bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics of non-randomised studies using comparisons with external controls submitted for regulatory approval in the USA and Europe: a systematic review
Authors: Goring Sarah , Taylor Aliki , Müller Kerstin , Li Tina Jun Jian , Korol Ellen E , Levy Adrian R , Freemantle Nick
Published: February 2019

Objectives

Non-randomised clinical trial designs involving comparisons against external controls or specific standards can be used to support regulatory submissions for indications in diseases that are rare, with high unmet need, without approved therapies and/or where placebo is considered unethical. The objective of this review was to summarise the characteristics of non-randomised trials submitted to the European Medicines Agency (EMA) or Food and Drug Administration (FDA) for indications in haematological cancers, haematological non-malignant conditions, stem cell transplants or rare metabolic diseases.

Methods

We conducted systematic searches of EMA databases of conditional approvals, exceptional circumstances, or orphan drug designations and FDA inventories of orphan drug designations, accelerated approvals, breakthrough therapy, fast-track and priority approvals. Products were included if reviewed by at least one agency between 2005 and 2017, the primary evidence base was non-randomised trial(s) and the indication was for haematological cancers, stem cell transplantation, haematological conditions or rare metabolic conditions.

Results

We identified 43 eligible indication-specific products using non-randomised study designs involving comparisons with external controls, submitted to the EMA (n=34) and/or FDA (n=41). Of the 43 indication-specific products, 4 involved matching external controls to the population of a non-randomised interventional study using individual patient-level data (IPD), 12 referred to external controls without IPD and 27 did not explicitly reference external controls. The FDA approved 98% of submissions, with 56% accelerated approvals; most required postapproval confirmatory randomised controlled trials (RCT). The EMA approved 79% of submissions, with a quarter of approvals conditional on completion of a postapproval RCT or additional non-randomised trials.

Conclusions

There has been a large increase in submissions to the EMA and FDA using non-randomised study designs involving comparisons with external controls in recent years. This study demonstrated that regulators may be willing to approve such submissions, although approvals are often conditional on further confirmatory evidence from postapproval studies.
A qualitative study exploring how routinely collected Medication Safety Thermometer data have been used for quality improvement purposes using case studies from three UK hospitals
Authors: Rostami Paryaneh , Harrison Abigail , Parry Gareth , Ashcroft Darren , Tully Mary P
Published: February 2019

Objectives

The Medication Safety Thermometer (MedsST) is a medication safety data collection tool, which has been used by over 100 UK healthcare organisations to enable measurement of medication safety for improvement purposes. This study aimed to explore whether, and how, data collected by the MedsST have been used in organisations to facilitate medication safety improvements.

Design

Routine MedsST data collected between October 2013 and July 2016 were analysed using Run charts. Identified changes were investigated using interviews with staff from each hospital trust. The interviews were analysed using a framework based on Normalisation Process Theory, focusing on use of the MedsST and its data.

Setting

Three National Health Service hospital trusts in the North West of England, which have used the MedsST for the longest period.

Participants

Eight interview participants, purposely sampled based on their involvement with the MedsST, included pharmacists, pharmacy technicians and nurses.

Results

Improvement was often at ward level and focused on particular areas of medication safety, led by clinical champions. The most sustainable improvements involved changes to systems, such as introducing new guidelines. Although some improvement occurred, internal communication about improvements was poor, and large amounts of data remained unused, often due to a lack of ownership of data review and use.

Conclusions

Simply collecting data is not sufficient; a system of data collection, review and use for improvement is required. Issues with such systems may have been recognised and averted if implementation theory had been used in the early stages of national development and implementation. However, implementation theory could be used within organisations to fix issues locally, particularly to increase ward-level ownership of this system, which could lead to considerable improvements.
GP retention in the UK: a worsening crisis. Findings from a cross-sectional survey
Authors: Owen Katherine , Hopkins Thomas , Shortland Thomas , Dale Jeremy
Published: February 2019

Objective

To investigate how recent national policy-led workforce interventions are affecting intentions to remain working as a general practitioner (GP).

Design

Online questionnaire survey with qualitative and quantitative questions.

Setting and participants

All GPs (1697) in Wessex region, an area in England for which previous GP career intention data from 2014 is available.

Results

929 (54.7%) participated. 59.4% reported that morale had reduced over the past two years, and 48.5% said they had brought forward their plans to leave general practice. Intention to leave/retire in the next 2 years increased from 13% in the 2014 survey to 18% in October/November 2017 (p=0.02), while intention to continue working for at least the next 5 years dropped from 63.9% to 48.5% (p<0.0001). Age, length of service and lower job satisfaction were associated with intention to leave. Work intensity and amount were the most common reasons given for intention to leave sooner than previously planned; 51.0% participants reported working more hours than 2 years previously, predominantly due to increased workload.

GPs suggested increased funding, more GPs, better education of the public and expanding non-clinical and support staff as interventions to improve GP retention.

National initiatives that aligned with these priorities, such as funding to expand practice nursing were viewed positively, but low numbers of GPs had seen evidence of their roll-out. Conversely, national initiatives that did not align, such as video consulting, were viewed negatively.

Conclusion

While recent initiatives may be having an impact on targeted areas, most GPs are experiencing little effect. This may be contributing to further lowering of morale and bringing forward intentions to leave. More urgent action appears to be needed to stem the growing workforce crisis.
Risk perception, beliefs about medicines and medical adherence among pregnant and breastfeeding women with migraine: findings from a cross-sectional study in Norway
Authors: Amundsen Siri , Øvrebø Torunn Gudmestad , Amble Netta Marie Skretteberg , Poole Anne Christine , Nordeng Hedvig
Published: February 2019

Objectives

To examine risk perception, beliefs about migraine medications and medical adherence among pregnant and breastfeeding women with migraine.

Design and setting

Cross-sectional study conducted in Norway from October 2013 to February 2014. Data were collected via an anonymous, electronic questionnaire.

Participants

Women with migraine, either pregnant or having delivered within the previous 18 months.

Main outcomes

Women’s perception of teratogenic risk (numeric rating scale 0–10) was obtained for 14 different drugs/substances, including medications commonly used in the acute treatment of migraine. Women’s perspectives on migraine drug therapy were assessed by 10 statements from the Beliefs about Medicines Questionnaire (BMQ-Specific) and six pregnancy/breastfeeding-specific statements. Adherence to migraine treatment during pregnancy and breastfeeding period was assessed by maternal self-report.

Results

The study population included 401 women with migraine, of which 140 were pregnant and 261 were new mothers. More than 70% of the women reported use of migraine medications during pregnancy. Still, the majority severely overestimated the risk associated with migraine medications and were concerned about using medications to manage their migraine during pregnancy and breastfeeding. Almost 9 out of 10 women had at some point deliberately avoided using migraine medications during their pregnancy. Women reporting use of migraine medications, however, were more positive and overestimated to a lesser extent the risks of using such medications in pregnancy compared with their counterparts.

Conclusions

Women with migraine severely overestimated the risk associated with migraine pharmacotherapy in pregnancy. The majority of women were concerned about use of migraine medications during pregnancy and breastfeeding and reported non-adherence to needed treatment. More attention should be focused on women’s beliefs and concerns regarding migraine pharmacotherapy during pregnancy and breastfeeding in order to improve management of disease, reduce unfounded concerns and enhance adherence to needed treatment.
Haematologists and palliative care: a multicentric qualitative study
Authors: Tricou Colombe , Munier Sophie , Phan-Hoang Nicolas , Albarracin Dolores , Perceau-Chambard Élise , Filbet Marilene
Published: February 2019

Objectives

Early palliative care leads to meaningful improvements in physical and psychosocial symptoms, as well as quality of life, in patients with advanced cancer. Patients with haematological malignancies, despite a high level of distress, continue to have less access to palliative care services. The aim of this study was to identify haematologists’ perceptions of palliative care, as well as barriers to patient referral.

Methods

We used a qualitative grounded theory methodology. Twenty-four medical haematologists involved in clinical practice from two French centres in Lyon—the Lyon Sud University Hospital and the Léon Bérard Cancer Center—were included. The interview guide questions aimed to establish the clinical situations which triggered referral to palliative care and how participants perceived palliative care.

Results

Data saturation was reached after 14 interviews. The data analysis highlighted four themes. The aim of palliative care was clearly identified as alleviating severe suffering. Palliative care was identified as a separate specialty, and respondents expressed the need for collaboration. Early intervention was perceived as beneficial to avoid certain situations such as hospitalisation or emergency department visits at the end of life. The main barrier to palliative care referral remained the negative connotations associated with the term ‘palliative’, which was overwhelmingly associated with the end of life.

Significance of results

Our results suggest that the principal barrier to palliative care referral is the term ‘palliative care’; haematologists would prefer ‘supportive care’ instead.
Multicentre randomised controlled trial comparing standard and high resolution optical technologies in colorectal cancer screening
Authors: Di Caro Simona , Fini Lucia , Vega Roser , Fragkos Konstantinos C , Dolwani Sunil , Green John , Smith Lesley-Ann , Beckett Conrad , Cameron Ewen , Banks Matthew
Published: February 2019

Background and objectives

The UK bowel cancer screening programme (BCSP) has been established for the early detection of colorectal cancer offering colonoscopy to patients screened positive by faecal occult blood tests. In this multisite, prospective, randomised controlled trial, we aimed to compare the performance of Standard Definition Olympus Lucera (SD-OL) with Scope Guide and the High Definition Pentax HiLine (HD-PHL).

Patients and methods

Subjects undergoing a colonoscopy as part of the UK National BCSP at four UK sites were randomised to an endoscopy list run using either SD-OL or HD-PHL. Primary endpoints were polyp and adenoma detection rate (PDR and ADR, respectively) as well as polyp size, morphology and histology characteristics.

Results

262 subjects (168 males, mean age 66.3±4.3 years) were colonoscoped (133 patients with HD-PHL while 129 with SD-OL). PDR and ADR were comparable within the two optical systems. The HD-PHL group resulted in a PDR 55.6% and ADR 43.6%; the SD-OL group had PDR 56.6% and ADR 45.7%. HD-PHL was significantly superior to SD-OL in detection of flat adenomas (18.6% vs 5.2%, p<0.001), but not detection of pedunculated or sessile polyps. Patient comfort, use of sedation and endoscopist perception of procedural difficulty resulted similar despite the use of Scope Guide with SD-OL.

Conclusion

PDR and ADR were not significantly different between devices. The high-resolution colonoscopy system HD-PHL may improve polyp detection as compared with standard resolution technology in detecting flat adenomas. This advantage may have clinically significant implications for missed lesion rates and post-colonoscopy interval colorectal cancer rates.
European Stroke Organisation (ESO) - European Society for Minimally Invasive Neurological Therapy (ESMINT) Guidelines on Mechanical Thrombectomy in Acute Ischemic Stroke
Authors: Turc Guillaume , Bhogal Pervinder , Fischer Urs , Khatri Pooja , Lobotesis Kyriakos , Mazighi Mikaël , Schellinger Peter D. , Toni Danilo , de Vries Joost , White Philip , Fiehler Jens
Published: February 2019

Background

Mechanical thrombectomy (MT) has become the cornerstone of acute ischemic stroke management in patients with large vessel occlusion (LVO).

Objective

To assist physicians in their clinical decisions with regard toMT.

Methods

These guidelines were developed based on the standard operating procedure of the European Stroke Organisation and followed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. An interdisciplinary working group identified 15 relevant questions, performed systematic reviews and meta-analyses of the literature, assessed the quality of the available evidence, and wrote evidence-based recommendations. Expert opinion was provided if not enough evidence was available to provide recommendations based on the GRADE approach.

Results

We found high-quality evidence to recommend MT plus best medical management (BMM, including intravenous thrombolysis whenever indicated) to improve functional outcome in patients with LVO-related acute ischemic stroke within 6 hours after symptom onset. We found moderate quality of evidence to recommend MT plus BMM in the 6–24h time window in patients meeting the eligibility criteria of published randomized trials. These guidelinesdetails aspects of prehospital management, patient selection based on clinical and imaging characteristics, and treatment modalities.

Conclusions

MT is the standard of care in patients with LVO-related acute stroke. Appropriate patient selection and timely reperfusion are crucial. Further randomized trials are needed to inform clinical decision-making with regard tothe mothership and drip-and-ship approaches, anesthaesia modalities during MT, and to determine whether MT is beneficial in patients with low stroke severity or large infarct volume.
Efficacy and reliability of active robotic-assisted total knee arthroplasty compared with conventional total knee arthroplasty: a systematic review and meta-analysis
Authors: Ren Yi , Cao Shiliang , Wu Jinxuan , Weng Xisheng , Feng Bin
Published: February 2019

Background

In the field of prosthetics, the ultimate goal is to improve the clinical outcome by using a technique that prolongs the longevity of prosthesis. Active robotic-assisted total knee arthroplasty (TKA) is one such technique that is capable of providing accurate implant position and restoring mechanical alignment. Although relevant studies have been carried out, the differences in the efficacy and reliability between active robotic-assisted TKA and conventional arthroplasty have not yet been adequately discussed.

Methods

We referenced articles, including randomised controlled trials and comparative retrospective research, from PubMed, Embase, Cochrane Library and Web of Science, in order to compare active robotic-assisted TKA with the conventional technique. Data extraction and quality assessment were conducted for each study. Statistical analysis was performed using Revman V. 5.3.

Results

Seven studies with a total of 517 knees undergoing TKA were included. Compared with conventional surgery, active robotic TKA showed better outcomes in precise mechanical alignment (mean difference, MD: − 0.82, 95% CI: −1.15 to − 0.49, p < 0.05) and implant position, with lower outliers (p < 0.05), better functional score (Western Ontario and McMaster University, Knee Society Score functional score) and less drainage (MD: − 293.28, 95% CI: − 417.77 to − 168.79, p < 0.05). No significant differences were observed when comparing the operation time, range of motion and complication rates.

Conclusion

The current research demonstrates that active robotic-assisted TKA surgeries are more capable of improving mechanical alignment and prosthesis implantation when compared with conventional surgery. Further studies are required to investigate the potential benefits and long-term clinical outcomes of active robotic-assisted TKA.
Mechanical stress-induced mast cell degranulation activates TGF-β1 signalling pathway in pulmonary fibrosis
Authors: Shimbori Chiko , Upagupta Chandak , Bellaye Pierre-Simon , Ayaub Ehab A , Sato Seidai , Yanagihara Toyoshi , Zhou Quan , Ognjanovic Alexander , Ask Kjetil , Gauldie Jack , Forsythe Paul , Kolb Martin R J
Published: February 2019

Background

The role of mast cells accumulating in idiopathic pulmonary fibrosis (IPF) lungs is unknown.

Objectives

We investigated the effect of fibrotic extracellular matrix (ECM) on mast cells in experimental and human pulmonary fibrosis.

Results

In IPF lungs, mast cell numbers were increased and correlated with disease severity (control vs 60%<FVC<90%, mean difference=-222.7, 95% CI −386.3 to −59.2, p=0.004; control vs FVC<60%, mean difference=−301.7, 95% CI of difference −474.1 to −129.34, p=0.0001; FVC>90% vs 60%<FVC<90%, mean difference=−189.6, 95% CI of difference −353.1 to −26.03, p=0.017; FVC>90% vs FVC<60%, mean difference=−268.6, 95% CI of difference −441.0 to −96.17, p=0.0007). Plasma tryptase levels were increased in IPF and negatively correlated with FVC (control vs FVC<60%, mean difference=−17.12, 95% CI of difference −30.02 to −4.22, p=0.006: correlation curves R=−0.045, p=0.025). In a transforming growth factor (TGF)-β1-induced pulmonary fibrosis model, chymase-positive and tryptase-positive mast cells accumulated in fibrotic lung. Lung tissue was decellularised and reseeded with bone marrow or peritoneum-derived mast cells; cells on fibrotic ECM released more TGF-β1 compared with normal ECM (active TGF-β1: bone marrow-derived mast cell (BMMC)-DL vs BMMC-TGF-β1 p=0.0005, peritoneal mast cell (PMC)-DL vs PMC-TGF-β1 p=0.0003, total TGF-β1: BMMC-DL vs BMMC-TGF-β1 p=0.013, PMC-DL vs PMC-TGF-β1 p=0.001). Mechanical stretch of lungs caused mast cell degranulation; mast cell stabilisers inhibited degranulation (histamine: cont vs doxantrazole p=0.004, β-hexosaminidase: cont vs doxantrazole, mean difference=1.007, 95% CI of difference 0.2700 to 1.744, p=0.007) and TGF-β1 activation (pSmad2/Smad2: cont vs dox p=0.006). Cromoglycate attenuated pulmonary fibrosis in rats (collagen: phosphate-buffered saline (PBS) vs cromoglycate p=0.036, fibrotic area: PBS vs cromoglycate p=0.031).

Conclusion

This study suggests that mast cells may contribute to the progression of pulmonary fibrosis.
Electrochemotherapy as treatment for generalised squamous cell carcinoma in a dog
Authors: Boncea Ana Maria , Cristea Anca , Bourdeau Patrick
Published: February 2019

Canine squamous cell carcinoma (cSCC) is the second most common cutaneous neoplasm in dogs. Treatment options are limited. Electrochemotherapy (ECT) has been proposed as an alternative treatment for many types of tumours. To describe the use of ECT as treatment for generalised cSCC. An adult dog (four years old) was diagnosed with generalised cSCC. There were 24 tumours with the size range of 0.3–3 cm. The biopsy revealed an infiltrate rich in epithelial squamous cells, associated with pyogranulomatous inflammation. ECT was elected as treatment of choice. Cisplatin was injected intratumorously. After five minutes, the electric pulses were applied. The complete tumour regression was noted four weeks after. The dog was still in complete remission, 20 months later. This is the first case reporting a complete long‐term remission using ECT for generalised cSCC.
Propagators of the Dirac fermions on spatially flat FLRW space–times
Authors: Cotăescu Ion I.
Published: February 2019

The general formalism of the free Dirac fermions on spatially flat (1[Formula: see text]+[Formula: see text]3)-dimensional Friedmann-Lemaître–Robertson–Walker (FLRW) space–times is developed in momentum representation. The mode expansions in terms of the fundamental spinors satisfying the charge conjugation and normalization conditions are used for deriving the structure of the anticommutator matrix-functions and, implicitly, of the retarded, advanced, and Feynman fermion propagators. The principal result is that the new type of integral representation we proposed recently in the de Sitter case can be applied to the Dirac fermions in any spatially flat FLRW geometry. Moreover, the Dirac equation of the left-handed massless fermions can be analytically solved finding a general spinor solution and deriving the integral representations of the neutrino propagators. It is shown that in the Minkowski flat space–time our new integral representation is up to a change of variable just like the usual Fourier representation of the fermion propagators. The form of the Feynman propagator of the massive fermions on a spatially flat FLRW space–time with a scale factor of Milne-type is also outlined.
Ab initiostudy of electronic and optical properties of nitrogen-doped rutile TiO2
Authors: Olayinka A. S. , Adetunji B. I. , Idiodi J. O. A. , Aghemelon U.
Published: February 2019

Ab initio study has been carried out to investigate the band structure, density of state and optical dielectric function of pure and Nitrogen (N)-doped rutile phase of TiO2. The band structure obtained with the inclusion of U parameter of 8.5 eV compared favorably with experimental result. Bandgap of N-doped rutile decreases with respect to pure rutile which is traceable to 2p state of the Nitrogen dopant as revealed in partial density of state (PDOS). The optical properties calculated revealed that N-doped rutile has at least one optical peak in the visible light region of the electromagnetic spectrum which suggests it to be a potential material for photovoltaic application than pure rutile. Our results suggest that optical properties of rutile can be adapted by doping with Nitrogen at different concentration which enhances its potential as photocatalyst.
Stress and frequency analysis of silicon diaphragm of MEMS based piezoresistive pressure sensor
Authors: Samridhi  , Kumar Manish , Dhariwal Sachin , Singh Kulwant , Alvi P. A.
Published: February 2019

This paper reports the stress and frequency analysis of dynamic silicon diaphragm during the simulation of micro-electro-mechanical-systems (MEMS) based piezoresistive pressure sensor with the help of finite element method (FEM) within the frame work of COMSOL software. Vibrational modes of rectangular diaphragm of piezoresistive pressure sensor have been determined at different frequencies for different pressure ranges. Optimal frequency range for particular applications for any diaphragm is a very important so that MEMS sensors performance should not degrade during the dynamic environment. Therefore, for the MEMS pressure sensor having applications in dynamic environment, the diaphragm frequency of 280 KHz has been optimized for the diaphragm thickness of 50 [Formula: see text]m and hence this frequency can be considered for showing the better piezoresistive effect and high sensitivity. Moreover, the designed pressure sensor shows the high linearity and enhanced sensitivity of the order of ([Formula: see text]0.5066 mV/psi).
Development of a microchip based on LIGA technology for bacterial inactivation
Authors: Li Hua , Yun Hongmei , Jiang Liuxiu , Zeng Ruosheng , Chen Yanlin , Deng Minchao , Liu Chunhua , Xiao Wenxiang , Jiang Yongrong , Chen Zhencheng
Published: February 2019

We designed and fabricated a new micro-needle-column discharge chip by Lithographie, Galvanoformung and Abformung technology to meet sterilization requirements. The dimensions of the chip are 11.6 mm × 11.7 mm × 3 mm. The micro-discharge structure is composed of a needle electrode and two cylinder electrodes. We employed a needle with a tip diameter of 20 [Formula: see text]m and a thickness of 20 [Formula: see text]m as the discharge cathode. We used a cylinder with a thickness of 1 mm and diameter of 0.4 mm as the anode. We carried out the gas discharge experiments in ambient air and at room temperature, without external air flow. In the experiments, a corona and glow discharge with applied voltages of −2.1 kV and −3.8 kV were realized. We carried out the sterilization experiments for six different discharge times (15, 30, 60, 90, 120 and 180 s) with an applied voltage of −3.8 kV. The inactivation efficiency of Escherichia coli and Staphylococcus aureus reached 100% for sterilization times of 120 s and 180 s. This indicates that the micro-needle-column discharge chip may be suitable as a portable sterilizer.
Leader formation with mean-field birth and death models
Authors: Albi Giacomo , Bongini Mattia , Rossi Francesco , Solombrino Francesco
Published: February 2019

We provide a mean-field description for a leader–follower dynamics with mass transfer among the two populations. This model allows the transition from followers to leaders and vice versa, with scalar-valued transition rates depending nonlinearly on the global state of the system at each time. We first prove the existence and uniqueness of solutions for the leader–follower dynamics, under suitable assumptions. We then establish, for an appropriate choice of the initial datum, the equivalence of the system with a PDE–ODE system, that consists of a continuity equation over the state space and an ODE for the transition from leader to follower or vice versa. We further introduce a stochastic process approximating the PDE, together with a jump process that models the switch between the two populations. Using a propagation of chaos argument, we show that the particle system generated by these two processes converges in probability to a solution of the PDE–ODE system. Finally, several numerical simulations of social interactions dynamics modeled by our system are discussed.
Immersogeometric analysis of compressible flows with application to aerodynamic simulation of rotorcraft
Authors: Xu Fei , Bazilevs Yuri , Hsu Ming-Chen
Published: February 2019

We present an immersogeometric analysis (IMGA) approach for the simulation of compressible flows around complex geometries. In this method, compressible flow simulations are performed directly on various boundary representations (B-reps) of mechanical designs, circumventing the labor-intensive and time-consuming cleanup of complex geometric models. A new formulation for the weak imposition of essential boundary conditions in the context of non-body-fitted meshes is proposed. The formulation employs the non-symmetric Nitsche method, which yields good performance especially when the penalty parameters are difficult to estimate. We test the proposed immersogeometric formulation on benchmark problems for a wide range of Reynolds and Mach numbers, showing its robustness and accuracy. Finally, the methodology is applied to the simulation of a UH-60 Black Hawk helicopter in forward flight, illustrating the ability of the proposed approach to support the design of real-world engineering systems through high-fidelity aerodynamic analysis.
Seismic Stability Sensitivity and Uncertainty Analysis of a High Arch Dam-Foundation System
Authors: Liang Hui , Guo Shengshan , Tu Jin , Li Deyu
Published: February 2019

Parameter uncertainty associated with concrete arch dams always arises from modeling assumptions and the lack of knowledge or information of the engineering geological situations, especially in the seismic stability analysis of arch dams. In this research, a high arch dam is selected as a case study for probabilistic analysis of the seismic stability performance. The arch dam abutment and the dam are coupled as a system. A comprehensive approach considering contraction joints, boundaries of the probable sliding rock mass and the dam-foundation interface is presented. The contact nonlinearity is solved by using the dynamic contact model with Lagrange multiplier method. The main parameters of the probable sliding block are considered as random variables containing the friction coefficients and cohesions. Both the slippage and sliding area ratio are chosen as the engineering demand parameters (EDP). The sensitivity analysis is performed to reveal the relative influence of each parameter separately by the approximate incremental dynamic analysis (IDA) method. The friction coefficients are shown to be more crucial than the cohesions on the dam’s resistance to seismic instability. The sliding area ratio can be better used for unveiling the sliding process of the arch dam of concern, while the slippage is useful for one to judging the stability of the arch dam under seismic hazards. The Latin hypercube sampling (LHS) with approximate moment estimation is used to investigate the parameter uncertainty to the seismic stability performance of the high arch dam. The results provide a useful reference for using the median/mean-parameter model to accurately estimate the median/mean response of the dam.
Cohen–Macaulay modifications of the facet ideal of a simplicial complex
Authors: Ahmad Safyan , Anwar Imran , Kosar Zunaira
Published: February 2019

We define the chordal simplicial complex by using the definition of chordal clutter introduced by Woodroofe. We show that the facet ideal of the chordal simplicial complex is Cohen–Macaulay if and only if it is unmixed. Moreover, we prove that the facet ideal of a chordal simplicial complex has infinitely many nontrivial Cohen–Macaulay modifications.
An Effective Grouping Evolution Strategy Algorithm Enhanced with Heuristic Methods for Assembly Line Balancing Problem
Authors: Nejad Mazyar Ghadiri , Kashan Ali Husseinzadeh
Published: February 2019

Assembly line balancing problem (ALBP) is an allocation of given tasks to the workstations in a way that the number of workstations or the idle times of workstations get minimized. ALBP is a well-known problem in mass-production systems with high production volume and low diversity. In division and grouping allocation problems like ALBP, metaheuristic algorithms based on group structure, i.e. grouping genetic algorithm, are more efficient. The aim of this study is developing a new solution procedure to minimize the number of workstations for a given cycle time based on grouping evolution strategy. A modification of the ranked positional weight method is proposed to construct the initial solution, and a new heuristic method based on a modified version of the COMSOAL method is provided to tighten the solution after performing the mutation operator. Different strategies based on line efficiency and line smoothness indexes are considered to select the best result and transfer it to the next generation. Moreover, to evaluate the performance of proposed algorithms, some well-known standard test problems are utilized. Computational results indicate that the proposed solution algorithm performs efficiently and can obtain the optimal global solution in most of the high dimensional problems.
Use case repository framework based on machine learning algorithm to analyze the software development estimation with intelligent information systems
Authors: Lalitha R. , Latha B. , Sumathi G.
Published: February 2019

The success of information system process depends on accuracy of software estimation. Estimation is done at initial phase of software development. It requires a collection of all relevant required information for estimating the software effort. In this paper, a methodology is proposed to maintain a knowledgeable use case repository to store the use cases of various projects in several software project-related domains. This acts as a reference model to compare similar use cases of similar types of projects. The use case points are calculated and using this, schedule estimation and effort estimation of a project are calculated using the formulas of software engineering. These values are compared with the estimated effort and scheduled effort of a new project under development. Apart from these, the effective machine learning technique called neural network is used to measure how accurately the information is processed by use of case repository framework. The proposed machine learning-based use case repository system helps to estimate and analyze the effort using the machine learning algorithms.
On a nonlocal asymmetric Kirchhoff problem
Authors: Hamdani Mohamed Karim
Published: February 2019

This work is devoted to study the existence of nontrivial solutions to nonlocal asymmetric problems involving the [Formula: see text]-Laplacian. [Formula: see text] where [Formula: see text] is a bounded domain with smooth boundary, [Formula: see text] is a Kirchhoff function, [Formula: see text] and [Formula: see text] is of subcritical polynomial or subcritical exponential growth. Moreover, the existence of nontrivial solutions for the above problem is obtained by using variational methods combined with the Moser–Trudinger inequality. Our interest then is to study [Formula: see text] without the analogue of Ambrosetti–Rabinowitz superquadratic condition ([Formula: see text] condition for short) in the positive semi-axis. To the best of our best knowledge, our results are new even in the asymmetric Kirchhoff Laplacian and [Formula: see text]-Laplacian cases.
Automorphism groups of semigroups of upfamilies
Authors: Gavrylkiv Volodymyr M.
Published: February 2019

A family [Formula: see text] of nonempty subsets of a set [Formula: see text] is called an upfamily if for each set [Formula: see text] any set [Formula: see text] belongs to [Formula: see text]. The extension [Formula: see text] of [Formula: see text] consists of all upfamilies on [Formula: see text]. Any associative binary operation [Formula: see text] can be extended to an associative binary operation [Formula: see text]. In the paper, we study automorphisms of extensions of groups, finite monogenic semigroups, null semigroups, right zero semigroups and left zero semigroups. Also, we describe the automorphism groups of extensions of some semigroups of small cardinalities.
Generalized multiplication operators of higher order on weighted Hardy spaces
Authors: Datt Gopal , Jain Mukta
Published: February 2019

In the present paper, the notion of generalized multiplication operators on weighted Hardy spaces is extended along with the description of its properties. The symbols inducing normal and compact generalized multiplication operators of higher order are identified. The commutativity of these operators with composition operators is also described.
On the lattice of biorder ideals of regular rings
Authors: Akhila R. , Romeo P. G.
Published: February 2019

The study of biordered set plays a significant role in describing the structure of a regular semigroup and since the definition of regularity involves only the multiplication in the ring, it is natural that the study of semigroups plays a significant role in the study of regular rings. Here, we extend the biordered set approach to study the structure of the regular semigroup [Formula: see text] of a regular ring [Formula: see text] by studying the idempotents [Formula: see text] of the regular ring and show that the principal biorder ideals of the regular ring [Formula: see text] form a complemented modular lattice and certain properties of this lattice are studied.
Novel entropy estimators of a continuous random variable
Authors: Al-Omari Amer Ibrahim , Haq Abdul
Published: February 2019

This paper presents some novel entropy estimators of a continuous random variable using simple random sampling (SRS), ranked set sampling (RSS), and double RSS (DRSS) schemes. The theoretical results of the proposed entropy estimators are derived. The proposed entropy estimators are compared in terms of the bias and the root mean squared errors, theoretically and numerically, with the Vasicek O. [A test for normality based on sample entropy, J. R. Stat. Soc. B 38:54–59, 1976.] entropy estimators using SRS, RSS, and DRSS schemes. It turns out that the new novel entropy estimators are substantially better than the existing Vasicek’s entropy estimators.
Response of Middle Jurassic shallow-marine environments to syn-depositional block tilting: Isles of Skye and Raasay, NW Scotland
Authors: Archer Stuart G. , Steel Ronald J. , Mellere Donatella , Blackwood Stuart , Cullen Brian
Published: February 2019

The Hebridean Province of NW Scotland provides insight into the interaction between tectonics and shallow-marine and tidal strait depositional environments in the Sea of the Hebrides and Inner Hebrides basins. The study tests the influence of syn-depositional block tilting on gross thickness, sand to mud ratio and the distribution of shallow-marine facies in the resulting succession. New Middle Jurassic palaeogeographical maps and stratigraphic correlations are presented that integrate both outcrop and well data and illustrate the evolution of the deltaic sedimentary system in a broad, semi-regional context.

Results show that distance from the sediment entry point and the syn-rift tectonic geomorphology were the critical controls on gross thickness, sand to mud ratios and facies types. The impact of relative sea-level change is hard to detect in locations proximal to the Scottish hinterland, where sediment supply was large relative to accommodation (Ss > Ac), but becomes more influential in distal locations where eustasy and tectonic subsidence convolved to increase the influence of accommodation over sediment supply (Ac > Ss).

Supplementary material:
An outcrop to well log correlation exercise is available at
https://doi.org/10.6084/m9.figshare.c.4397858
Hexedriocystis
, an aberrant echinoderm from the Upper Ordovician of Morocco
Authors: Zamora Samuel , Sumrall Colin D.
Published: February 2019

Hexedriocystis
is a very unusual echinoderm with a puzzling combination of morphological features. The two described species
H. inexpectatus
and
H. mimus
occur in Upper Ordovician siliciclastic rocks from Morocco, North Africa. They show a striking combination of isorophid edrioasteroid, paedomorphic crinoid and blastozoan characteristics including a domed thecal shape with a peripheral rim-like attachment structure, imbricate thecal plates. However, both species developed feeding appendages covered by large peristomial cover plates and six oral plates.
Hexedriocystis
lived intimately associated with edrioasteroid colonies and its strange morphology is probably the result of convergence with isorophid edrioasteroid.
How Understandable Are Pattern-based Behavioral Constraints for Novice Software Designers?
Authors: Czepa Christoph , Zdun Uwe
Published: February 2019

This article reports a controlled experiment with 116 participants on the understandability of representative graphical and textual pattern-based behavioral constraint representations from the viewpoint of novice software designers. Particularly, graphical and textual behavioral constraint patterns present in the declarative business process language
Declare
and textual behavioral constraints based on
Property Specification Patterns
are the subjects of this study. In addition to measuring the understandability construct, this study assesses subjective aspects such as perceived difficulties regarding learning and application of the tested approaches. An interesting finding of this study is the overall low achieved correctness in the experimental tasks, which seems to indicate that pattern-based behavioral constraint representations are hard to understand for novice software designers in the absence of additional supportive measures. The results of the descriptive statistics regarding achieved correctness are slightly in favor of the textual representations, but the inference statistics do not indicate any significant differences in terms of understandability between graphical and textual behavioral constraint representations.
Glucose and amino acid metabolism in mice depend mutually on glucagon and insulin receptor signaling
Authors: Galsgaard Katrine D. , Winther-Sørensen Marie , Pedersen Jens , Kjeldsen Sasha A. S. , Rosenkilde Mette M. , Wewer Albrechtsen Nicolai J. , Holst Jens J.
Published: February 2019

Glucagon and insulin are important regulators of blood glucose. The importance of insulin receptor signaling for alpha-cell secretion and of glucagon receptor signaling for beta-cell secretion is widely discussed and of clinical interest. Amino acids are powerful secretagogues for both hormones, and glucagon controls amino acid metabolism through ureagenesis. The role of insulin in amino acid metabolism is less clear. Female C57BL/6JRj mice received an insulin receptor antagonist (IRA) (S961; 30 nmol/kg), a glucagon receptor antagonist (GRA) (25-2648; 100 mg/kg), or both GRA and IRA (GRA + IRA) 3 h before intravenous administration of similar volumes of saline, glucose (0.5 g/kg), or amino acids (1 µmol/g) while anesthetized with isoflurane. IRA caused basal hyperglycemia, hyperinsulinemia, and hyperglucagonemia.Unexpectedly, IRA lowered basal plasma concentrations of amino acids, whereas GRA increased amino acids, lowered glycemia, and increased glucagon but did not influence insulin concentrations. After administration of GRA + IRA, insulin secretion was significantly reduced compared with IRA administration alone. Blood glucose responses to a glucose and amino acid challenge were similar after vehicle and GRA + IRA administration but greater after IRA and lower after GRA. Anesthesia may have influenced the results, which otherwise strongly suggest that both hormones are essential for the maintenance of glucose homeostasis and that the secretion of both is regulated by powerful negative feedback mechanisms. In addition, insulin limits glucagon secretion, while endogenous glucagon stimulates insulin secretion, revealed during lack of insulin autocrine feedback. Finally, glucagon receptor signaling seems to be of greater importance for amino acid metabolism than insulin receptor signaling.
Development of a Predictive Model of Difficult Hemostasis following Endobronchial Biopsy in Lung Cancer Patients
Authors: Wang Saibin
Published: February 2019

Endobronchial biopsy (EBB)-induced bleeding is fairly common; however, it can be potentially life-threatening due to difficult hemostasis following EBB. The aim of this study was to develop a predictive model of difficult hemostasis post-EBB. A total of 620 consecutive patients with primary lung cancer who had undergone EBB between 2014 and 2018 in a large tertiary hospital were enrolled in this retrospective single-center cohort study. Patients were classified into the difficult hemostasis group and the nondifficult hemostasis group according to hemostatic measures used following EBB. The LASSO regression method was used to select predictors and multivariate logistic regression was applied to develop the predictive model. The area under the curve (AUC) of the model was calculated. Bootstrapping method was applied for internal validation. Calibration curve analysis and decision curve analysis (DCA) were also performed. A nomogram was constructed to display the model. The incidence of difficult hemostasis post-EBB was 11.9% (74/620). Eight variables were selected by the LASSO regression analysis and seven (histological type of cancer, lesion location, neutrophil percentage, activated partial thromboplastin time, low density lipoprotein cholesterol, apolipoprotein-E, and pulmonary infection) of them were finally included in the predictive model. The AUC of the model was 0.822 (95% CI, 0.777-0.868), and it was 0.808 (95% CI, 0.761-0.856) in the internal validation. The predictive model was well calibrated and DCA indicated its potential clinical usefulness, which suggests that the model has great potential to predict lung cancer patients with a more difficult post-EBB hemostasis.
Novel Use of Silicone Sheets for Immediate Implant Placement in Fresh Molar Extraction Sockets
Authors: Lee Won-Pyo , Choi Jae-Heung , Yu Sang-Joun , Kim Byung-Ock
Published: February 2019

In the recent years, the immediate placement of dental implants into fresh extraction sites has become an acceptable treatment approach. However, immediate molar implant placement presents specific challenges because of the anatomical and physiologic limitations. Such implant surgeries commonly require procedures that use a barrier membrane to generate bone and soft tissue or one that seals the molar extraction socket through a coronally advanced flap. Here, as an alternative, we report a method for treating molar extraction socket wounds in the hard and soft tissues after immediate placement of an implant using a silicone sheet.
Imported Plasmodium vivax Malaria in the Russian Federation from Western Sub-Saharan Africa
Authors: Baranova Alla , Sergiev Vladimir , Morozova Lola , Turbabina Natalia , Morozov Evgeny
Published: February 2019

Background. Imported cases of Plasmodium vivax malaria from western Africa are reported annually in the Russian Federation. Infected native African people moving from western Africa for different purposes (students, businessmen, specialists, etc.) or Russian citizens (tourists, diplomats, businessmen, etc.) incubate the pathogen until reaching their Russian destination. Methods. All imported and other confirmed malaria cases and the associated Plasmodium species recorded over the past twenty years throughout the Russian Federation were inventoried. These data were included in the national register. The data of imported malaria cases were analysed according to the species of Plasmodium, case origin, dates of importation, and patient nationality. Results. A total of 267 P. vivax-infected patients who contracted the disease in western Africa were diagnosed in the Russian Federation from 1984 to 2017. Among them, 3 cases had mixed infections (2 with P. vivax + P. falciparum and 1 P. vivax + P. ovale). Conclusion. Our data reveal an existing risk of contracting P. vivax infections in towns of West sub-Saharan Africa despite the absence of local P. vivax infection records.
Stem Cell-Derived Extracellular Vesicles as Immunomodulatory Therapeutics
Authors: Seo Yoojin , Kim Hyung-Sik , Hong In-Sun
Published: February 2019

Mesenchymal stem cells (MSCs) have been reported to possess regulatory functions on immune cells which make them alternative therapeutics for the treatment of inflammatory and autoimmune diseases. The interaction between MSCs and immune cells through paracrine factors might be crucial for these immunomodulatory effects of MSCs. Extracellular vesicles (EVs) are defined as bilayer membrane structures including exosomes and microvesicles which contain bioactive paracrine molecules affecting the characteristics of target cells. Recently, several studies have revealed that EVs derived from MSCs (MSC-EVs) can reproduce similar therapeutic impacts of parent MSCs; MSC-EVs could regulate proliferation, maturation, polarization, and migration of various immune effector cells and modulate the immune microenvironment depending on the context by delivering inflammatory cytokines, transcription factors, and microRNAs. Therefore, MSC-EVs can be applied as novel and promising tools for the treatment of immune-related disorders to overcome the limitations of conventional cell therapy regarding efficacy and toxicity issues. In this review, we will discuss current insights regarding the major outcomes in the evaluation of MSC-EV function against inflammatory disease models, as well as immune cells.