation was highest for smoke-free laws, health warnings and education campaigns, youth access laws, and reporting/information exchange, and lowest for measures to counter industry interference, regulate tobacco product contents, promote alternative livelihoods and protect health/environment. Price/tax increases, comprehensive smoking and marketing bans, health warnings, and cessation treatment are associated with decreased tobacco consumption/health risks and increased quitting. Mass media campaigns and youth access laws prevent smoking initiation, decrease prevalence and promote cessation. There were few studies on the effectiveness of policies in several domains, including measures to prevent industry interference and regulate tobacco product contents.

Conclusions

The FCTC has increased the implementation of measures across several policy domains, and these implementations have resulted in measurable impacts on tobacco consumption, prevalence and other outcomes. However, FCTC implementation must be accelerated, and Parties need to meet all their Treaty obligations and consider measures that exceed minimum requirements.
Peroxisome proliferator-activated receptor gamma coactivator 1α variation: a closer look at obesity onset age and its related metabolic status and body composition
Authors: Zamaninour Negar , Mirzaei Khadijeh , Maghbooli Zhila , Keshavarz Seyed Ali
Published: June 2018

There is a lack of knowledge regarding the effect of polymorphisms of the peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) gene on the age of obesity onset. Hence, 3 polymorphisms of the PGC-1α gene (PGC-1α rs17574213, rs8192678, and rs3755863) were examined in association with obesity onset age. Also, obesity onset age-related metabolic status and body composition were evaluated. This cross-sectional study was conducted with a total of 321 obese participants. Anthropometric and biochemical information, body composition, and PGC-1α gene sequences were analyzed. The rs17574213 polymorphism was associated with obesity onset in children aged <1 years and 10–18 years. The rs8192678 polymorphism was associated with obesity onset in adulthood. Body mass index, body fat percent, and trunk fat were higher in groups whose obesity began at age <1 year or 10–18 years than in other groups. Serum levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total cholesterol were lowest in the group with obesity onset between the ages of 10 and 18 years. Visceral fat and fasting blood glucose were highest in those whose obesity began in adulthood. In conclusion, 2 polymorphisms of the PGC-1α gene were associated with obesity onset age.
Sensitivity analysis and optimization of EDM process parameters
Authors: Ragavendran Uvaraja , Ghadai Ranjan Kumar , Bhoi Akash Kumar , Ramachandran Manickam , Kalita Kanak
Published: June 2018

Electrical discharge machining (EDM) is a broadly used nonconventional material removal process for the machining of conductive work material irrespective of their hardness. In this article, empirical models for material removal rate (MRR) and surface roughness (Ra) of the workpiece are developed based on the extensive experiments performed on a special steel (WP7V) workpiece using a copper electrode. To account for the various parameters, an experimental design based on response surface methodology (RSM) is conducted considering three different factors namely — current, pulse-on-time, and pulse-off-time, each having three different levels. Analysis of variance (ANOVA) is conducted to test the statistical significance of the proposed empirical models. It is essential to determine the relationship and significance of input–output variation. Thus a sensitivity analysis is conducted. The interaction effect of input variables is also studied. Two different state-of-art optimization techniques, namely genetic algorithm (GA) and particle swarm optimization (PSO), are applied to predict the optimal combination of process parameters. Finally, multi-objective optimization is also carried out to simultaneously maximize MRR while minimizing Ra.
An analog of magnetic oscillations for neutral atoms with induced electric dipole
Authors: Farias B. , Furtado C.
Published: June 2018

We show that the analog of de Haas–van Alphen effect (adHvA) can be generated in a two-dimensional (2D) atomic gas by the interaction between an induced electric dipole and an electromagnetic field. When the neutral atoms move in a properly designed field configuration, we have a quantization similar to the Landau levels. The effective magnetic field dependence of the oscillation amplitude of the the energy and the analog magnetization of the atomic cloud are studied. We also estimate the area of the Fermi circle of the atomic gas.
OUTSOURCING NEW PRODUCT DEVELOPMENT FOSTERED BY DISRUPTIVE TECHNOLOGICAL INNOVATION: A DECISION-MAKING MODEL
Authors: CANTONE LUIGI , TESTA PIERPAOLO , HOLLENSEN SVEND , CANTONE GIUSEPPE FABIO
Published: June 2018

Several studies in the literature have addressed the issue of outsourcing in relation to New Product Development (NPD) or R&D processes. However, the issue of how the outsourcing decisions in the NPD process are best undertaken by the firms has not been fully addressed. Understanding factors influencing the decision of innovation outsourcing more likely remains a need within the current research stream. As it stands, the existing literature takes account of neither a complete set of decision making dimensions, nor the specificity of the NPD process, especially when a disruptive technology fosters product innovation. Although these studies have analysed the antecedents of the innovation outsourcing, the decision-making dimensions are not considered in an integrated multidimensional decision-making model, that considers the inter-related effects of their contemporaneous consideration. There are, therefore, significant gaps in the literature, which this article intends to fill. Our study aims to understand how organisations approach outsourcing decisions relating to NPD activities in technology intensive industries, and the performance implications of these decisions. The context of the study is that of aircraft industry. Therefore, this article discusses the findings of an empirical research that explores an embedded and in-depth longitudinal case study, namely, the Boeing 787-8 programme (the first model of the B787 Dreamliner programme). This new aircraft is a disruptive technology product innovation within the industry because it adopts new material technologies that make it possible to meet future customer needs. The programme has radically changed the partnership model adopted in the industry’s supply chain. The aim of the empirical research is to verify how the proposed model works to investigate outsourcing strategies related to the Boeing 787 Dreamliner programme. The research question that we aim to answer is: which strategic dimensions in a decision-making model are able to extensively and thoroughly address the outsourcing decisions relating to NPD activities given the hypothesis that a disruptive technology fosters product innovation?
Duality and Charged Pion Condensation in Chirally Asymmetric Dense Quark Matter in the Framework of an NJL2 Model
Authors: Khunjua T. G. , Zhukovsky V. C. , Klimenko K. G. , Zhokhov R. N.
Published: June 2018

In this talk we present investigation of the phase structure of a (1+1)-dimensional quark model with four-quark interaction and in the presence of baryon ([Formula: see text]), isospin ([Formula: see text]) and chiral isospin ([Formula: see text]) chemical potentials. Spatially homogeneous and inhomogeneous (chiral density wave (for chiral condensate) and single wave (for charged pion condensate)) condensates are considered. It is established that in the large-[Formula: see text] limit ([Formula: see text] is the number of colored quarks) there exists a duality correspondence between the chiral symmetry breaking phase and the charged pion condensation (PC) one. The primary conclusion of this investigation is the fact that chiral isospin chemical potential generates charged pion condensation with non-zero baryon density in dense quark matter. Moreover, it is shown that inhomogeneous charged PC phase with nonzero baryon density is induced in the model by arbitrary small values of the chemical potential [Formula: see text] (for a rather large region of [Formula: see text] and [Formula: see text]).
Different Ways to Estimate Graviton Mass
Authors: Zakharov Alexander F. , Jovanović Predrag , Borka Dusko , Jovanović Vesna Borka
Published: June 2018

An experimental detection of graviton is extremely hard problem, however, there are different ways to evaluate a graviton mass if it is non-vanishing. Theories of massive gravity or theories with non-vanishing graviton mass initially have a number of pathologies such as discontinuities, ghosts etc. In last years theorists found ways to overcome weaknesses of such theories meanwhile observational features are also discussed. In the first publication reporting about the discovery of gravitational waves from the binary black hole system the LIGO-Virgo collaboration obtained the graviton mass constraint around [Formula: see text] eV (later the estimate was improved with new data). A comparable and consistent graviton mass constraint around [Formula: see text] eV has been obtained from analysis of the bright star S2 trajectory near the Galactic Center.
Is There a Hollow Inside the Proton?
Authors: Petrov V. A. , Samokhin A. P.
Published: June 2018

We discuss a recently proposed interpretation of some model descriptions of the proton-proton elastic scattering data as a manifestation of alleged relative transparency of the central part of the interaction region in the impact parameter space. We argue that the presence of nonzero real part of the elastic scattering amplitude in the unitarity condition enables to conserve the traditional interpretation.
The Effects of Majorana Phases in Estimating the Masses of Neutrinos
Authors: Francis Ng. K. , Nath Ankur
Published: June 2018

Majorana CP violating phases coming from heavy right-handed Majorana mass matrices([Formula: see text]) are considered to estimate the masses of neutrinos. The effects of phases on quasi-degenerate neutrinos mass matrix obeying [Formula: see text] symmetry predicts the results consistent with observations for (i) solar mixing angle([Formula: see text]) below TBM, (ii) absolute neutrino mass parameters[[Formula: see text]] in neutrinoless double beta([Formula: see text]) decay, and (iii) cosmological upper bound [Formula: see text]. Analysis is carried out through parameterization of light left-handed Majorana neutrino matrices ([Formula: see text]) using only two unknown parameters ([Formula: see text]) within [Formula: see text] symmetry. We consider the charge lepton and up quark matrices as diagonal form of Dirac neutrino mass matrix ([Formula: see text]), and [Formula: see text] are generated using [Formula: see text] through inversion of Type-I seesaw formula. The analysis shows that the masses of neutrinos are in agreement with the upper bound from cosmology and neutrinoless double beta decay. The results presented in this article will have important implications in discriminating the neutrinos mass models.
Where is PELE?
Authors: John Luis Henrik , Sarkar Chayan , Prasad R. Venkatesha
Published: June 2018

Smartphones or in general handhelds commonly used for indoor localization purposes are not a viable option in places where people do not carry them all the time - for example, home and office. Alternatively, wearable devices can partially solve this problem but have many limitations with respect to power supply, processing capability, and availability of sensors. These issues prevent the adoption of many common handheld localization solutions. In this work, we present
PE
rvasive
L
ocalization
E
ngine (PELE), a distributed localization system that uses wearable and handheld jointly to address the above drawbacks. Using only magnetometer, accelerometer, and Bluetooth radio, localization is performed by means of a particle filter. In addition, a dynamic handoff mechanism is presented, which uses the wearable only when it is necessary, thus reducing energy consumption on the wearable without affecting the desired localization accuracy. Evaluating the system with ten participants, we achieve a localization accuracy of 90.31 % in an indoor environment spanning about 320 m
2
.
Automation of feature engineering for IoT analytics
Authors: Banerjee Snehasis , Chattopadhyay Tanushyam , Pal Arpan , Garain Utpal
Published: June 2018

This paper presents an approach for automation of interpretable feature selection for Internet Of Things Analytics (IoTA) using machine learning (ML) techniques. Authors have conducted a survey over different people involved in different IoTA based application development tasks. The survey reveals that feature selection is the most time consuming and niche skill demanding part of the entire workflow. This paper shows how feature selection is successfully automated without sacrificing the decision making accuracy and thereby reducing the project completion time and cost of hiring expensive resources. Several pattern recognition principles and state of art (SoA) ML techniques are followed to design the overall approach for the proposed automation. Three data sets are considered to establish the proof-of-concept. Experimental results show that the proposed automation is able to reduce the time for feature selection to 2 days instead of 4 -- 6 months which would have been required in absence of the automation. This reduction in time is achieved without any sacrifice in the accuracy of the decision making process. Proposed method is also compared against Multi Layer Perceptron (MLP) model as most of the state of the art works on IoTA uses MLP based Deep Learning. Moreover the feature selection method is compared against SoA feature reduction technique namely Principal Component Analysis (PCA) and its variants. The results obtained show that the proposed method is effective.
Continuous Manufacturing in Pharmaceutical Process Development and Manufacturing
Authors: Burcham Christopher L. , Florence Alastair J. , Johnson Martin D.
Published: June 2018

The pharmaceutical industry has found new applications for the use of continuous processing for the manufacture of new therapies currently in development. The transformation has been encouraged by regulatory bodies as well as driven by cost reduction, decreased development cycles, access to new chemistries not practical in batch, improved safety, flexible manufacturing platforms, and improved product quality assurance. The transformation from batch to continuous manufacturing processing is the focus of this review. The review is limited to small, chemically synthesized organic molecules and encompasses the manufacture of both active pharmaceutical ingredients (APIs) and the subsequent drug product. Continuous drug product is currently used in approved processes. A few examples of production of APIs under current good manufacturing practice conditions using continuous processing steps have been published in the past five years, but they are lagging behind continuous drug product with respect to regulatory filings.
The Early Outcomes of Nurse Case Management in Patients with Acute Ischemic Stroke Treated with Intravenous Recombinant Tissue Plasminogen Activator: A Prospective Randomized Controlled Trial
Authors: Kummarg Urai , Sindhu Siriorn , Muengtaweepongsa Sombat
Published: June 2018

Background. Intravenous recombinant tissue plasminogen activator (i.v. rt-PA) is the milestone treatment for patients with acute ischemic stroke. Stroke Fast Track (SFT) facilitates time reduction, guarantees safety, and promotes good clinical outcomes in i.v. rt-PA treatment. Nursing case management is a healthcare service providing clinical benefits in many specific diseases. The knowledge about the efficacy of a nurse case management for Stroke Fast Track is limited. We aim to study the effect of nurse case management on clinical outcomes in patients with acute ischemic stroke involving intravenous recombinant tissue plasminogen activator (i.v. rt-PA) treatment. Methods. Seventy-six patients with acute ischemic stroke who received i.v. rt-PA treatment under Stroke Fast Track protocol of Thammasat University Hospital were randomized into two groups. One group was assigned to get standard care (control) while another group was assigned to get standard care under a nurse case management. The National Institute of Health Stroke Scale (NIHSS) at 24 hours after treatment between the control and the experimental groups was evaluated. Results. Time from triage to treatment in the experimental group was significantly faster than in the control group (mean = 39.02 and 59.37 minutes, respectively; p=.001). The NIHSS at 24 hours after treatment in the nurse case management group was significantly improved as compared to the control group (p=.001). No symptomatic intracranial hemorrhage (sICH) was detected at 24 hours after onset in both groups. Conclusion. The nurse case management should provide some benefits in the acute stroke system. Although the early benefit is demonstrated in our study, further studies are needed to ensure the long-term benefit and confirm its profit in patients with acute ischemic stroke.
Statistics of Finite Scale Local Lyapunov Exponents in Fully Developed Homogeneous Isotropic Turbulence
Authors: de Divitiis Nicola
Published: June 2018

The present work analyzes the statistics of finite scale local Lyapunov exponents of pairs of fluid particles trajectories in fully developed incompressible homogeneous isotropic turbulence. According to the hypothesis of fully developed chaos, this statistics is here analyzed assuming that the entropy associated with the fluid kinematic state is maximum. The distribution of the local Lyapunov exponents results in an unsymmetrical uniform function in a proper interval of variation. From this PDF, we determine the relationship between average and maximum Lyapunov exponents and the longitudinal velocity correlation function. This link, which in turn leads to the closure of von Kármán–Howarth and Corrsin equations, agrees with results of previous works, supporting the proposed PDF calculation, at least for the purposes of the energy cascade main effect estimation. Furthermore, through the property that the Lyapunov vectors tend to align the direction of the maximum growth rate of trajectories distance, we obtain the link between maximum and average Lyapunov exponents in line with the previous results. To validate the proposed theoretical results, we present different numerical simulations whose results justify the hypotheses of the present analysis.
Air Traffic Efficiency Analysis of Airliner Scheduled Flights Using Collaborative Actions for Renovation of Air Traffic Systems Open Data
Authors: Harada Akinori , Ezaki Tooru , Wakayama Tomoaki , Oka Koichi
Published: June 2018

The increase in air traffic worldwide requires improvement of flight operational efficiency. This study aims to reveal the potential benefits, namely, savings on fuel consumption and flight time, which are expected for Japanese airspace, by statistically evaluating the operational efficiency defined by average differences of fuel consumption, flight time, and flight distance between the original and the optimized flight of domestic flights in Japan. The aircraft position and time data used in this study were obtained from Collaborative Actions for Renovation of Air Traffic Systems Open Data—the radar data released by the Japan Civil Aviation Bureau. Flight information, such as air data and fuel flow, is estimated by applying meteorological data and aircraft performance model to the position information of radar data. Each reconstructed trajectory is optimized in terms of flight fuel consumption and flight time with an assumed cost index (CI). Dynamic programming is used as the trajectory optimization method. The flight fuel consumption and flight time of the optimized flight are compared with the original values to evaluate the operational efficiency. Herein, approximately one-third of 1-day data, i.e., 1087 cases of four aircraft types, are analyzed with reasonable CI settings. Our research findings suggest that flight fuel consumption and flight distance can be saved by 312 kg and 19.7 km, respectively, on average for the object flights. Following a statistical comparison between the original and the optimized flights, it was observed that two types of features, namely, flying on a detoured path and flying with nonoptimal altitude and speed in the cruise phase, are major factors which deteriorate the total operational efficiency in terms of fuel consumption, flight time, and flight distance.
Implementation of Biological Control to the Integrated Control of Strongyle Infection among Wild Captive Equids in a Zoological Park
Authors: Palomero A. M. , Hernández J. A. , Cazapal-Monteiro C. F. , Balán Fabián Arroyo , Silva M. I. , Paz-Silva Adolfo , Sánchez-Andrade R. , Vázquez María Sol Arias
Published: June 2018

The integrated control of strongyles was assayed for a period of three years in wild equids (zebras, European donkeys, and African wild asses) captive in a zoo and infected by strongyles. During three years control of parasites consisted of deworming with ivermectin + praziquantel; equids also received every two days commercial nutritional pellets containing a blend of 104 - 105 spores of the fungi Mucor circinelloides + Duddingtonia flagrans per kg meal. Coprological analyses were done monthly to establish the counts of eggs of strongyles per gram of feces (EPG). The reductions in the fecal egg counts (FECR) and in the positive horses (PHR) were calculated fifteen days after deworming; the egg reappearance period (ERP) and the time elapsed from the previous deworming (TPD) were also recorded. Four anthelmintic treatments were administered during the assay, three times throughout the first 2 yrs, and another treatment during the last one. FECR values of 96-100% and 75-100% for the PHR were recorded. The ERP oscillated between eight and twenty-eight weeks, and the TPD ranged from four to eighteen months, increasing to the end of the trial. No side effects were observed in any of the equids. It is concluded that integrated control of strongyles among equids captive in a zoo can be developed by anthelmintic deworming together with the administration of pellets manufactured with spores of parasiticide fungi every two days.
Multi-Fiber-Reinforced Composites for the Coronoradicular Reconstruction of Premolar Teeth: A Finite Element Analysis
Authors: Richert Raphaël , Robinson Philip , Viguie Gilbert , Farges Jean-Christophe , Ducret Maxime
Published: June 2018

A coronoradicular reconstruction (CRR) has conventionally used a metallic inlay core (MIC) or a single-fiber-reinforced composite (sFRC) but extensive dentin removal can lead to root fracture. We propose herein a multi-fiber-reinforced composite (mFRC) based on a bundle of thin flexible fibers that can be adapted to the root anatomy without removing additional dentin. The aim of this study was to compare the mechanical behavior of the root reconstructed with mFRC, MIC, or sFRC using a finite element analysis (FEA). Models with or without a ferrule effect were created using Autodesk© software and divided into four parts: root, post, bonding composite or cement, and zirconia crown. For both models, extreme stress values (ESV), stress distribution, and risk of fracture were calculated for an oblique force (45°) of 100 N applied to the top of the buccal cusp. Results indicated that mFRC and mFRCG present a lower risk of fracture of the root and of the CRR without ferrule and thus could be valuable alternatives for premolar CRR. Further studies are necessary to evaluate the clinical success of these CRR.
The Inverse Problem of Identification of Hydrogen Permeability Model
Authors: Zaika Yury V. , Rodchenkova Natalia I. , Kostikova Ekaterina K.
Published: June 2018

One of the technological challenges for hydrogen materials science is the currently active search for structural materials with important applications (including the ITER project and gas-separation plants). One had to estimate the parameters of diffusion and sorption to numerically model the different scenarios and experimental conditions of the material usage (including extreme ones). The article presents boundary value problems of hydrogen permeability and thermal desorption with dynamical boundary conditions. A numerical method is developed for TDS spectrum simulation, where only integration of a nonlinear system of low order ordinary differential equations is required. The main final output of the article is a noise-resistant algorithm for solving the inverse problem of parametric identification for the aggregated experiment where desorption and diffusion are dynamically interrelated (without the artificial division of studies into the diffusion limited regime (DLR) and the surface limited regime (SLR)).
TFF1andTFF3mRNAs Are Higher in Blood from Breast Cancer Patients with Metastatic Disease than Those without
Authors: Elnagdy Marwa H. , Farouk Omar , Seleem Amal K. , Nada Hoda A.
Published: June 2018

Introduction. Breast cancer metastasis occurs when tumor cells dissociate from the primary tumor and migrate to distant organs through the peripheral bloodstream or lymphatic drainage. Circulating tumor cells (CTCs) originate from primary sites or metastases and circulate in the patients’ bloodstream. Molecular assays for the detection and molecular characterization of CTCs can serve as a liquid biopsy and can represent an alternative to invasive biopsies as a source of tumor tissue in the metastatic patients.Patients and Methods. We analyzed the presence of CTCs in the peripheral blood of 50 breast cancer patients by quantitative real-time reverse transcriptase polymerase chain reaction (RT-qPCR) to detecttrefoil factor family(TFF)1and3genes.Results. We found significant difference in the level of bothTFF1andTFF3mRNA in the blood of nonmetastatic versus metastatic breast cancer patients (p=0.001 and p= 0.038, respectively).TFF1mRNA was detected at higher levels in 34.6% of metastatic breast cancer patients as compared to 0% of nonmetastatic (p= 0.002). As regardsTFF3mRNA, it was detected at higher levels in 46.2% of metastatic breast cancer patients as compared to 4% of nonmetastatic (p= 0.026). Moreover, we found that the high level of bothTFF1andTFF3mRNA was related to estrogen status of the patients. The detection of high level ofTFF1mRNA in CTCs was associated with bone metastases (77.8%), while that ofTFF3was related to lymph node involvement (75%) and lung metastases (68.8%).Conclusion. The combined measurement of bothTFF1andTFF3mRNA level for differentiation of metastatic from nonmetastatic breast cancer gave 57.69% sensitivity and 83.3% specificity.
TRIF Regulates BIC/miR-155 via the ERK Signaling Pathway to Control the ox-LDL-Induced Macrophage Inflammatory Response
Authors: Wu Yaxi , Ye Jinshan , Guo Ruiwei , Liang Xing , Yang Lixia
Published: June 2018

Toll/IL-1R-domain-containing adaptor-inducing IFN-β (TRIF) is an important adaptor for TLR3- and TLR4-mediated inflammatory signaling pathways. Recent studies have shown that TRIF plays a key role in vessel inflammation and atherosclerosis; however, the precise mechanisms are unclear. We investigated the mechanisms of the TRIF-regulated inflammatory response in RAW264.7 macrophages under oxidized low-density lipoprotein (ox-LDL) stimulation. Our data show that ox-LDL induces TRIF, miR-155, and BIC expression, activates the ERK1/2 and SOCS1-STAT3-NF-κB signaling pathways, and elevates the levels of IL-6 and TNF-α in RAW264.7 cells. Knockdown of TRIF using TRIF siRNA suppressed BIC, miR-155, IL-6, and TNF-α expression and inhibited the ERK1/2 and SOCS1-STAT3-NF-κB signaling pathways. Inhibition of ERK1/2 signaling also suppressed BIC and miR-155 expression. These findings suggest that TRIF plays an important role in regulating the ox-LDL-induced macrophage inflammatory response and that TRIF modulates the expression of BIC/miR-155 and the downstream SOCS1-STAT3-NF-κB signaling pathway via ERK1/2. Therefore, TRIF might be a novel therapeutic target for atherosclerosis.
Geminin Orchestrates Somite Formation by Regulating Fgf8 and Notch Signaling
Authors: Huang Wei , Zhang Yu , Cao Kang , Luo Lingfei , Huang Sizhou
Published: June 2018

During somitogenesis, Fgf8 maintains the predifferentiation stage of presomitic mesoderm (PSM) cells and its retraction gives a cue for somite formation. Delta/Notch initiates the expression of oscillation genes in the tail bud and subsequently contributes to somite formation in a periodic way. Whether there exists a critical factor coordinating Fgf8 and Notch signaling pathways is largely unknown. Here, we demonstrate that the loss of function of geminin gave rise to narrower somites as a result of derepressed Fgf8 gradient in the PSM and tail bud. Furthermore, in geminin morphants, the somite boundary could not form properly but the oscillation of cyclic genes was normal, displaying the blurry somitic boundary and disturbed somite polarity along the AP axis. In mechanism, these manifestations were mediated by the disrupted association of the geminin/Brg1 complex with intron 3 of mib1. The latter interaction was found to positively regulate mib1 transcription, Notch activity, and sequential somite segmentation during somitogenesis. In addition, geminin was also shown to regulate the expression of deltaD in mib1-independent way. Collectively, our data for the first time demonstrate that geminin regulates Fgf8 and Notch signaling to regulate somite segmentation during somitogenesis.
Renal Cell Carcinoma in a Horseshoe Kidney Treated with Laparoscopic Partial Nephrectomy
Authors: Ohtake Shinji , Kawahara Takashi , Noguchi Go , Nakaigawa Noboru , Chiba Kimio , Uemura Hiroji , Yao Masahiro , Makiyama Kazuhide
Published: June 2018

Introduction.Horseshoe kidney is one of the most common congenital renal fusion anomalies. Due to its poor mobility and abnormal vasculature form, surgeons should pay close attention to all anatomical variations.Case Presentation.An 83-year-old woman was referred to our hospital because of left renal tumor in a horseshoe kidney incidentally found by her previous hospital. We performed laparoscopic partial nephrectomy. The pathological diagnosis was clear cell renal cell carcinoma. G2 INFαV-pT1a with a negative surgical margin. No evidence of recurrence has been noted, and the renal function is well preserved at 28 months after surgery.Conclusion.When performing laparoscopic partial nephrectomy for renal carcinoma, especially a horseshoe kidney, preoperative imaging is crucial for identifying the location of the renal vessels.