bluuebunny/crossref_metadata_2025 huggingface dataset:
Computational Optimization Study of Transcatheter Aortic Valve Leaflet Design Using Porcine and Bovine Leaflets
Authors: Travaglino Stefano , Murdock Kyle , Tran Anh , Martin Caitlin , Liang Liang , Wang Yan , Sun Wei
Published: July 2019

In this study, a Bayesian optimization (BO) based computational framework is developed to investigate the design of transcatheter aortic valve (TAV) leaflets and to optimize leaflet geometry such that its peak stress under the blood pressure of 120 mmHg is reduced. A generic TAV model is parametrized by mathematical equations describing its 2D shape and its 3D stent-leaflet assembly line. Material properties previously obtained for bovine pericardium (BP) and porcine pericardium (PP) via a combination of flexural and biaxial tensile testing were incorporated into the finite element (FE) model of TAV. A BO approach was employed to investigate about 1000 leaflet designs for each material under the nominal circular deployment and physiological loading conditions. The optimal parameter values of the TAV model were obtained, corresponding to leaflet shapes that can reduce the peak stress by 16.7% in BP and 18.0% in PP, compared with that from the initial generic TAV model. Furthermore, it was observed that while peak stresses tend to concentrate near the stent-leaflet attachment edge, optimized geometries benefit from more uniform stress distributions in the leaflet circumferential direction. Our analysis also showed that increasing leaflet contact area redistributes peak stresses to the belly region contributing to peak stress reduction. The results from this study may inspire new TAV designs that can have better durability.
Phase Diagram of Pinch-off Behaviors During Drop-on-Demand Inkjetting of Alginate Solutions
Authors: Xu Changxue , Zhang Zhengyi , Huang Yong , Xu Heqi
Published: July 2019

Viscoelastic polymer solutions have been extensively utilized in inkjet printing for a variety of biomedical applications. The pinch-off of viscoelastic jets is a key step toward the generation of droplets in inkjet printing. This complex process is governed by the interplay of four stresses, including inertial stress, capillary stress, viscous stress, and elastic stress. Depending on polymer solution properties and process conditions, four types of pinch-off phenomenon were observed during inkjetting of viscoelastic alginate solutions. In this study, material properties of alginate solutions with different concentrations have been characterized, and three dimensionless numbers (Ohnesorge number Oh, Deborah number De, and Weber number We) have been proposed to analyze different pinch-off behaviors. The phase diagram in terms of these three dimensionless numbers has been constructed to classify the regimes for different pinch-off types during inkjetting of viscoelastic alginate solutions. It is found that (1) at low De and Oh, the capillary stress is mainly balanced by the inertial stress, resulting in front pinching. (2) At medium De and low Oh, with the increase of We, the pinch-off type may change from front pinching to hybrid pinching to exit pinching. (3) At low Oh and high De, the capillary stress is mainly balanced by the elastic stress, resulting in exit pinching. (4) At high Oh and De, the viscoelastic effect is dominant. With the increase of We, middle pinching turns to be exit pinching due to the increase in the initial ligament diameter near the forming droplet.
Evaluation of Electrode Degradation and Projection Weld Strength in the Joining of Steel Nuts to Galvanized Advanced High Strength Steel
Authors: Enrique Pablo D. , Al Momani Hashem , DiGiovanni Christopher , Jiao Zhen , Chan Kevin R. , Zhou Norman Y.
Published: July 2019

Projection welding of steel weld nuts to advanced high strength steel (AHSS) in automotive applications allows for the reliable mounting of critical components with different thicknesses to the vehicle body. However, the galvanized coatings commonly used on AHSS result in electrode surface degradation during welding. In this study, the electrode degradation and its effect on the mechanical properties of welded steel nuts and AHSS sheets are investigated. Two common electrode materials are tungsten/copper and beryllium-free class III copper—both display the formation of an oxidized alloy surface layer and pitting as weld number increases. Unlike resistance spot welding, where electrodes grow in the contact area diameter as they degrade, projection welding electrodes do not experience this type of mechanical degradation. Instead, increased resistance at the electrode interface with increasing weld number results in higher temperatures at the weld interface and a larger fusion zone size, which is responsible for an observed 30% increase in weld strength over the span of 10,000 welds.
Transferring Design Strategies From Human to Computer and Across Design Problems
Authors: Raina Ayush , Cagan Jonathan , McComb Christopher
Published: July 2019

Solving any design problem involves planning and strategizing, where intermediate processes are identified and then sequenced. This is an abstract skill that designers learn over time and then use across similar problems. However, this transfer of strategies in design has not been effectively modeled or leveraged within computational agents. This note presents an approach to represent design strategies using a probabilistic model. The model provides a mechanism to generate new designs based on certain design strategies while solving configuration design task in a sequential manner. This work also demonstrates that this probabilistic representation can be used to transfer strategies from human designers to computational design agents in a way that is general and useful. This transfer-driven approach opens up the possibility of identifying high-performing behavior in human designers and using it to guide computational design agents. Finally, a quintessential behavior of transfer learning is illustrated by agents as transferring design strategies across different problems led to an improvement in agent performance. The work presented in this study leverages the Cognitively Inspired Simulated Annealing Teams (CISAT) framework, an agent-based model that has been shown to mimic human problem-solving in configuration design problems.
Application of Wireless Technologies in a Nuclear Plant: Evaluation of Electromagnetic Propagation With Different Computational Techniques
Authors: Cappelli Mauro , Lopresto Vanni , Cecchi Riccardo , Marrocco Gaetano
Published: July 2019

The aim of this work is to present a preliminary investigation on the propagation of electromagnetic fields generated by wireless technologies inside a nuclear facility or power plant. First, a survey of currently proposed wireless technologies for nuclear facilities and plants has been carried out. Then, for selected scenarios, the electromagnetic field propagation has been studied by means of electromagnetic simulation tools, and the presence of the nuclear environment has been simulated by properly modeling environmental parameters and engineered barriers. The choice of the proper simulation techniques and tools is mandatory in order to simulate the effect of the realistic environment on the propagation. Accordingly, the feasibility of wireless technologies application at nuclear facilities can be assessed on the basis of results achieved from simulated scenarios. The goal is to analyze, for selected scenarios, possible issues due to the propagation of an electromagnetic field in the presence of simplified barriers mimicking the real nuclear environment. This approach can provide indications on how to deploy potential benefits of wireless technologies in a nuclear environment, evaluating pros and cons of the investigated technologies.
Dynamic Load Balancing Using Actual Workload Traces Based on Central Processing Unit Temperatures
Authors: Nakajo Yusuke , Athavale Jayati , Yoda Minami , Joshi Yogendra , Nishi Hiroaki
Published: July 2019

With the rapid growth in demand for distributed computing, data centers are a critical physical component of the “cloud.” Recent studies show that the energy consumption of data centers for both cooling and computing keeps increasing, and the growth in server power densities makes it ever more challenging to keep the servers below their maximum operating temperature. This paper presents a new dynamic load-balancing approach based on individual server central processing unit (CPU) temperatures. In this approach, a load balancer assigns a task in real time to a server based on the objective to keep the CPU temperatures below a maximum value. Experimental studies are conducted in a single rack based on production workload traces of Google clusters. This study also compares the performance of this method with two other load balancing approaches, Round Robin, and a CPU utilization-based method in terms of temperature distributions, local fan rotation speeds, system loads, and server processing times. Furthermore, we investigate how the effect of the proposed load balancing changes with different assumed applications run on servers. The results indicate that this new method can more effectively reduce both server CPU temperatures and local fan rotation speed in a rack especially for the most of web applications.
Effect of Ni and Zn Elements on the Microstructure and Antibacterial Properties of Cu Coatings
Authors: Al-Athel Khaled S. , Marraiki Najat , Arif Abul Fazal M. , Akhtar Syed Sohail , Mostaghimi Javad , Ibrahim Mohamed
Published: July 2019

In this work, 316L stainless steel samples were coated with copper (Cu) and German silver (Cu 17%Ni 10%Zn) to investigate the relation between their mechanical and antibacterial behaviors. The mechanical and material characteristics of the samples were studied by looking into the microstructure of the surface and the cross-section of the coatings, the surface roughness, and the adhesion strength between the coating layer and the substrate. The antibacterial behavior is then studied against gram-negative Escherichia coli and gram-positive Staphylococcus aureus. Two experiments were conducted to examine the antibacterial behavior. In the first experiment, the coated samples were covered with distilled water, whereas in the second experiment, the samples were tested without being covered with distilled water. The results show that German silver (Cu 17%Ni 10%Zn) had a higher antibacterial rate than copper (Cu) by around 10% for both gram-negative E. coli and gram-positive S. aureus. The reason is because a smoother surface is expected to limit the bacterial adhesion in most cases, and the German silver samples have a lower surface roughness (Ra) due to the higher thermal expansion value of zinc (Zn) compared with copper (Cu). A more in-depth look into the effect of various thickness of the coating with alloying elements (in this case nickel and zinc) on the antibacterial rate would be of great interest.
A Novel Fluid–Structure Interaction Framework for Flapping, Flexible Wings
Authors: Schwab Ryan , Johnson Erick , Jankauski Mark
Published: July 2019

Fluid–structure interaction (FSI) plays a significant role in the deformation of flapping insect wings. However, many current FSI models are high-order and rely on direct computational methods, thereby limiting parametric studies as well as insights into the physics governing wing dynamics. We develop a novel flapping wing FSI framework that accommodates general wing geometry and fluid loading. We use this framework to study the unilaterally coupled FSI of an idealized hawkmoth forewing considering two fluid models: Reynolds-averaged Navier–Stokes computational fluid dynamics (RANS CFD) and blade element theory (BET). We first compare aerodynamic modal forces estimated by the low-order BET model to those calculated via high fidelity RANS CFD. We find that for realistic flapping kinematics, BET estimates modal forces five orders of magnitude faster than CFD within reasonable accuracy. Over the range flapping kinematics considered, BET and CFD estimated modal forces vary maximally by 350% in magnitude and approximately π/2 radians in phase. The large reduction in computational time offered by BET facilitates high-dimensional parametric design of flapping-wing-based technologies. Next, we compare the contributions of aerodynamic and inertial forces to wing deformation. Under the unilateral coupling assumption, aerodynamic and inertial-elastic forces are on the same order of magnitude—however, inertial-elastic forces primarily excite the wing’s bending mode whereas aerodynamic forces primarily excite the wing’s torsional mode. This suggests that, via conscientious sensor placement and orientation, biological wings may be able to sense independently inertial and aerodynamic forces.
Acoustic influence of underwater mobile survey vehicles on the soundscape of Pacific rockfish habitat
Authors: Stimpert Alison. K. , Madrigal Brijonnay C. , Wakefield W. Waldo , Yoklavich Mary M.
Published: July 2019

Noise produced by scientific equipment during fisheries surveys is largely unstudied, though these sound sources may have an effect on the organisms of interest and on their resultant stock assessments. This paper describes acoustic signatures of two underwater mobile vehicles and accompanying research ships used to survey demersal fishes, and discusses the acoustic contributions of the survey equipment to rockfish habitat. Increases in noise over ambient levels were high, but the majority of sound energy was generated by communication and navigation instrumentation on the ships and survey vehicles, and was out of the expected sensitivity range for fish hearing.
It’s not just how the game is played, it’s whether you win or lose
Authors: Molina Mario D. , Bucca Mauricio , Macy Michael W.
Published: July 2019

This article studies the effect of unequal outcomes and unequal opportunity on normative, cognitive, and affective responses.
The orphan nuclear receptor LRH-1/NR5a2 critically regulates T cell functions
Authors: Seitz Carina , Huang Juan , Geiselhöringer Anna-Lena , Galbani-Bianchi Pamela , Michalek Svenja , Phan Truong San , Reinhold Cindy , Dietrich Lea , Schmidt Christian , Corazza Nadia , Delgado M. Eugenia , Schnalzger Theresa , Schoonjans Kristina , Brunner Thomas
Published: July 2019

The nuclear receptor LRH-1 regulates T cell proliferation and is required for induction of T cell–regulated immune responses.
Stabilizing the West Antarctic Ice Sheet by surface mass deposition
Authors: Feldmann Johannes , Levermann Anders , Mengel Matthias
Published: July 2019

Collapse of the West Antarctic Ice Sheet can in principle be stopped by artificial snowfall but challenges are large and manifold.
Long-term implant of intramuscular sensors and nerve transfers for wireless control of robotic arms in above-elbow amputees
Authors: Salminger S. , Sturma A. , Hofer C. , Evangelista M. , Perrin M. , Bergmeister K. D. , Roche A. D. , Hasenoehrl T. , Dietl H. , Farina D. , Aszmann O. C.
Published: July 2019

The use of implantable myoelectric sensors showed substantial improvements in prosthetic function of above-elbow amputees.
Response to Comment on “PP2A inhibition sensitizes cancer stem cells to ABL tyrosine kinase inhibitors in BCR-ABL
+
human leukemia”
Authors: Lai Damian , Chen Min , Su Jiechuang , Liu Xiaohu , Rothe Katharina , Hu Kaiji , Forrest Donna L. , Eaves Connie J. , Morin Gregg B. , Jiang Xiaoyan
Published: July 2019

LB100 sensitizes resistant chronic phase CML stem and progenitor cells to TKIs and spares healthy bone marrow cells.
A multimodality test to guide the management of patients with a pancreatic cyst
Authors: Springer Simeon , Masica David L. , Dal Molin Marco , Douville Christopher , Thoburn Christopher J. , Afsari Bahman , Li Lu , Cohen Joshua D. , Thompson Elizabeth , Allen Peter J. , Klimstra David S. , Schattner Mark A. , Schmidt C. Max , Yip-Schneider Michele , Simpson Rachel E. , Fernandez-Del Castillo Carlos , Mino-Kenudson Mari , Brugge William , Brand Randall E. , Singhi Aatur D. , Scarpa Aldo , Lawlor Rita , Salvia Roberto , Zamboni Giuseppe , Hong Seung-Mo , Hwang Dae Wook , Jang Jin-Young , Kwon Wooil , Swan Niall , Geoghegan Justin , Falconi Massimo , Crippa Stefano , Doglioni Claudio , Paulino Jorge , Schulick Richard D. , Edil Barish H. , Park Walter , Yachida Shinichi , Hijioka Susumu , van Hooft Jeanin , He Jin , Weiss Matthew J. , Burkhart Richard , Makary Martin , Canto Marcia I. , Goggins Michael G. , Ptak Janine , Dobbyn Lisa , Schaefer Joy , Sillman Natalie , Popoli Maria , Klein Alison P. , Tomasetti Cristian , Karchin Rachel , Papadopoulos Nickolas , Kinzler Kenneth W. , Vogelstein Bert , Wolfgang Christopher L. , Hruban Ralph H. , Lennon Anne Marie
Published: July 2019

Molecular and clinical markers outperform current clinical and imaging criteria for the diagnosis and management of patients with pancreatic cysts.
Diverse compositions and functions of chromatin remodeling machines in cancer
Authors: Kadoch Cigall
Published: July 2019

Human cancer genetics power biochemical and functional interrogation of chromatin remodeling complexes, informing therapeutic opportunities.
Biopearling of Interconnected Outer Membrane Vesicle Chains by a Marine Flavobacterium
Authors: Fischer Tanja , Schorb Martin , Reintjes Greta , Kolovou Androniki , Santarella-Mellwig Rachel , Markert Stephanie , Rhiel Erhard , Littmann Sten , Becher Dörte , Schweder Thomas , Harder Jens
Published: July 2019

Microorganisms produce membrane vesicles. One synthesis pathway seems to be pearling that describes the physical formation of vesicle chains from phospholipid vesicles via extended tubes. Bacteria with vesicle chains had been observed as well as bacteria with tubes, but pearling was so far not observed. Here, we report the observation of, initially, tubes and then vesicle chains during the growth of a flavobacterium, suggesting biopearling of vesicle chains. The flavobacterium is abundant during spring bacterioplankton blooms developing after algal blooms and has a special set of enzymes for laminarin, the major storage polysaccharide of microalgae. We demonstrated with fluorescently labeled laminarin that the vesicle chains bind laminarin or contain laminarin-derived compounds. Proteomic analyses revealed surface-attached degradative enzymes on the outer membrane vesicles. We conclude that the large surface area and the lumen of vesicle chains may contribute to the ecological success of this marine bacterium.
Plastics: Environmental and Biotechnological Perspectives on Microbial Degradation
Authors: Danso Dominik , Chow Jennifer , Streit Wolfgang R.
Published: July 2019

Plastics are widely used in the global economy, and each year, at least 350 to 400 million tons are being produced. Due to poor recycling and low circular use, millions of tons accumulate annually in terrestrial or marine environments. Today it has become clear that plastic causes adverse effects in all ecosystems and that microplastics are of particular concern to our health.
Amino Acids and Ribose: Drivers of Protein and RNA Fermentation by Ingested Bacteria of a Primitive Gut Ecosystem
Authors: Zeibich Lydia , Staege Maraike , Schmidt Oliver , Drake Harold L.
Published: July 2019

Animal health is linked to gut ecosystems whose primary function is normally the digestion of dietary matter. Earthworms are representative of one of the oldest known animal lineages and, despite their primitive nature, have unique environmental impact by virtue of their dietary consumption of their habitat, i.e., soil-associated matter. A resident gut community is a hallmark of many gut ecosystems of evolutionarily more advanced animals, but the alimentary canal of earthworms is dominated by ingested transient soil microbes. Protein and RNA are (i) the primary organic components of microbial cells that are subject to lysis during gut passage and (ii) fermentable dietary substrates in the alimentary canal. This study examined the gut-associated fermentation of constituents of these biopolymers to determine how their fermentation is integrated to the microbiological dynamics of the gut and might contribute to earthworm-linked transformations of organic matter in the terrestrial biosphere.
Genome Sequence of Lactobacillus plantarum KB1253, a Gamma-Aminobutyric Acid (GABA) Producer Used in GABA-Enriched Tomato Juice Production
Authors: Nakatani Yuki , Fukao Masanori , Fukaya Tetsuya
Published: July 2019

Here, we present the draft genome sequence of
Lactobacillus plantarum
KB1253, isolated from a traditional Japanese pickle. Its genome comprises 3,097 genes and 3,305,456 nucleotides, with an average G+C content of 44.4%.
Draft Genome Sequence of
Paracoccus
sp. Strain 228, Isolated from Surface Water of the Gulf of Gdańsk in the Baltic Sea
Authors: Karczewska-Golec Joanna , Kochanowska-Łyżen Maja , Bałut Magdalena , Piotrowski Arkadiusz , Golec Piotr , Szalewska-Pałasz Agnieszka
Published: July 2019

We present here the draft genome sequence of
Paracoccus
sp. strain 228, isolated from the Gulf of Gdańsk in the southern part of the Baltic Sea. The assembly contains 4,131,609 bp in 32 scaffolds.
Complete Genome Sequence of the Diatom-Associated Bacterium
Sphingorhabdus
sp. Strain SMR4y
Authors: Töpel Mats , Pinder Matthew I. M. , Johansson Oskar N. , Kourtchenko Olga , Godhe Anna , Clarke Adrian K.
Published: July 2019

The bacterial strain SMR4y belongs to the diverse microbiome of the marine diatom
Skeletonema marinoi
strain R05AC. After assembly of its genome, presented here, and subsequent analyses, we placed it in the genus
Sphingorhabdus
. This strain has a 3,479,724-bp circular chromosome (with 3,340 coding sequences) and no known plasmids.
Draft Genome Sequence of a Fermenting Bacterium,
Soehngenia
sp. Strain 1933P, Isolated from a Petroleum Reservoir in Azerbaijan
Authors: Grouzdev Denis S. , Bidzhieva Salimat K. , Sokolova Diyana S. , Tourova Tatiyana P. , Poltaraus Andrey B. , Nazina Tamara N.
Published: July 2019

The draft genome sequence of a mesophilic fermenting bacterium,
Soehngenia
sp. strain 1933P, isolated from production water of the Binagady petroleum reservoir (Republic of Azerbaijan), is presented. The genome is annotated for elucidation of the metabolic potential and taxonomic position of strain 1933P.
Complete Genome Sequence of Serratia marcescens Myophage Moabite
Authors: Price Lyndsey , Rohren Matthew , Newkirk Heather , Liu Mei , Ramsey Jolene
Published: July 2019

Serratia marcescens
is a Gram-negative nosocomial pathogen causing various hospital-acquired infections. Here, we describe the complete genome sequence of
S. marcescens
myophage Moabite. The genome of Moabite is 273,933 bp long, with 337 predicted coding sequences and two tRNA genes, and it shares its highest amino acid identity with
Serratia
phage 2050HW.
Renal failure caused by severe pelvic organ prolapse
Authors: Lucassen Eliane A , la Chapelle Claire F , Krouwel Esmee , Groeneveld Marc
Published: July 2019

Pelvic organ prolapse (POP), the transvaginal descent of pelvic organs, can cause mild hydronephrosis but rarely leads to a deterioration in kidney function. We present a case of severe uterovaginal prolapse that caused bilateral ureteral obstruction and led to renal failure and urinary tract infection. During outpatient follow-up, kidney function had already been deteriorating, but POP was not recognised as a causal factor. A longer duration of ureteral obstruction can lead to irreversible kidney damage, and therefore, timely recognition and intervention is of essence. Even in complex cases with various causative factors for kidney injury, the presence of severe POP and kidney injury should prompt the clinician to exclude this cause.
The Italian preparticipation evaluation programme: diagnostic yield, rate of disqualification and cost analysis
Authors: Vessella Teresina , Zorzi Alessandro , Merlo Laura , Pegoraro Cinzia , Giorgiano Flaviano , Trevisanato Michele , Viel Mirella , Formentini Pietro , Corrado Domenico , Sarto Patrizio
Published: July 2019

Introduction

Italian law mandates that every competitive athlete must undergo annual preparticipation evaluation (PPE) to identify cardiovascular (CV) diseases that pose a risk of sudden death (SD) during sport and other conditions that may threaten the athlete’s health. We investigated the diagnostic yield, rate of disqualification and costs of our PPE.

Methods

We included 5910 consecutive apparently healthy athletes (61% males, mean age 15±4 years) who underwent annual PPE performed by a sports medicine specialist. The PPE included history, physical examination, weight, height and blood pressure measurement, test of visual acuity, spirometry, urine chemistry, resting 12-lead ECG and exercise testing with ECG monitoring. In cases of abnormal findings, we carried out second-line investigations.

Results

During a 12-month study period, 5.326 (90.2%) athletes were cleared for competition after a normal first-line evaluation and 584 (9.8%) underwent one or more further examinations. Of those, 88 (1.5%) were diagnosed to have a CV disease (including 18 (0.3%) at-risk of SD) and 31 (0.5%) had a non-CV diagnosis. A total of 32 (0.5%) athletes were temporarily (n=15) or permanently (n=17) disqualified from competitive sports. The average cost per athlete was €79, which consisted of €64 (80%) for first-line evaluations and €15 (20%) for additional investigations.

Conclusion

PPE according to the Italian model identified a range of diseases in 2.0% of apparently healthy athletes at an average cost of €79.
Spending on World Health Organization essential medicines in Medicare Part D, 2011-15: retrospective cost analysis
Authors: Li David G , Najafzadeh Mehdi , Kesselheim Aaron S , Mostaghimi Arash
Published: July 2019

Objectives

To characterize the trends, drivers, and potential modifiers of increased spending by US Medicare beneficiaries on medicines deemed essential by the World Health Organization.

Design

Retrospective cost analysis of Medicare Part D Prescriber Public Use File, detailing annual generic and brand name drug prescribing and spending from 2011 through 2015 by Medicare Part D participants who filled prescriptions for WHO essential medicines.

Setting

US Medicare System.

Main outcome measures

Total and per beneficiary Medicare spending, total and per beneficiary out-of-pocket patient spending, cumulative beneficiary count, claim count, and per unit drug cost. All spending measures were adjusted for inflation and reported in 2015 US dollars.

Results

Medicare Part D expenditures on 265 WHO essential medicines between 2011 and 2015 was $87.2bn (£68.4bn; €76.5bn), with annual spending increasing from $11.9bn in 2011 to $25.8bn in 2015 (116%). Patients’ out-of-pocket spending for essential medicines over the same period was $12.1bn. Total annual out-of-pocket spending increased from $2.0bn to $2.9bn (47%), and annual per beneficiary out-of-pocket spending on these drugs increased from $20.42 to $21.17 (4%). Total prescription count increased from 376.1m to 498.9m (33%), and cumulative beneficiary count grew from 95.9m to 135.8m (42%). Of the essential medicines included in the study, the per unit cost of 133 (50%) agents increased faster than the average inflation rate during this period. Overall, approximately 58% of the increase in total spending during this period can be attributed to the introduction of novel agents.

Conclusions

Spending associated with essential medicines grew substantially from 2011 to 2015, driven largely by the increased use of two expensive novel drugs used in treating hepatitis C. Approximately 22% of increased total spending during this period can be attributed to increases in per unit cost of existing drugs. These trends may limit patients’ access to essential drugs while also increasing healthcare system costs.
Descriptive analysis of real-world medication use pattern of statins and antiplatelet agents among patients with acute coronary syndrome in Hong Kong and the USA
Authors: Wang Yun , Nichol Michael B , Yan Bryan PY , Wu Joanne , Tomlinson Brian , Lee Vivian WY
Published: July 2019

Objectives

The objective was to explore the differences in medication use pattern of lipid-lowering drug (LLD) and antiplatelet agents among post-percutaneous coronary intervention patients with acute coronary syndrome aged <65 in Hong Kong (HK) and the USA.

Design

Retrospective study.

Setting

This study used deidentified claims data from Clinformatics Data Mart database (OptumInsight, Eden Prairie, Minnesota, USA) and electronic health records from HK Hospital Authority Clinical Data Analysis and Reporting System database.

Participants

We used 1 year prescription records of LLDs and antiplatelet agents among 1013 USA patients and 270 HK Chinese patients in 2011–2013.

Primary and secondary outcome measures

Continuity was investigated on the assumption that one defined daily dose represented 1 day treatment. Medication possession ratio method was used to evaluate the adherence. Multivariate-adjusted logistic regressions were constructed to compare the good continuity and adherence levels in the merged database with the cutoffs set at 80%, and Cox proportional hazard models were built using the time to discontinuation as the dependent variable, to assess the persistence level.

Results

HK Chinese patients were less adherent (67.41% vs 84.60%, adjusted odds ratio (AOR) for Americans over Chinese=2.23 (95% CI=1.60 to 3.12), p<0.001) to antiplatelet agents compared with American patients but better adherent to statins (90.00% vs 78.18%, AOR=0.37 (0.23 to 0.58), p<0.001). The discontinuation with statins was more common in American patients (13.33% vs 34.25%, adjusted hazard ratio (AHR)=2.95 (2.05 to 4.24), p<0.001). Low-to-moderate potency statins and clopidogrel were favoured by our HK local physicians, while American patients received higher doses of statins and prasugrel.

Conclusions

We seemed to find HK physicians tended to prescribe cheaper and lower doses of statins and antiplatelet agents when compared with the privately insured patients in the USA, though the adherence and persistence levels of HK patients with statins were relatively good.
National medical expenditures by smoking status in American adults: an application of Manning’s two-stage model to nationally representative data
Authors: Swedler David I , Miller Ted R , Ali Bina , Waeher Geetha , Bernstein Steven L
Published: July 2019

Objectives

To assess the medical expenditures of American adults by their smoking status—Current, Former or Never smokers. We update these expenditures through 2015 controlling for personal characteristics and medical history and assess the impact of years-since-quitting and decade of life.

Setting and participants

Weighted sample of American adults, 2011–2015. The linked National Health Interview Survey (NHIS) and Medical Expenditure Panel Survey (MEPS) are annual weighted representations of approximately 250 million adults. Sampling of NHIS is multistage with data collected throughout the year.

Primary outcome measures

Using data from NHIS and MEPS, we collected demographic data, self-reported medical history and current smoking status. Smoking status was designated as Never, Current and Former, along with years-since-quitting. Total medical expenditures were collected from MEPS for 2011–2015. We used Manning’s two-part model to estimate average expenditures per individual and marginal costs for individuals at all levels of smoking status.

Results

American adults averaged US$4830 in average medical expenditures. Never smokers (US$4360, 95% CI 4154.3 to 4566.3), had lower expenditures than Current (US$5244, 95% CI 4707.9 to 5580.3) and Former (US$5590, 95% CI 5267.4 to 5913.5) smokers. CI for Current and Former smokers overlapped. Results were similarly significant when controlling for disease history. Years-since-quitting did not affect expenditures. In each decade of adult life, Former smokers had the highest annual medical expenditures, followed by Current and then Never smokers.

Conclusions

We updated annual medical expenditures during the Affordable Care Act era by smoking status using the current best practice model. While we identify Former smokers as having higher medical expenditures than Current smokers, we do not examine how care-seeking behaviour varies between levels of each risk factor.
Methodology for developing and evaluating food-based dietary guidelines and a Healthy Eating Index for Ethiopia: a study protocol
Authors: Bekele Tesfaye Hailu , de Vries Jeanne JHM , Trijsburg Laura , Feskens Edith , Covic Namukolo , Kennedy Gina , Brouwer Inge D
Published: July 2019

Introduction

Food-based dietary guidelines (FBDGs) are used to promote and maintain healthy eating in a population, by providing country-specific guidance. However, many African countries like Ethiopia do not have FBDGs. This paper describes the methodology for the development of Ethiopian FBDGs and for creating and evaluating a Healthy Eating Index and a scoring tool that can be used to monitor the adherence of the population to FBDGs.

Methods and analysis

A multidisciplinary technical working group will be tasked to develop FBDGs for the general population above 2 years of age based on identification of priority diet-related public health problems and risk factors, and a systematic review of dietary patterns in relation to the identified priority health outcomes, following a multistep process. FBDGs will be translated into daily food choices for specific subpopulations by applying linear programming using data from the National Food Consumption Survey (NFCS) of 2011. FBDGs will be evaluated for cultural appropriateness, acceptability, consumer understanding and practicality. A dietary gap assessment will be conducted by comparing the national food supply with the country’s food demand. In addition an Ethiopian Healthy Eating Index (EHEI) will be developed based on the FBDGs using the NFCS data. The EHEI will be evaluated by comparing the EHEI Score based on 24 hours diet recall with that of the EHEI Score based on a Food Frequency Questionnaire, by analysing the association of the EHEI Score with population characteristics and micronutrient intake with or without additional adjustment for energy intake. Finally, a brief Food Quality Screening tool scoring for the important EHEI components will be developed to enable evaluation for counselling.

Ethics and dissemination

Ethical approval is received from the Scientific and Ethical Review Office of the Ethiopian Public Health Institute. The findings will be disseminated through peer-reviewed publications.A dissemination workshop will be organised with key implementing sectors of the food system for a healthier diet (http://a4nh.cgiar.org/our-research/research-flagships/) and with key public and private partners. The findings from this study will be translated into FBDGs and shared through conferences, reports and the mass media (TV and radio).

Trial registration number

NCT03394963; Pre-results.
Cochrane systematic review and meta-analysis of botulinum toxin for the prevention of migraine
Authors: Herd Clare P , Tomlinson Claire L , Rick Caroline , Scotton William J , Edwards Julie , Ives Natalie J , Clarke Carl E , Sinclair AJ
Published: July 2019

Objectives

To assess the effects of botulinum toxin for prevention of migraine in adults.

Design

Systematic review and meta-analysis.

Data sources

CENTRAL, MEDLINE, Embase and trial registries.

Eligibility criteria

We included randomised controlled trials (RCTs) of botulinum toxin compared with placebo, active treatment or clinically relevant different dose for adults with chronic or episodic migraine, with or without the additional diagnosis of medication overuse headache.

Data extraction and synthesis

Cochrane methods were used to review double-blind RCTs. Twelve week post-treatment time-point data was analysed.

Results

Twenty-eight trials (n=4190) were included. Trial quality was mixed. Botulinum toxin treatment resulted in reduced frequency of −2.0 migraine days/month (95% CI −2.8 to −1.1, n=1384) in chronic migraineurs compared with placebo. An improvement was seen in migraine severity, measured on a numerical rating scale 0 to 10 with 10 being maximal pain, of −2.70 cm (95% CI −3.31 to −2.09, n=75) and −4.9 cm (95% CI −6.56 to −3.24, n=32) for chronic and episodic migraine respectively. Botulinum toxin had a relative risk of treatment related adverse events twice that of placebo, but a reduced risk compared with active comparators (relative risk 0.76, 95% CI 0.59 to 0.98) and a low withdrawal rate (3%). Although individual trials reported non-inferiority to oral treatments, insufficient data were available for meta-analysis of effectiveness outcomes.

Conclusions

In chronic migraine, botulinum toxin reduces migraine frequency by 2 days/month and has a favourable safety profile. Inclusion of medication overuse headache does not preclude its effectiveness. Evidence to support or refute efficacy in episodic migraine was not identified.
Lowering blood pressure after acute intracerebral haemorrhage: protocol for a systematic review and meta-analysis using individual patient data from randomised controlled trials participating in the Blood Pressure in Acute Stroke Collaboration (BASC)
Authors: Moullaali Tom J , Wang Xia , Woodhouse Lisa J , Law Zhe Kang , Delcourt Candice , Sprigg Nikola , Krishnan Kailash , Robinson Thompson G , Wardlaw Joanna M , Al-Shahi Salman Rustam , Berge Eivind , Sandset Else C , Anderson Craig S , Bath Philip M
Published: July 2019

Introduction

Conflicting results from multiple randomised trials indicate that the methods and effects of blood pressure (BP) reduction after acute intracerebral haemorrhage (ICH) are complex. The Blood pressure in Acute Stroke Collaboration is an international collaboration, which aims to determine the optimal management of BP after acute stroke including ICH.

Methods and analysis

A systematic review will be undertaken according to the Preferred Reporting Items for Systematic review and Meta-Analysis of Individual Participant Data (IPD) guideline. A search of Cochrane Central Register of Controlled Trials, EMBASE and MEDLINE from inception will be conducted to identify randomised controlled trials of BP management in adults with acute spontaneous (non-traumatic) ICH enrolled within the first 7 days of symptom onset. Authors of studies that meet the inclusion criteria will be invited to share their IPD. The primary outcome will be functional outcome according to the modified Rankin Scale. Safety outcomes will be early neurological deterioration, symptomatic hypotension and serious adverse events. Secondary outcomes will include death and neuroradiological and haemodynamic variables. Meta-analyses of pooled IPD using the intention-to-treat dataset of included trials, including subgroup analyses to assess modification of the effects of BP lowering by time to treatment, treatment strategy and patient’s demographic, clinical and prestroke neuroradiological characteristics.

Ethics and dissemination

No new patient data will be collected nor is there any deviation from the original purposes of each study where ethical approvals were granted; therefore, further ethical approval is not required. Results will be reported in international peer-reviewed journals.

PROSPERO registration number

CRD42019141136.
Expression of the type 3 InsP3receptor is a final common event in the development of hepatocellular carcinoma
Authors: Guerra Mateus T , Florentino Rodrigo M , Franca Andressa , Lima Filho Antonio C , dos Santos Marcone L , Fonseca Roberta C , Lemos Fernanda O , Fonseca Matheus C , Kruglov Emma , Mennone Albert , Njei Basile , Gibson Joanna , Guan Fulan , Cheng Yung-Chi , Ananthanarayanam Meenakshisundaram , Gu Jianlei , Jiang Jianping , Zhao Hongyu , Lima Cristiano X , Vidigal Paula T , Oliveira Andre G , Nathanson Michael H , Leite Maria Fatima
Published: July 2019

Background & objectives

Hepatocellular carcinoma (HCC) is the second leading cause of cancer death worldwide. Several types of chronic liver disease predispose to HCC, and several different signalling pathways have been implicated in its pathogenesis, but no common molecular event has been identified. Ca2+signalling regulates the proliferation of both normal hepatocytes and liver cancer cells, so we investigated the role of intracellular Ca2+release channels in HCC.

Design

Expression analyses of the type 3 isoform of the inositol 1, 4, 5-trisphosphate receptor (ITPR3) in human liver samples, liver cancer cells and mouse liver were combined with an evaluation of DNA methylation profiles of ITPR3 promoter in HCC and characterisation of the effects of ITPR3 expression on cellular proliferation and apoptosis. The effects ofde novoITPR3 expression on hepatocyte calcium signalling and liver growth were evaluated in mice.

Results

ITPR3 was absent or expressed in low amounts in hepatocytes from normal liver, but was expressed in HCC specimens from three independent patient cohorts, regardless of the underlying cause of chronic liver disease, and its increased expression level was associated with poorer survival. TheITPR3gene was heavily methylated in control liver specimens but was demethylated at multiple sites in specimens of patient with HCC. Administration of a demethylating agent in a mouse model resulted in ITPR3 expression in discrete areas of the liver, and Ca2+signalling was enhanced in these regions. In addition, cell proliferation and liver regeneration were enhanced in the mouse model, and deletion ofITPR3from human HCC cells enhanced apoptosis.

Conclusions

These results provide evidence thatde novoexpression of ITPR3 typically occurs in HCC and may play a role in its pathogenesis.
Interaction of ischaemic postconditioning and thrombectomy in patients with ST-elevation myocardial infarction
Authors: Nepper-Christensen Lars , Høfsten Dan Eik , Helqvist Steffen , Lassen Jens Flensted , Tilsted Hans-Henrik , Holmvang Lene , Pedersen Frants , Joshi Francis , Sørensen Rikke , Bang Lia , Bøtker Hans Erik , Terkelsen Christian Juhl , Maeng Michael , Jensen Lisette Okkels , Aarøe Jens , Kelbæk Henning , Køber Lars , Engstrøm Thomas , Lønborg Jacob
Published: July 2019

Objective

The Third Danish Study of Optimal Acute Treatment of Patients with ST-segment Elevation Myocardial Infarction – Ischaemic Postconditioning (DANAMI-3-iPOST) did not show improved clinical outcome in patients with ST-segment elevation myocardial infarction (STEMI) treated with ischaemic postconditioning. However, the use of thrombectomy was frequent and thrombectomy may in itself diminish the effect of ischaemic postconditioning. We evaluated the effect of ischaemic postconditioning in patients included in DANAMI-3-iPOST stratified by the use of thrombectomy.

Methods

Patients with STEMI were randomised to conventional primary percutaneous coronary intervention (PCI) or ischaemic postconditioning plus primary PCI. The primary endpoint was a combination of all-cause mortality and hospitalisation for heart failure.

Results

From March 2011 until February 2014, 1234 patients were included with a median follow-up period of 35 (interquartile range 28 to 42) months. There was a significant interaction between ischaemic postconditioning and thrombectomy on the primary endpoint (p=0.004). In patients not treated with thrombectomy (n=520), the primary endpoint occurred in 33 patients (10%) who underwent ischaemic postconditioning (n=326) and in 35 patients (18%) who underwent conventional treatment (n=194) (adjusted hazard ratio (HR) 0.55 (95%confidence interval (CI) 0.34 to 0.89), p=0.016). In patients treated with thrombectomy (n=714), there was no significant difference between patients treated with ischaemic postconditioning (n=291) and conventional PCI (n=423) on the primary endpoint (adjusted HR 1.18 (95% CI 0.62 to 2.28), p=0.62).

Conclusions

In this post-hoc study of DANAMI-3-iPOST, ischaemic postconditioning, in addition to primary PCI, was associated with reduced risk of all-cause mortality and hospitalisation for heart failure in patients with STEMI not treated with thrombectomy.

Trial registration number

NCT01435408.
Effects of high-intensity interval training on platelet function in cardiac rehabilitation: a randomised controlled trial
Authors: Heber Stefan , Fischer Beatrix , Sallaberger-Lehner Marina , Hausharter Maria , Ocenasek Helmuth , Gleiss Andreas , Fischer Michael J M , Pokan Rochus , Assinger Alice , Volf Ivo
Published: July 2019

Objective

To compare effects of moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) on platelet function in patients undergoing cardiac rehabilitation, as hyper-reactive platelets are involved in atherogenesis and atherothrombosis.

Methods

In this single-centre parallel group randomised controlled trial, male patients after an acute coronary syndrome under dual antiplatelet therapy performed MICT or HIIT+MICT for 12 weeks. Main outcome was platelet reactivity measured by the half-maximal concentration (EC50) of platelet agonist thrombin receptor-activating peptide-6 (TRAP-6) in terms of P-selectin expression. EC50was determined at baseline, after 6 and 12 weeks, each time at physical rest and on exertion.

Results

82 patients were randomised to MICT or HIIT+MICT. Mean (95% CI) baseline EC50values at physical rest were 6.7 µM (6.3 µM to 7.0 µM) TRAP-6. After 6/12 weeks, 36/33 MICT and 34/28 HIIT+MICT patients were examined. HIIT+MICT patients had 0.9 µM (0.4 µM to 1.4 µM)/0.5 µM (−0.1 µM to 1.0 µM) higher EC50values than MICT ones, and the propensity of their platelets to form aggregates with monocytes was significantly lower after 12 weeks. Short-term strenuous physical exertion was generally associated with platelet activation and an EC50reduction of 0.7 µM (0.6 µM to 0.8 µM). HIIT+MICT patients tended to be fitter after 12 weeks. No serious harms were observed.

Conclusions

Including HIIT in cardiac rehabilitation seems to confer additional benefits compared with MICT alone, which should be confirmed in clinical trials with hard endpoints. Exertion-induced platelet activation and hyper-reactivity occur despite dual antiplatelet therapy.

Trial registration number

NCT02930330; Results.
Oral levosimendan in amyotrophic lateral sclerosis: a phase II multicentre, randomised, double-blind, placebo-controlled trial
Authors: Al-Chalabi Ammar , Shaw Pamela , Leigh P Nigel , van den Berg Leonard , Hardiman Orla , Ludolph Albert , Aho Valtteri V , Sarapohja Toni , Kuoppamäki Mikko
Published: July 2019

Objective

To evaluate the efficacy and safety of oral levosimendan in patients with amyotrophic lateral sclerosis (ALS). This phase II, randomised, double-blind, placebo-controlled, crossover, three-period study with 6 months open-label follow-up enrolled adults with ALS and sitting slow vital capacity (SVC) 60%–90 % of predicted from 11 sites in four countries.

Methods

Patients received levosimendan 1 mg daily, 1 mg two times a day or placebo during three 14-day crossover periods and levosimendan 1–2 mg daily during open-label follow-up. Primary endpoint was sitting SVC; secondary endpoints included supine SVC, ALS Functional Rating Scale-Revised (ALSFRS-R), tolerability and safety.

Results

Of 66 patients randomised, 59 contributed to the double-blind results and 50 entered open-label follow-up. Sitting SVC was not significantly different between the treatments. In post hoc analysis using period-wise baselines, supine SVC favoured levosimendan over placebo, estimated mean differences from baseline being −3.62% on placebo, +0.77% on levosimendan 1 mg daily (p=0.018) and +2.38% on 1 mg two times a day (p=0.001). Headache occurred in 16.7% of patients during levosimendan 1 mg daily (p=0.030), 28.6% during 1 mg two times a day (p=0.002) and 3.3% during placebo. The respective frequencies for increased heart rate were 5.1% (p=0.337), 18.5% (p=0.018) and 1.7%. No significant differences between the treatments were seen for other adverse events.

Conclusions

Levosimendan did not achieve the primary endpoint of improving sitting SVC in ALS. Headache and increased heart rate were increased on levosimendan, although it was otherwise well tolerated. A phase III study to evaluate the longer term effects of oral levosimendan in ALS is ongoing.