bluuebunny/crossref_metadata_2025 huggingface dataset:
Can implementation failure or intervention failure explain the result of the 3D multimorbidity trial in general practice: mixed-methods process evaluation
Authors: Mann Cindy , Shaw Ali R G , Guthrie Bruce , Wye Lesley , Man Mei-See , Chaplin Katherine , Salisbury Chris
Published: November 2019

Objectives

During a cluster randomised trial, (the 3D study) of an intervention enacting recommended care for people with multimorbidity, including continuity of care and comprehensive biennial reviews, we examined implementation fidelity to interpret the trial outcome and inform future implementation decisions.

Design

Mixed-methods process evaluation using cross-trial data and a sample of practices, clinicians, administrators and patients. Interviews, focus groups and review observations were analysed thematically and integrated with quantitative data about implementation. Analysis was blind to trial outcomes and examined context, intervention adoption, reach and maintenance, and delivery of reviews to patients.

Setting

Thirty-three UK general practices in three areas.

Participants

The trial included 1546 people with multimorbidity. 11 general practitioners, 14 nurses, 7 administrators and 38 patients from 9 of 16 intervention practices were sampled for an interview.

Results

Staff loss, practice size and different administrative strategies influenced implementation fidelity. Practices with whole administrative team involvement and good alignment between the intervention and usual care generally implemented better. Fewer reviews than intended were delivered (49% of patients receiving both intended reviews, 30% partially reviewed). In completed reviews >90% of intended components were delivered, but review observations and interviews with patients and clinicians found variation in style of component delivery, from ‘tick-box’ to patient-centred approaches. Implementation barriers included inadequate skills training to implement patient-centred care planning, but patients reported increased patient-centredness due to comprehensive reviews, extra time and being asked about their health concerns.

Conclusions

Implementation failure contributed to lack of impact of the 3D intervention on the trial primary outcome (quality of life), but so did intervention failure since modifiable elements of intervention design were partially responsible. When a decisive distinction between implementation failure and intervention failure cannot be made, identifying potentially modifiable reasons for suboptimal implementation is important to enhance potential for impact and effectiveness of a redesigned intervention.

Trial registration number

ISRCTN06180958
Pharmacist-led adherence support in general practice: a qualitative interview study of adults with asthma
Authors: Mes Marissa Ayano , Katzer Caroline Brigitte , Wileman Vari , Chan Amy Hai Yan , Horne Robert , Taylor Stephanie Jane Caroline
Published: November 2019

Objectives

The National Health Service (NHS) in England recently introduced general practice pharmacists (GPPs) to provide medication-focused support to both patients and the general practice team. This healthcare model may benefit people with asthma, who currently receive suboptimal care and demonstrate low medication adherence. This study aimed to explore the perspectives of adults with asthma on the potential for pharmacist-led adherence support delivered in general practice, with a focus on how these perspectives are formed.

Design and setting

The study was conducted in the United Kingdom (UK) utilising a qualitative interview methodology. Participants were invited to partake in a telephone-based semistructured interview, followed by an online questionnaire for demographic details and asthma history. Qualitative data were analysed using thematic analysis.

Participants

Participants (n=17) were adults with asthma in the UK with a prescription for an inhaled corticosteroid. Participants did not have previous experience with GPPs and were asked to provide their views on a proposed GPP-led service.

Results

Participant perspectives of GPPs were determined by trust in pharmacists, perceived gaps in asthma care and the perceived strain on the NHS. Trust was based on pharmacists’ perceived clinical competency, established over time, and gauged through a ‘benchmarking’ process. GPP’s fit in current asthma care was assessed based on potential role overlap with other healthcare professionals, continuity of care and medication-related support needs. Participants navigated the NHS based on a perceived hierarchy of healthcare professionals (general practitioners on top, nurses, then pharmacists), and this influenced their perspectives of GPPs.

Conclusion

While the GPP scheme shows promise based on the perspectives of people with asthma, the identified barriers to optimal patient engagement and service implementation will need to be addressed for the service to be effective.
Evaluation of a 1-hour troponin algorithm for diagnosing myocardial infarction in high-risk patients admitted to a chest pain unit: the prospective FAST-MI cohort study
Authors: Amann Michael , Gaiser Felix , Schwenk Sandra Iris , Rahimi Faridun , Schmitz Roland , Mashayekhi Kambis , Ferenc Miroslaw , Neumann Franz-Josef , Valina Christian Marc , Hochholzer Willibald
Published: November 2019

Objective

This study sought to evaluate the diagnostic performance of the 1-hour troponin algorithm for diagnosis of myocardial infarction (MI) without persistent ST-segment elevations (non-ST-segment MI (NSTEMI)) in a cohort with a high prevalence of MI. This algorithm recommend by current guidelines was previously developed in cohorts with a prevalence of MI of less than 20%.

Design

Prospective cohort study from November 2015 until December 2016.

Setting

Dedicated chest pain unit of a single referral centre.

Participants

Consecutive patients with suspected MI were screened. Patients with subacute symptoms lasting more than 24 hours, new ST-segment elevations at presentation, or an already diagnosed or ruled-out acute MI were excluded. All enrolled patients (n=1317) underwent a full clinical assessment and measurements of high-sensitivity troponin, and were scheduled for an early invasive strategy if clinically indicated.

Main outcome measures

Final diagnosis of MI according to the Fourth Universal Definition of MI.

Results

The prevalence of NSTEMI in the present cohort was 36.9%. The sensitivity for rule-out of MI was 99.8%. The specificity for rule-in of MI was found to be 94.3%. However, in 35.7% of patients neither rule-in nor rule-out was possible. In 51.4% of patients diagnosed with MI, a primary non-coronary reason for MI was found (type 2 MI). Different receiver operating characteristic-curve derived cut-offs for troponin and its dynamics did not provide a sufficient differentiation between type 1 and 2 MI for clinical decision making (negative predictive value for rule-out of type 1 MI <70%).

Conclusions

The 1-hour diagnosis algorithm for patients with suspected NSTEMI can accurately diagnose acute MI in high-risk cohorts. However, discrimination between patients needing an early invasive strategy or not is limited.

Trial registration number

DRKS00009713.
Best emollients for eczema (BEE) – comparing four types of emollients in children with eczema: protocol for randomised trial and nested qualitative study
Authors: Ridd Matthew J , Wells Sian , Edwards Louisa , Santer Miriam , MacNeill Stephanie , Sanderson Emily , Sutton Eileen , Shaw Alison R G , Banks Jonathan , Garfield Kirsty , Roberts Amanda , Barrett Tiffany J , Baxter Helen , Taylor Jodi , Lane J Athene , Hay Alastair D , Williams Hywel C , Thomas Kim Suzanne
Published: November 2019

Introduction

Atopic dermatitis/eczema affects around 20% of children and is characterised by inflamed, dry, itchy skin. Guidelines recommend ‘leave-on’ emollients that are applied directly to the skin to add or trap moisture and used regularly, they can soothe, enhance the skin barrier and may prevent disease ‘flares’. However, the suitability of the many different emollients varies between people and there is little evidence to help prescribers and parents and carers decide which type to try first.

Methods and analysis

Design: pragmatic, multicentre, individually randomised, parallel group superiority trial of four types of emollient (lotions, creams, gel or ointments).

Setting: general practitioner surgeries in England.

Participants: children aged over 6 months and less than 12 years with mild-to-severe eczema and no known sensitivity to study emollients.

Interventions: study-approved lotion, cream, gel or ointment as the only leave-on emollient for 16 weeks, with directions to apply twice daily and as required. Other treatments, such as topical corticosteroids, used as standard care.

Follow-up: 52 weeks.

Primary outcome: validated patient-orientated eczema measure measured weekly for 16 weeks.

Secondary outcomes: eczema signs (Eczema Area Severity Index) by masked researcher, treatment use, parent satisfaction, adverse events, child and family quality of life (Atopic Dermatitis Quality of Life, Child Health Utility 9D and Dermatitis Family Impact).

Sample size: 520 participants (130 per group).

Analysis: intention-to-treat using linear mixed models for repeated measures.

Nested qualitative study: audio-recording of sample of baseline appointments and up to 60 interviews with participants at 4 and 16 weeks, interviews to be transcribed and analysed thematically.

Ethics and dissemination

Ethics approval granted by the NHS REC (South West - Central Bristol Research Ethics Committee 17/SW/0089). Findings will be presented at conferences, published in open-access peer-reviewed journals and the study website; and summaries shared with key stakeholders.

Trial registration number

ISRCTN84540529
Should we slaughter horses at abattoirs?
Authors: Owers Roly
Published: November 2019

Roly Owers argues that humanely slaughtering horses at abattoirs and entering them into the food chain could help to mitigate one of the key welfare challenges facing UK horses – delayed euthanasia.
Effect of canola (Brassica napus) cultivar rotation on Plasmodiophora brassicae pathotype composition
Authors: Cao Tiesen , Manolii Victor P. , Zhou Qixing , Hwang Sheau-Fang , Strelkov Stephen E.
Published: November 2019

In Canada, clubroot (Plasmodiophora brassicae) disease is managed mainly by planting clubroot resistant (CR) canola (Brassica napus). New pathotypes of P. brassicae have emerged recently, however, which are virulent on most CR canola cultivars. To understand the impact of cultivar rotation on pathotype abundance, greenhouse experiments were conducted in which different canola cultivar rotations were grown in a soil mix containing equal amounts of pathotypes 5X and 3, which are virulent and avirulent, respectively, on CR canola. The rotation treatments included: T1, the same susceptible cultivar planted over four cycles; T2, the same CR cultivar planted over four cycles; and T3, different CR cultivars planted in each cycle. Clubroot severity increased from cycles one to four in all treatments, with the exception of one CR cultivar in T3 that may carry a different source of resistance. Pathogen populations were recovered with a susceptible bait crop and pathotyped on the differentials of Williams plus a CR host (B. napus ‘Mendel’). The percentage of galls classified as pathotype 5X in T1 declined from 50% to 6.7% over the course of the experiment, while galls classified as pathotype 5X increased from 50% to 66.7% in both T2 and T3. Quantitative PCR analysis of the soil with pathotype 5X-specific primers generally confirmed an increase in 5X DNA. The results suggest that continuous planting of CR canola favours a rapid proliferation of virulent pathotypes of P. brassicae, as indicated by the increases in pathotype 5X observed in this study.
Seed coat anatomy ofCercis chinensisand its relationship to water uptake
Authors: Wang Huan , Chen Li , Dai Song , Ma Qiuyue , Wu Yang , Ma Qingjiang , Li Shuxian
Published: November 2019

The hard seed coat of Cercis chinensis Bunge is an important factor of its dormancy. A study of the characteristics of water absorption is vital for understanding seed dormancy and germination. This investigation found that soaking in water at an initial temperature of 80 °C for 5 min was optimal for breaking the hardness of C. chinensis seeds. Scanning electron microscopy (SEM), dye-tracking, and blocking experiments were used to examine the major water entry sites and the relationship between water uptake and seed coat structure during C. chinensis seed imbibition. The SEM images showed that the seed coat consisted of three layers: epidermis, palisade, and sclereid. Special light line, vascular bundle, and counter-palisade layer structures were found in the side of the hilum. The blocking experiments showed that the hilar region was an important water absorption site because, if the region was not blocked, it showed the highest water absorption when imbibed for 3–12 h. However, all parts of the seed coat can absorb water if enough time is allowed after the seed coat hardness has been broken. The dye-tracking test showed that after 3 h water entered the seed only via the hilum fissure. Therefore, the hilum fissure acts as the initial site of water absorption. When more time was allowed, water moved more rapidly on the side with vascular bundles than on the opposite side.
$$D=4$$ supergravity from the Maxwell-Weyl superalgebra
Authors: Kibaroğlu Salih , Cebecioğlu Oktay
Published: November 2019

We present the construction of the first-order $$D=4$$D=4, $${\mathcal {N}}=1$$N=1 supergravity action by gauging the Maxwell-Weyl superalgebra. The four-form lagrangian is constructed by using the curvatures of the algebra and the local scale invariance of the action is achieved through the introduction of a compensating scalar field. Finally, we find the generalized Einstein equation with a coordinate dependent cosmological term.
Heat generation/absorption and velocity slip effects on unsteady axisymmetric flow of Williamson magneto-nanofluid
Authors: Hamid Aamir , Hashim  , Khan Masood
Published: November 2019

Engineers and researchers in the field of heat transfer are in search of new techniques to optimize the performance of energy devices through heat transfer enhancement. For that reason, the flow analysis involving nanoparticles is assumed to be one of the most important techniques for enhancing heat transfer systems. Being a two-component system, different numerical approaches are available to model the thermo-fluids behavior of nanofluids. The current study describes the investigation of Buongiorno model for evaluation of transient flow and heat transfer of Williamson nanofluids under the impacts of velocity slip and magnetic field. In addition, the effects of heat generation/absorption and convective heat transfer have been employed in this analysis. The Boussinesq-approximations are implemented to obtain the governing conservation equations for nanofluids transport phenomenon. The leading equations of the modeled physical problem have been solved using a MATLAB code, based on Nachtsheim–Swigert shooting iteration scheme. The novelty of the current investigation is the existence of multiple solutions for the nanofluids flow past a radially shrinking surface by considering the effects of uniform suction at the wall. In this review, it is seen that the investigated physical parameters affect remarkably on the nanofluid stream function, temperature and nanoparticles concentration. The skin friction, local Nusselt number and the local Sherwood number and some samples of velocity, temperature and nanoparticle concentration profiles are discussed and presented with the help of graphs. From this study, it is observed that the existence range of dual solutions is significantly raised by the higher Weissenberg number.
Selective guest recognition by a metallo-organic phthalocyanine-based host
Authors: Fazio Ettore , Jesús Vicente-Arana M. , Teresa Alonso M. , Torres Tomás , de la Torre Gema
Published: November 2019

In this manuscript, we have studied the selectivity in the complexation of fullerene species by a Fe[Formula: see text]Pc[Formula: see text] metallo-organic helicate (1) assembled using a bidentate phthalocyanine (Pc) as ligand. The large aromatic internal surface of this helicate shows a strong selectivity towards the encapsulation of C[Formula: see text] from a mixture of C[Formula: see text] and C[Formula: see text]. On the other hand, a bisimidazole-containing naphthalenediimide was used to perform guest exchange experiments over [fullerene [Formula: see text] 1] complexes, taking advantage of the strong coordination bond of the imidazole ring to the Zn centers in the Pc cavity.
Random thinning model with a truncated credit quality vulnerability factor: Application to top-down-type credit risk assessment
Authors: Yamanaka Suguru
Published: November 2019

In the top-down approach of intensity-based credit risk modeling, a procedure called “random thinning” is needed to obtain credit event intensities for sub-portfolios. This paper presents a random thinning model incorporating a risk factor called the credit quality vulnerability factor (CQVF) to capture time-series variation in credit event occurrence in a target sub-portfolio. In particular, we propose a type of CQVF that follows truncated normal distributions specified by macroeconomic variables. Using credit event samples of Japanese firms, our empirical analysis aims to clarify the applicability and effectiveness of the proposed model to practical credit risk management. Since macroeconomic variables are included in our model, it is applicable to the macro-stress testing of portfolio credit risk management within a top-down-type framework.
Indicator mineral and till geochemical signatures of the Broken Hammer Cu–Ni–PGE–Au deposit, North Range, Sudbury Structure, Ontario, Canada
Authors: McClenaghan M. B. , Ames D. E. , Cabri L. J.
Published: November 2019

The Broken Hammer Cu–Ni–PGE–Au footwall deposit in the North Range of the Sudbury Structure in Canada consists of a shallow surface zone of vein-hosted and vein stockwork-hosted mineralization within Sudbury breccia developed in the quartz monzonite Levack Gneiss Complex. The surface of the deposit consists of a 2–120 cm wide chalcopyrite vein and numerous smaller veins dominated by chalcopyrite–magnetite–millerite with trace gold, platinum group minerals, tellurides, bismuthides and selenides. The Laurentide Ice Sheet flowed southward across the region depositing a sandy till that contains abundant sperrylite (hundreds of grains), chalcopyrite, pyrite and gold in the heavy mineral fraction down-ice of mineralization. Mineral liberation analysis of the <0.25 mm heavy mineral fraction of metal-rich till identified a broader suite of PGM and sulfides than visual identification methods. The <0.063 mm fraction of till displays a strong geochemical signature of the mineralization for Pd, Pt, Au, Cu and Ag and, to a lesser extent, Bi, Te and Sn; however, geochemical signatures are not detectable as far down-ice as indicator minerals. Till sampling has not been used for exploration in the Sudbury region because of the abundant outcrop and the use of geophysical and prospecting techniques. This study demonstrates that indicator mineral and till geochemical methods are useful exploration tools for the region. The presence of sperrylite and chalcopyrite in oxidized till indicates that even thin (<1 m) highly weathered till is an effective sample medium here.
Enhancing the Therapeutic Efficacy of Daunorubicin and Mitoxantrone with Bavachinin, Candidone, and Tephrosin
Authors: Darzi Sina , Mirzaei Seyed Abbas , Elahian Fatemeh , Shirian Sadegh , Peymani Amir , Rahmani Babak , Dibazar Shaghayegh Pishkhan , Aali Ehsan
Published: November 2019

The capability of flavonoids in sensitizing cancer cells was demonstrated in numerous works to chemotherapy and converse multidrug resistance by modulating efflux pumps and apoptosis mechanisms. Three flavonoids, namely, bavachinin, tephrosin, and candidone, have been recently introduced to cancer treatment research presenting various activities, such as antibacterial, immunomodulatory, cell death, and anticancer. Less information exists regarding the therapeutic significance of these flavonoids in cancer treatment, especially in overcoming multidrug resistance (MDR). Here, we tempted to investigate the potency of these agents in reversing MDR by analyzing their effects as chemosensitizers on cell cytotoxicity, P-gp and ABCG2 protein expression levels, and their function on two multidrug-resistant cell lines, P-gp-overexpressing human gastric adenocarcinoma cell line (EPG85.257RDB) and ABCG2-overexpressing human epithelial breast cancer cell line (MCF7/MX). The inhibitory concentration of 10% (IC10) of bavachinin, tephrosin, and candidone in EPG85.257RDB cells was 1588.7 ± 202.2, 264.8 ± 86.15, and 1338.6 ± 114.11 nM, respectively. Moreover, these values in MCF7/MX cell were 2406.4 ± 257.63, 38.8 ± 4.28, and 27.9 ± 5.59 nM, respectively. Expression levels of ABCG2 and P-gp were not significantly downregulated by these flavonoids. Maximum levels of daunorubicin and mitoxantrone accumulations and minimum rates of drug efflux in both cell lines were detected 48 hrs posttreatment with tephrosin and bavachinin, respectively. Chemosensitization to mitoxantrone and daunorubicin treatments was, respectively, achieved in MCF7/MX and EPG85.257RDB cells in response to IC10 of bavachinin and tephrosin, independently. These effects did not follow time-dependent manner, and each flavonoid had its cell-dependent patterns. Overall, bavachinin, tephrosin, and candidone showed potency to sensitize MDR cells to daunorubicin and mitoxantrone and could be considered as attractive MDR modulators for cancer treatment. However, their action was time and cell specific.
Type 2 Diabetes Mellitus Increases the Risk to Hip Fracture in Postmenopausal Osteoporosis by Deteriorating the Trabecular Bone Microarchitecture and Bone Mass
Authors: Mohsin Sahar , Kaimala Suneesh , Sunny Jens Jolly , Adeghate Ernest , Brown Eric Mensah
Published: November 2019

T2DM is linked to an increase in the fracture rate as compared to the nondiabetic population even with normal or raised bone mineral density (BMD). Hence, bone quality plays an important role in the pathogenesis of skeletal fragility due to T2DM. This study analyzed the changes in the trabecular bone microstructure due to T2DM at various time points in ovariectomized and nonovariectomized rats. Animals were divided into four groups: (I) control (sham), (II) diabetic (sham), (III) ovariectomized, and (IV) ovariectomized with diabetes. The trabecular microarchitecture of the femoral head was characterized using a micro-CT. The differences between the groups were analyzed at 8, 10, and 14 weeks of the onset of T2DM using a two-way analysis of variance and by post hoc multiple comparisons. The diabetic group with and without ovariectomies demonstrated a significant increase in trabecular separation and a decrease in bone volume fraction, trabecular number, and thickness. BMD decreased in ovariectomized diabetic animals at 14 weeks of the onset of T2DM. No significant change was found in connectivity density and degree of anisotropy among groups. The structural model index suggested a change towards a weaker rod-like microstructure in diabetic animals. The data obtained suggested that T2DM affects the trabecular structure within a rat’s femoral heads negatively and changes are most significant at a longer duration of T2DM, increasing the risk to hip fractures.
Discrete Element Analysis for Hydraulic Fracture Propagations in Laminated Reservoirs with Complex Initial Joint Properties
Authors: Dou Fakai , Wang J. G. , Wang Huimin , Hu Bowen , Li Chengxuan
Published: November 2019

Previous studies on hydraulic fracturing mainly focus on the effects of the in-situ stress state, permeability, fracturing fluids, and approach angle in homogeneous rocks, but the impacts of joint mechanical properties in laminated shale reservoirs on the propagation and formation of the fracture network are still unclear. In this study, a coupled fluid-mechanical model was developed to investigate the impacts of joint mechanical properties on hydraulic fracture propagation. Then, this model was validated with Blanton’s criterion and some experimental observations on fracture morphology. Finally, a series of numerical simulations were conducted to comparatively analyze the impacts of joint mechanical properties on the total crack number, the percentage and distribution of each fracture type, the process of crack propagation, and the final fracture morphology. Numerical results show that the cracking behaviors induced by joint mechanical properties vary with the approach angle. Joint strength has a significant influence on the generation of matrix tensile cracks. The tensile-to-shear strength ratio plays an even more important role in the shear slips of bedding planes and is conducive to the formation of complex fracture morphology.
In a Rat Model of Acute Liver Failure, Icaritin Improved the Therapeutic Effect of Mesenchymal Stem Cells by Activation of the Hepatocyte Growth Factor/c-Met Pathway
Authors: Wang Lu , Li Shu , Wang Han-Yu , Zeng Juan , Zhang Zheng-Zheng , Lv Dong-Yong , Kuang Wei-Hong
Published: November 2019

Acute liver failure (ALF) is a serious life-threatening condition. Mesenchymal stem cells (MSCs) may be an effective treatment for this condition and a good alternative to liver transplantation. Icaritin (ICT) is an active ingredient of the genus Epimedium, a traditional Chinese medicine, with the potential to enhance the proliferation of MSCs. The purpose of this study was to explore whether ICT increased the therapeutic effects of MSCs and explore its underlying mechanisms. For in vivo experiments, a rat ALF model was established by intraperitoneal injection of D(+)-galactosamine/ lipopolysaccharide. MSCs cocultured with ICT were used to treat ALF rats and the protective effects assessed as survival rate, levels of serum AST and ALT, and histological changes in liver tissue. For in vitro experiments, MSCs were treated in serum-free culture for 72 h to simulate the disruption of intrahepatic microcirculation. MSCs apoptosis was examined to determine whether ICT rescued impaired MSCs. The role of the hepatocyte growth factor (HGF)/c-Met pathway in MSCs was assessed by constructing genetically modified MSCs overexpressing c-Met and by using the c-Met receptor inhibitor (crizotinib). The results showed that MSCs increased the survival rate of ALF rats and reduced liver damage. MSCs cocultured with ICT exerted a greater therapeutic effect than MSCs alone. Further, the HGF/c-Met pathway played a key role in the antiapoptotic activity of MSCs, which was associated with the optimized efficacy of ICT. In conclusion, this study demonstrated that ICT enhances the therapeutic effect of MSCs in a model of ALF, improving the antiapoptotic potential of MSCs by upregulation of the HGF/c-Met pathway. The combination of stem cell therapy with traditional herbal extracts may improve MSC-based clinical applications.
Serum-Free Culture of Human Mesenchymal Stem Cell Aggregates in Suspension Bioreactors for Tissue Engineering Applications
Authors: Allen Leah M. , Matyas John , Ungrin Mark , Hart David A. , Sen Arindom
Published: November 2019

Mesenchymal stem cells (MSCs) have the capacity to differentiate towards bone, fat, and cartilage lineages. The most widely used culture and differentiation protocols for MSCs are currently limited by their use of serum-containing media and small-scale static culture vessels. Suspension bioreactors have multiple advantages over static culture vessels (e.g., scalability, control, and mechanical forces). This study sought to compare the formation and culture of 3D aggregates of human synovial fluid MSCs within suspension bioreactors and static microwell plates. It also sought to elucidate the benefits of these techniques in terms of productivity, cell number, and ability to generate aggregates containing extracellular matrix deposition. MSCs in serum-free medium were either (1) inoculated as single cells into suspension bioreactors, (2) aggregated using static microwell plates prior to being inoculated in the bioreactor environment, or (3) aggregated using microwell plates and kept in the static environment. Preformed aggregates that were size-controlled at inoculation had a greater tendency to form large, irregular super aggregates after a few days of suspension culture. The single MSCs inoculated into suspension bioreactors formed a more uniform population of smaller aggregates after a definite culture period of 8 days. Both techniques showed initial deposition of extracellular matrix within the aggregates. When the relationship between aggregate size and ECM deposition was investigated in static culture, midsized aggregates (100-300 cells/aggregate) were found to most consistently maximize sGAG and collagen productivity. Thus, this study presents a 3D tissue culture method, which avoids the clinical drawbacks of serum-containing medium that can easily be scaled for tissue culture applications.
A Coupling Dynamics Analysis Method for Two‐Stage Spur Gear under Multisource Time‐Varying Excitation
Authors: Qiao Zizhen , Zhou Jianxing , Sun Wenlei , Zhang Xiangfeng
Published: November 2019

A new modeling method is proposed to simulate the dynamic response of a two‐stage gear transmission system using the finite element method (FEM). The continuous system is divided into four modules: shaft‐shaft element, shaft‐gear element, shaft‐bearing element, and gear‐gear element. According to the FEM, the model is built with each element assembled. Meanwhile, the model considers the time‐varying mesh stiffness (TVMS), bearing time‐varying stiffness (BTVS), and the shaft flexibility. The Newmark integration method (NIM) is used to obtain the dynamic response of the spur gear system. Results show that vibration amplitude and the number of frequency components decrease after considering shaft flexibility through comparing the gear dynamic response under the condition of flexible shaft and rigid shaft. When the effect of bearing stiffness is considered, there will be a bearing passing frequency component in the frequency spectrum. In addition, the result shows that the simulation and experimental test of the frequency component are basically consistent. Furthermore, the theoretical model is validated against an experimental platform of the two‐stage gear transmission system and the dynamic responses are compared under the condition of increasing speed. Additionally, the increase of shaft stiffness not only changes some of the dominant mode shapes (torsional mode shapes) but also makes the number of primary resonance speeds added. The method can be used to guide the design of gear systems.
Minimization of Ground Vibration Test Configurations for F‐16 Aircraft by Subtractive Modification
Authors: Koksal Sertac , Yildiz Erdinc Nuri , Yazicioglu Yigit , Ozgen Gokhan Osman
Published: November 2019

The certification process of external loads designed for aircraft needs to satisfy various criteria where compatibility with existing systems is one of the essential requirements. Flight flutter testing is a critical part of a certification process that requires many preliminary studies. Computational flutter analysis must precede actual flutter test to determine an approximately safe flight envelope to ensure the safety of the personnel and aircraft. To be able to perform flutter analysis of an aircraft, an accurate structural model such as finite element (FE) model is required. An accurate FE model can be obtained from a coarse model using ground vibration test (GVT) which is also the primary test campaign for certification of a new external load, new aircraft design, or modification on existing aircraft. On the other hand, performing GVT for each configuration of an aircraft is both time consuming and costly. It would be more practical to determine the critical configurations for an aircraft using computational tools and perform actual GVT for those configurations. The objective of this study is to simulate GVT characteristics for downloading and fuel configurations of F‐16 aircraft. A novel methodology is proposed where various loading configurations can be simulated by subtractive modification from loaded GVT data so that joint stiffnesses between stores and aircraft need not be identified. The proposed technique decreases the number of necessary physical GVT testing campaigns.
Efficacy and Tolerability of Topical Polyphenon E in Multiple “Seborrheic Keratosis-Like” Lesions of the Groin in an Immunocompetent 26-Year-Old Man
Authors: Pizzini Luigi , De Luca Graziano , Milani Massimo
Published: November 2019

Polyphenon E 10%, a green tea extract containing epigallocatechin gallate (EGCG) as the main active compound, is a topical formulation indicated for the treatment of genital warts. Polyphenon E has also shown to be very effective in the treatment of periungual and plane warts. Here, we report a dramatic clinical effect of topical treatment with polyphenon E in a subject with multiple “seborrheic keratosis-like” lesions of the genital area. An immunocompetent 26-year-old Caucasian man came to our attention in October 2018. The subject, a regular blood donor, presented several (more than 100) light brown dome-shaped papular lesions in the groin area and in the penile shaft. A clinical diagnosis of Bowenoid papulosis-like multiple condylomata of the groin was made. A 2-month imiquimod treatment did not induce any relevant improvement in terms of volume and number of lesions. A treatment with Polyphenon E, a topical green tea extract with 10% of EGCG (Veregen®), was therefore started. After 2 months of Polyphenon E treatment, a dramatic reduction of the majority of the lesions was observed. After 3 months of treatment, all the lesions disappeared with only hyperchromic residues. Histological and immunohistological findings supported seborrheic keratosis as the conclusive diagnosis. This case report suggests that topical green tea extract could be very effective in the treatment of “seborrheic keratosis-like” lesions of the inguinal area.
Alinhamento de Capacidades Colaborativas para Sustentabilidade por meio do Analytic Hierarchy Process
Authors: Moura Nathalia Rodarte de , Gohr Cláudia Fabiana , Nóbrega Bruna Medeiros da , Gonçalves Juliana
Published: November 2019

O desenvolvimento de Capacidades Colaborativas para Sustentabilidade (CCS) por parte das empresas é uma prática fundamental para a permanência duradoura no mercado. No entanto, a literatura sobre CCS ainda é escassa, principalmente quando se considera a avaliação desta por meio de modelagem matemática. Este artigo tem como principal objetivo analisar quantitativamente a CCS de um hotel que atua no cluster de turismo no estado da Paraíba. Para isso, foram levados em consideração aspectos da visão relacional, da visão baseada em recursos naturais e de capacidades colaborativas, bem como foi utilizada a ferramenta multicritério Analytic Hierarchy Process (AHP). Como resultado, verificou-se que os atributos de CCS que devem ser melhorados para ampliar o potencial de colaborar para a sustentabilidade do hotel avaliado são: alocação de recursos e gestão da cadeia de valor. Dentre as contribuições do artigo, destacam-se o avanço do conhecimento sobre a temática ainda não explorada na literatura e a avaliação quantitativa da CCS por meio de uma ferramenta multicritério.
Reasons for the Failure of Platelet Function Testing to Adjust Antiplatelet Therapy
Authors: Lattuca Benoit , Silvain Johanne , Yan Yan , Pouillot Christophe , Cuisset Thomas , Cayla Guillaume , Henry Patrick , Diallo Abdourahmane , Elhadad Simon , Rangé Grégoire , Lhermusier Thibault , Boueri Ziad , Motreff Pascal , Carrié Didier , Vicaut Eric , Montalescot Gilles , Collet Jean-Philippe
Published: November 2019

Background:

In the ARCTIC trial (Assessment by a Double Randomization of a Conventional Antiplatelet Strategy Versus a Monitoring-Guided Strategy for Drug-Eluting Stent Implantation and of Treatment Interruption Versus Continuation One Year After Stenting), treatment adjustment following platelet function testing failed to improve clinical outcomes. However, high-on-treatment platelet reactivity (HPR) is considered as a predictor of poor ischemic outcome. This prespecified substudy evaluated clinical outcomes according to the residual platelet reactivity status after antiplatelet therapy adjustment.

Methods:

We analyzed the 1213 patients assigned to the monitoring arm of the ARCTIC trial in whom platelet reactivity was evaluated by the VerifyNow P2Y
12
test before percutaneous coronary intervention and during the maintenance phase (at 14 days). HPR was defined as platelet reaction unit≥235U. The primary ischemic end point, a composite of death, myocardial infarction, stent thrombosis, stroke, or urgent revascularization and the safety end point of major bleeding were assessed according to the platelet reactivity status.

Results:

Before percutaneous coronary intervention, 35.7% of patients displayed HPR (n=419). During the acute phase, between percutaneous coronary intervention and the 14-day platelet function testing, ischemic (adjusted hazard ratio, 0.94 [95% CI, 0.74–1.18];
P
=0.58) and safety outcomes (hazard ratio, 1.28 [95% CI, 0.22–7.59];
P
=0.78) were similar in HPR and non-HPR patients. During the maintenance phase, the proportion of HPR patients (n=186, 17.4%) decreased by 56%. At 1-year, there was no difference for the ischemic end point (5.9% versus 6.0%; adjusted hazard ratio, 0.79 [95% CI, 0.40–1.58];
P
=0.51) and a nonsignificant higher rate of major bleedings (2.7% versus 1.0%, hazard ratio, 2.83 [95% CI, 0.96–8.41];
P
=0.06) in HPR versus non-HPR patients.

Conclusions:

The proportion of HPR was halved after platelet function testing and treatment adjustment but without significant ischemic benefit at 1 year. HPR seems more as a modifiable risk marker than a risk factor of ischemic outcome.

Clinical Trial Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT00827411.
Can Signal Delay be Functional? Including Delay in Evolved Robot Controllers
Authors: Egbert Matthew , Keane Andrew , Postlethwaite Claire , Wong Nelson
Published: November 2019

Engineers, control theorists, and neuroscientists often view the delay imposed by finite signal propagation velocities as a problem that needs to be compensated for or avoided. In this article, we consider the alternative possibility that in some cases, signal delay can be used functionally, that is, as an essential component of a cognitive system. To investigate this idea, we evolve a minimal robot controller to solve a basic stimulus-distinction task. The controller is constrained so that the solution must utilize a delayed recurrent signal. Different from previous evolutionary robotics studies, our controller is modeled using delay differential equations, which (unlike the ordinary differential equations of conventional continuous-time recurrent neural networks) can accurately capture delays in signal propagation. We analyze the evolved controller and its interaction with its environment using classical dynamical systems techniques. The analysis shows what kinds of invariant sets underlie the various successful and unsuccessful performances of the robot, and what kinds of bifurcations produce these invariant sets. In the second phase of our analysis, we turn our attention to the parameter θ, which describes the amount of signal delay included in the model. We show how the delay destabilizes certain attractors that would exist if there were no delay and creates other stable attractors, resulting in an agent that performs well at the target task.
Reinforcement Learning for Improving Agent Design
Authors: Ha David
Published: November 2019

In many reinforcement learning tasks, the goal is to learn a policy to manipulate an agent, whose design is fixed, to maximize some notion of cumulative reward. The design of the agent's physical structure is rarely optimized for the task at hand. In this work, we explore the possibility of learning a version of the agent's design that is better suited for its task, jointly with the policy. We propose an alteration to the popular OpenAI Gym framework, where we parameterize parts of an environment, and allow an agent to jointly learn to modify these environment parameters along with its policy. We demonstrate that an agent can learn a better structure of its body that is not only better suited for the task, but also facilitates policy learning. Joint learning of policy and structure may even uncover design principles that are useful for assisted-design applications.
The Tension between the Presumption of Innocence and Victims’ Participation Rights at the International Criminal Court
Authors: Coleman Michelle
Published: November 2019

This article explores where participation rights of victims and the presumption of innocence come into conflict within the context of the International Criminal Court (icc) and whether this causes either set of rights to be violated. First it discusses the development of the right to the presumption of innocence at the icc and explains victims’ participation rights. Next it outlines how conflict between these two rights should be resolved. The article then examines three areas in which there is tension between victims’ participation and the presumption of innocence. These areas are: calling victims ‘victims’; evidence submission; and participation by questioning witnesses. Finally, the article concludes that the rights of victims and the accused can come into conflict and that in order to ensure that the right to the presumption of innocence is protected, and to provide victims with a meaningful right to participation, victims’ rights must be more clearly defined.
Revision of Australian species of the dung beetle genus Lepanus (Coleoptera: Scarabaeidae: Scarabaeinae): description of 10 new species from the L. australis, L. monteithi, and L. villosus species groups
Authors: GUNTER NICOLE L. , WEIR THOMAS A.
Published: November 2019

This publication is part in an ongoing revision of the Australian species of the genus Lepanus Balthasar, 1966 (Coleoptera: Scarabaeidae: Scarabaeinae) and revises the three species groups with simple pygidia. Keys to species within the L. australis Matthews, 1974, L. monteithi Matthews, 1974, and L. villosus Matthews, 1974 species groups are provided and a total of 10 new species are described. Within the L. australis species group, L. australis Matthews, 1974 and L. latheticus Matthews, 1974 are redescribed and four new species are described: Lepanus burnetti new species and Lepanus oxleyi new species from southeastern Queensland; Lepanus eungella new species from coastal, central Queensland; and Lepanus dukungarri new species from Australian Wet Tropics, northern Queensland. Within the L. monteithi species group, L. monteithi Matthews, 1974 is redescribed and four new species are described: Lepanus geoffi new species from Cape York Peninsula, far north Queensland; Lepanus yorkensis new species from Torres Strait and Cape York Peninsula, far north Queensland; Lepanus reidi new species from the Australian Wet Tropics and Lepanus topend new species from the northern Northern Territory. Within the L. villosus species group, L. villosus Matthews, 1974 and L. vestitus Matthews, 1974 are redescribed and two new species are described: Lepanus pseudovillosus new species and Lepanus reticulatus new species from the Australian Wet Tropics, northern Queensland. Including these descriptions a total of 43 Lepanus species are now described from Australia.
Thrombin Induces Cerebral Vasospasm Effect via Proteinase-Activated Receptor-1 (PAR-1)/Tumor Necrosis Factor-α (TNF-α) Inflammatory Pathways in Subarachnoid Hemorrhage Rat Model
Authors: Li Gang , Wang Qingsong , Lin Tingting , Liu Chengye
Published: November 2019

To study thrombin (TM) damage effect and detailed quantitative relation on cerebral vessels function, and to explore inflammatory mechanism of TM on cerebral vasospasm (CVS) in vivo. Wild type SD rats were randomly assigned into different groups for further experiments. Subarachnoid
hemorrhage (SAH) rat model was established with double injections of the autogenous blood into the cisterna magna. TM injection was performed during the first injection of the autogenous blood. Primary groups were control group, SAH group TM group and TM+SAH group. In addition, TM+SAH group
contains several groups with different injection doses or TM intervention duration. HE staining was performed to detect injury of cerebral basilar artery. Histopathologic examination was performed to detect intra-lumen area of cerebral basilar artery. Each specimen was to be detected the expressive
level of Proteinase-activated Receptor-1 (PAR-1) and Tumor necrosis factor-α (TNF-α) by immunohistochemistry. The mean optical density (MOD) values of PAR-1 and TNF-α were used as the semiquantitative indicators to conduct statistical analysis. Compared
with the control group, the rat basilar artery intra-lumen area of TM group and TM+SAH group were significantly smaller (P < 0.05), while MOD value of PAR-1 and TNF-α of basilar artery were higher (P < 0.05). With equal dose of TM, the basilar artery intra-lumen
area of TM+SAH group are larger than SAH group (P < 0.05), suggesting TM exacerbated SAH injury. Among TM+SAM sub-groups, with the TM concentration increased, the basilar artery intra-lumen area became smaller, and the MOD value of PAR-1 and TNF-α of basilar artery gradually
increased, suggesting CVS effect of TM was dose-dependent. Meanwhile, CVS effect of TM was also time-dependent, verified by comparisons of sub-groups with different TM intervention duration (P < 0.05). Thrombin induces CVS effect to aggravate SAH injury via PAR-1/TNF-α
inflammatory pathways. Such pathological role of TM was both dose-dependent and time-dependent.
Combinatorial Therapeutic Drug Delivery of Riboflavin and Olopetadine for the Treatment of Keratoconus Affected Corneas of Mice
Authors: Yang Geqiang , Xue Yushun , Zhu Yanni , Qin Ying , Zhang Jing
Published: November 2019

The present study deals with the development and evaluation of novel thermoreversible gel containing Riboflavin and Olopatadine for the treatment of Keratoconus. The novel gel was prepared by using polymers like Poloxamer and hydroxypropyl methyl cellulose (HPMC) using cold method.
The formulated system was evaluated for clarity, appearance, pH, gelling temperature, ex vivo diffusion study, Isotonicity, hemolytic study and effect in keratoconus affected mice model. The results showed that formulated gel was found to be clear and transparent having high gelling
capacity. The pH was found between 6.5 to 6.9 and gelation temperature between 34 to 37 °C. All formulations were found isotonic and the hemolytic study performed proved the non-hemolytic nature of formulation. Drug content was also within acceptable limit. The F5 formulation was found
to be optimized considering all evaluation parameters. F5 formulation showed maximum amount of release (98.5 and 99.6% for Ribo and Olo respectively) within 8 hrs as compare to other formulations. The effect of formulation on keratoconus affected mice showed that matrix can be produced after
stimulation of KC cells and the increased thickness can be result of increase number of cells or matrix produced per cell. These results clearly conclude the potential of combinatorial therapeutic drug delivery of riboflavin and olopetadine for the treatment of keratoconus affected corneas
of mice.