bluuebunny/crossref_metadata_2025 huggingface dataset:
Design of a Wearable Health Monitoring System for In-Home and Emergency Use
Authors: Bertsch J. Michael , Gent Stephen P.
Published: August 2020

Recent advancements in wearable medical technologies have streamlined health monitoring with simple, non-invasive measurements. These devices, however, are rarely capable of monitoring all the necessary parameters for an accurate measure of health, such as blood pressure, and can cost the user hundreds to thousands of dollars. The objective of this project was to design an affordable, user-friendly, wearable device capable of monitoring multiple parameters: body temperature, blood pressure, heart rate, blood oxygen, and body positioning. By combining wearable sensors with Inter-Integrated Circuit (I2C) technology, the data from many sensors can be transmitted while maintaining a compact size for a wearable. In parallel with this device, a mobile application was designed as an interface to receive real-time comprehensive measurements. This device could be used to reduce monitor application time in emergency medical settings and monitor patients in rural communities who are often hours away from the nearest medical centers.
Surface Profile and Third-Body Layer Accumulation Measurement Using a 3D Laser Profiler
Authors: Radmehr Ahmad , Hosseinian Ahangarnejad Arash , Tajaddini Ali , Ahmadian Mehdi
Published: August 2020

The surface profile wear and the resulting third-body layer accumulation are investigated on the Virginia Tech-Federal Railroad Administration Roller Rig (VT-FRA Roller Rig), using a high-precision 3D laser profiler by Keyence. It is observed that the wheel surface gradually wears and the fine worn material accumulates on the running surfaces. It is further observed that with the progression of the wear and accumulation of a powder-like material at running surface, a preocular change in wheel-rail traction occurs. The first step in exploring the physics of the changes in traction is quantifying, precisely, the micron-sized surface finish changes and wear material accumulation. This paper provides the process of choosing a suitable surface profiler for the VT-FRA roller rig adaptation, and the results of a series of tests under various wheel load and contact configurations.

A baseline experiment is conducted to evaluate the wheel wear and the accumulation of the naturally-generated third body layer (the worn material) on the wheel’s running surface. Before each series of experiments, the wheel and roller running surfaces were polished and thoroughly cleaned to make sure that they are perfectly smooth (finished) and free of any debris or dust. The wheel surface profile is measured in the perfectly cleaned condition using the 3D laser scanner. Time controlled experiments are run with different wheel loads, % slippage, and angle of attack (AoA) for 500 seconds. For each run, the change with surface finish and accumulated third body layer build up is measured.

It is consistently observed that the traction forces increase gradually with time until they reach a stable level, presented by a plateau in the traction-slippage curves. The time to reach the plateau is directly related to wheel’s dynamic conditions including load, %slippage, and AOA. For some of the conditions, such as wheel load, the relationship is linear and for others (such as AOA) it is nonlinear. Concentrating on the analysis of the baseline results, it is observed that the change in surface finish and the third body layer that naturally accumulates at the running surface — hence, referred to as “natural third body layer” or “NTBL” — is directly correlated and somewhat linearly with NTBL and change in the running surface from smooth to rough. The correlation is most noticeable for the NTBL. With increasing NTBL, traction increases rapidly until the running surface is saturated with the accumulated wear material, presumably a ferrous oxide. There is far weaker correlation between the change in surface finish and traction variations. It is noticed that the surface finish continues to change beyond the time that the traction forces reach their plateau, and its effect remains far more gradual than NTBL.
Smart Bridge: Autonomous Structural Integrity Monitor for Railroad Bridges
Authors: Smith Frank J.
Published: August 2020

This paper provides an introduction to Smart Bridge; a railroad bridge structural integrity monitoring system based on Continuous Fiber Optic Strain Sensing (CFOSS) technology. This design concept allows for the real time observation of how a bridge responds to dynamic loading and provides for autonomous reporting of abnormal structural conditions.

The CFOSS technology can monitor the entire bridge and observe changes in the behavure of its structural elements. The structure is constantly monitored, both when the structure is at static load and when the bridge is supporting the load of a train. When significant changes are observed they can be defined by location and the degree of deviation from normal.

A Smart Bridge provides automatic notification of sudden changes to the structure in real time. These changes may be an indication of bridge impact damage. It also provides a graphical map of the changes in structural behavure over time. In both circumstances the technology will identify the specific structural element that is degrading.

Smart Bridge is based on Continuous Fiber Optic Strain Sensing technology. This technology manifests in the form of a cable that is bonded along the entire length of the structural elements of the bridge. The cable senses strain in both the axial and transverse directions. Unlike conventional strain gauge elements that are bonded to a single location, CFOSS cables run continuously along the beam, plate or tendon. The technology is able to observe the changes in the concentration of strain along a structure and identify the origin of the change.

CFOSS technology is currently under development as part of the Smart Rail project. The underlying fiber optic strain sensing cable technology is in commercial use in the oil well and petrochemical pipeline industry.

The adoption of Smart Bridge provides enhanced operational safety because it monitors the structural integrity of the bridge continuously and provides automatic status annunciations. This monitoring is active during times when the bridge is in dead load and when it is supporting the load of a passing train. Smart Bridge also improves the working safety of bridge inspectors by providing a map of structural changes that may indicate hazardous conditions. The use of Smart Bridge improves the inspection process by identifying potential structural problems that may require visual confirmation. And it provides autonomous warnings when sudden changes in the bridge structural integrity are detected.
A Literature Review on Rail Transport of Hazmat Release Risk Analysis
Authors: Bian Zheyong , Liu Xiang
Published: August 2020

Rail plays an important role in hazmat transportation, transporting over two million carloads of hazardous materials (hazmat) in the United States annually. Compared with a truck trailer carrying a single hazmat car, a train has much more severe consequence of hazmat release due to carrying multiple connected hazmat cars (e.g., 50 to 120 flammable liquid cars). It is of high priority for the government and railroad companies to enhance the railroad hazmat transportation safety since the train accidents can cause severe railroad hazmat release incidents. Based on the data provided by Federal Railroad Administration (FRA) of the U.S. Department of Transportation (U.S.DOT), there are over 300 accident causes, including infrastructure failure defects, rolling stock failures, human errors, weather conditions, etc. It is significant to understand the relationship between hazmat transportation risk and accident cause to provide guidance for developing, evaluating, and prioritizing accident prevention strategies, thereby mitigating hazmat transportation risk. Therefore, this paper reviews the literature on rail transport of hazmat release risk analysis in order to capture the event chain leading to hazmat release, possible risk factors, and the state of the art on existing risk analysis methodologies.

We reviewed the related references based on a five-step process: (1) train accident occurrence, (2) number of cars derailed, (3) number of hazardous material cars derailed, (4) number of hazmat cars releasing, and (5) release consequences. First, many severe hazmat release incidents are caused by train accidents, particularly train derailments. Prior research found that over 70% of freight train mainline derailments were caused by either infrastructure defects or rolling stock failures. Possible strategies for reducing the probability of train accidents include the prevention of track defects, equipment condition monitoring to reduce in-service failures, and the use of more advanced train control technologies to reduce human error. Second, number of cars derailed is an important factor causing hazmat releasing. Based on the reviewed literature, the total number of cars derailed depends on accident cause, speed, train length, and point of derailment. Third, the literature implied that the total number of hazmat cars derailed is related to train length, number of hazmat cars and non-hazmat cars in a train, and their placement. Fourth, the number of hazmat cars releasing contents is influenced by hazardous materials car safety design, accident speed, etc. Finally, the consequences of a release can be measured by different metrics, such as property damage, environmental impact, traffic delay, or the affected population. Geographical information systems (GIS) can be used for consequence analysis integrated with other databases such as census and rail network data.
CFD Verification and Validation Exercise: Turbulent Mixing of Stratified Layer
Authors: Thompson Jason , Boyd Christopher
Published: August 2020

The US Nuclear Regulatory Commission (NRC) participated in an Organization for Economic Cooperation and Development / Nuclear Energy Agency (OECD/NEA) benchmark activity based on testing in the PANDA facility located at the Paul Scherrer Institute in Switzerland. In this test, a stratified helium layer was eroded by a turbulent jet from below. NRC participated in this benchmark to develop expertise and modeling guidelines for computational fluid dynamics (CFD) in anticipation of utilizing these methods for future safety and confirmatory analyses. CFD predictions using ANSYS FLUENT V19.0 are benchmarked using the PANDA test data, and sensitivity studies are used to evaluate the significance of key phenomena, such as boundary conditions and modeling options, that impact the helium erosion rates and jet velocity distribution. The k-epsilon realizable approach with second order differencing resulted in the best prediction of the test data. The most significant phenomena are found to be the inlet mass flowrate and turbulent Schmidt number. CFD uncertainty for helium and velocity due to numerical error and input parameter uncertainty are predicted using a sensitivity coefficient approach. Numerical uncertainty resulting from the mesh design is estimated using a Grid Convergence Index (GCI) approach. Meshes of 0.5, 1.5 (base mesh), and 4.5 million cells are used for the GCI. Approximately second order grid convergence was observed but p (order of convergence) values from 1 to 5 were common. The final helium predictions with one-sigma uncertainty interval generally bounded the experimental data. The predicted jet centerline velocity was approximately 50% of the measured value at multiple measurement locations. This velocity benchmark is likely affected by the difference in the He content between the experiment and prediction. The predicted jet centerline velocity with the one-sigma uncertainty interval did not bound the experimental data.
On the Role of Discretization Errors in the Quantification of Parameter Uncertainties
Authors: Eça Luís , Pereira Filipe S. , Vaz Guilherme , Lopes Rui , Toxopeus Serge
Published: August 2020

The independence of numerical and parameter uncertainties is investigated for the flow around the KVLCC2 tanker at Re = 4.6 × 106 using the time-averaged RANS equations supplemented by the k–ω two-equation SST model. The uncertain input parameter is the inlet velocity that varies ±0.25% and ±0.50% for the determination of sensitivity coefficients using finite-difference approximations. The quantities of interest are the friction and pressure coefficients of the ship and the Cartesian velocity components and turbulence kinetic energy at the propeller plane.

A grid refinement study is performed for the nominal conditions to allow the estimation of the discretization error with power series expansions. However, for grids between 6 × 106 and 47.6 × 106 cells, not all the selected quantities of interest exhibit monotonic convergence. Therefore, the estimates of the sensitivity coefficients of the selected quantities of interest using the local sensitivity method and finite-differences performed for refinement levels that correspond to 0.764 × 106, 6 × 106 and 47.6 × 106 cells lead to significantly different values. Nonetheless, for a given grid, negligible differences are obtained for the sensitivity coefficients obtained with two different intervals in the finite-differences approximation.

Discrepancies between sensitivity coefficients are compared with the estimated numerical uncertainties. Results obtained in the study suggest that uncertainty quantification performed in coarse grids may be significantly affected by discretization errors.
Rotational resonances in the H
2
CO roaming reaction are revealed by detailed correlations
Authors: Quinn Mitchell S. , Nauta Klaas , Jordan Meredith J. T. , Bowman Joel M. , Houston Paul L. , Kable Scott H.
Published: August 2020

Duality of roaming mechanism in H
2
CO

The phenomenon of roaming in chemical reactions (that is, bypassing the minimum energy pathway from unlikely geometries) has attracted a great deal of attention in the chemical reaction dynamics community over the past decade and still demonstrates unexpected results. Using velocity-map imaging of state-selected H
2
products of H
2
CO photodissociation, Quinn
et al.
discovered the bimodal structure of rotational distribution of the other product fragment, CO. Quasiclassical trajectories showed that this bimodality originates from two distinctive reaction pathways that proceed by the trans or cis configuration of O–C–H⋯H, leading to high or low rotational excitations of CO, respectively. Whether such a mechanism is present in the many other chemical reactions for which roaming reaction pathways have been reported is yet to be determined.

Science
, this issue p.
1592
Cohesion of Sister Chromosome Termini during the Early Stages of Sporulation in Bacillus subtilis
Authors: Willis Clare , Errington Jeff , Wu Ling Juan
Published: August 2020

Endospore formation in
Firmicutes
bacteria provides one of the most highly resistant life forms on earth. During the early stages of endospore formation, the cell cycle is reorganized so that exactly two fully replicated chromosomes are generated, before the cell divides asymmetrically to generate the prespore and mother cell compartments that are critical for the developmental process. Decades ago, it was discovered that just prior to asymmetrical division the two chromosomes enter an unusual elongated configuration called the axial filament. This paper provides new insights into the nature of the axial filament structure and suggests that cohesion of the normally separated sister chromosome termini plays an important role in axial filament formation.
Association between non-alcoholic fatty liver disease-associated hepatic fibrosis and bone mineral density in postmenopausal women with type 2 diabetes or impaired glucose regulation
Authors: Zhu Xiaopeng , Yan Hongmei , Chang Xinxia , Xia Mingfeng , Zhang Linshan , Wang Liu , Sun Xiaoyang , Yang Xinyu , Gao Xin , Bian Hua
Published: August 2020

Introduction

To evaluate the association of non-alcoholic fatty liver disease (NAFLD)-associated hepatic fibrosis with bone mineral density (BMD) in postmenopausal women with type 2 diabetes mellitus (T2DM) or impaired glucose regulation (IGR).

Research design and methods

Two cohorts including 46 subjects with biopsy-proven NAFLD and 445 subjects with proton magnetic resonance spectrum-proven NAFLD were enrolled in this study. All subjects were postmenopausal women with T2DM or IGR. BMD at the lumbar spine L1–L4 and hip was measured using dual-energy X-ray absorptiometry. NAFLD fibrosis stage and NAFLD fibrosis score were used to evaluate the severity of liver fibrosis.

Results

In subjects with liver biopsy-proven NAFLD, BMD (T-score, Z-score and BMD value) in the advanced fibrosis group were significantly lower than that in the non-advanced fibrosis group (p<0.05). Fibrosis stage was negatively associated with T-score, Z-score and BMD value after adjusting for age, body mass index (BMI) and fasting plasma glucose (FPG). Additionally, fibrosis stage was independently associated with T-score, Z-score and BMD value after adjusting for age, BMI and FPG. These results were validated in a large cohort of 445 subjects. Additionally, bone metabolism-associated factors, including calcium and phosphate, were associated with liver fibrosis, indicating that bone metabolism may play a critical role in the association between liver fibrosis and BMD. Mechanically, parathyroid hormone and biomarkers of bone formation (osteocalcin and procollagen type 1 N-terminal propeptide) and bone resorption (procollagen type I carboxy terminal peptide β special sequence) were increased in subjects with advanced liver fibrosis than in subjects without advanced liver fibrosis, indicating that liver fibrosis decreased BMD probably via increasing bone turnover.

Conclusions

NAFLD-associated hepatic fibrosis was negatively associated with decreased BMD in postmenopausal women with T2DM or IGR. Liver fibrosis decreased BMD probably via increasing bone turnover. Severe liver fibrosis may represent high risk for osteoporosis in postmenopausal women with T2DM or IGR.
Was amorphous aluminium hydroxyphosphate sulfate adequately evaluated before authorisation in Europe?
Authors: Petersen Sesilje B , Gluud Christian
Published: August 2020

The Merck Sharp & Dohme Corp aluminium adjuvant ‘amorphous aluminium hydroxyphosphate sulfate’ (AAHS), primarily used in the Gardasil vaccines against human papilloma virus, has been criticised for lack of evidence for its safety. Documentation from Danish authorities and answers from the European Medicines Agency (EMA) suggest that AAHS may not have been sufficiently evaluated. Documentation from the Danish Medicines Agency shows discrepancies in the trial documents of two prelicensure clinical trials with Gardasil in 2002 and 2003. For both trials, the Agency seems to have authorised potassium aluminium sulfate as the adjuvant and not AAHS. In addition, the participants in the trial launched in 2002 were informed that the comparator was saline, even though the comparator was AAHS in an expedient consisting of L-histidine, polysorbate-80, sodium borate and sodium chloride. According to the EMA, AAHS was first introduced in Europe in 2004 as the adjuvant in Procomvax, a vaccine against the hepatitis B virus andHaemophilus influenzatype b. The EMA reports that AAHS was introduced without any prelicensure safety evaluation. The adjuvant is described by the company to be both physically and functionally distinct from all other previously used aluminium adjuvants. There is a need for rigorous evaluation of benefits and harms of the adjuvant AAHS.
Estimating the proportion of overweight soldiers in the Australian Army by combat uniform waist size
Authors: Selman Jason , Zevenbergen M , Wing G
Published: August 2020

Introduction

Recent studies have shown an increasing number of overweight and obese members serving in many armies. Overweight and obesity can be estimated using either body mass index or waist circumference measures. The aim of this research was to estimate the proportion of the Australian Army considered to be overweight and obese by waist circumference using the proxy measure of issued combat uniform waist size.

Method

The Australian Army has been progressively replacing combat uniforms with a new uniform design and camouflage pattern since 2016. The total number of issued combat uniforms by size was obtained from the points of issue for the three Australian Army combat brigades from the first issue of the new uniform in January 2016 through to November 2019. The waist size of issued combat pants was collated from each of the three points of issue, adjusted for measured waist size accuracy and sex, and analysed to estimate the proportion of overweight and obese soldiers in the Australian Army.

Results

There were a total of 155 735 combat pants issued across the three points of issue. The mean waist size based on combat uniform pant size was found to be 90.4 cm, with an SD of 7.5 cm. Based on these data, approximately 23.3% of the Australian Army population can be estimated to be overweight and an additional 4.5% to be obese.

Conclusions

The Australian Army, like many western armies, has a significant proportion of overweight personnel. This can negatively affect operational capability, health and future healthcare costs both within the military and to society after military service has concluded. This is the first study to use a uniform waist size as a proxy to estimate overweight and obesity. This technique has application for the military, emergency services or any other organisation in which uniforms are provided.
Prevalence and temporal trends of presarcopenia metrics and related body composition measurements from the 1999 to 2006 NHANES
Authors: Li Ji-Bin , Wu Yuwan , Gu Dantong , Li Huajun , Zhang Xi
Published: August 2020

Objective

To evaluate the prevalence and temporal trends of presarcopenia and related body composition measurements.

Design

Cross-sectional study.

Setting

National Health and Nutrition Examination Survey (NHANES) 1999–2006.

Methods

Presarcopenia was defined according to the guidelines from the European Working Group on Sarcopenia. Logistic or linear regression models were used to evaluate the linear trend of the prevalence of presarcopenia, obesity and related body composition measurements.

Participants

A total of 29 947 participants aged 18–90 years from five waves of the NHANES were included in the analysis.

Outcome measures

Presarcopenia was sex-specifically defined as having a skeletal mass index ≤7.26 kg/m2 in men and ≤5.5 kg/m2 in women. Body composition measurements, including total body fat percentage, total body fat mass, total lean body mass, appendicular skeletal muscle mass and bone mineral density, were obtained by dual-energy X-ray absorptiometry.

Results

The overall prevalence of presarcopenia ranged from 16.4% in 1999–2000 to 14.8% in 2005–2006 (p for trend=0.78). Presarcopenia was stable in both males (p for trend=0.36) and females (p for trend=0.20). The presarcopenia prevalence was significantly elevated among the age group of 18–39 years old (from 11.3% to 14.1%, p for trend=0.04) and among non-Hispanic blacks (p for trend <0.001). Adults aged ≥80 years old had the highest prevalence.

Conclusions

The prevalence of presarcopenia increased among young individuals over time. Non-Hispanic blacks also demonstrated an increasing trend in the prevalence over time.
Efficacy of biofeedback, repetitive transcranial magnetic stimulation and pelvic floor muscle training for female neurogenic bladder dysfunction after spinal cord injury: a study protocol for a randomised controlled trial
Authors: Xu Lin , Fu Chenying , Zhang Qing , Xiong Feng , Peng Lihong , Liang Zejun , Chen Li , He Chengqi , Wei Quan
Published: August 2020

Introduction

Neurogenic bladder dysfunction is prevalent in female patients with spinal cord injury (SCI), and previous guidelines have recommended pelvic floor muscle training (PFMT) for first-line conservative treatment. However, the actual regimen of PFMT varies widely and the single treatment does not satisfy the need of some patients. Therefore, this study aims to provide a detailed rationale and methodology for comparing the effectiveness of PFMT, biofeedback and repetitive transcranial magnetic stimulation (rTMS) as adjunct treatments for neurogenic bladder dysfunction.

Methods and analysis

This trial is a single-centre randomised controlled trial for female patients with urinary incontinence (UI) in phase of chronic SCI. Eligible participants will be randomised to one of four arms: (1) PFMT, (2) PFMT with biofeedback, (3) PFMT and rTMS and (4) PFMT with biofeedback and rTMS. There will be 44 participants in each arm and all the subjects will undergo 20 treatment sessions, five times a week for 4 weeks. The outcomes will be evaluated at 4 weeks, 3 months and 6 months after randomisation. The primary outcome is the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form, and the secondary outcomes include bladder diary, pelvic floor muscle function and the International Spinal Cord Injury Quality of Life Basic Data Set.

Ethics and dissemination

The Clinical Research and Biomedical Ethics Committee of the West China Hospital, Sichuan University has approved this trial and the approval number is 2019-885. All participants will be provided written informed consent after verification of the eligibility criteria. The results of this study will be accessible in peer-reviewed publications and be presented at academic conferences.

Trial registration number

Chinese Clinical Trial Registry (ChiCTR1900026126).
Incidence and risk factors of retinopathy of prematurity in Korle-Bu Teaching Hospital: a baseline prospective study
Authors: Braimah Imoro Zeba , Enweronu-Laryea Christabel , Sackey Adziri Harold , Kenu Ernest , Agyabeng Kofi , Ofori-Adjei Imelda-Odille Dziffa-Bella , Beyuo Vera , Oku Aaron , Essuman Vera Adobea
Published: August 2020

Objective

To determine the incidence of retinopathy of prematurity (ROP) and any associated risk factors among preterm infants at the Neonatal Intensive Care Unit (NICU) of Korle-Bu Teaching Hospital (KBTH).

Design

Prospective study.

Setting

Level 3 NICU of KBTH from June 2018 to February 2019.

Participants

Eligible infants with birth weight (BW) less than 2 kg or gestational age (GA) less than 37 weeks were examined at scheduled intervals until full maturity of their retina.

Outcome measures

The primary outcome measure was cumulative incidence of ROP and secondary outcome measure was risk factors associated with ROP.

Results

Of the 401 infants, 222 were females (55.4%), mean±SD GA was 32.3±2.4 weeks (median 32, IQR 31 to 34) and mean BW 1.6±0.4 kg (median 1.5, IQR 1.3 to 1.9). The cumulative incidence of ROP was 13.7% (95% CI: 10.5 to 17.5%), with 1.8% (seven infants) having type 1 ROP. Increased risk of ROP was observed in babies with supplemental oxygen exposure (p<0.001), BW less than 1.5 kg (p=0.019), confirmed neonatal sepsis (p=0.001), nasogastric tube feeding (p=0.03) and poor pupillary dilation (0.032). A reduced risk of ROP was observed in boys (p=0.004) and after delivery by caesarean section (p=0.019).

Conclusion

The rates of ROP at KBTH are comparable to other NICUs in sub-Saharan Africa. Birth weight less than 1.5 kg, confirmed neonatal sepsis, nasogastric tube feeding and poor pupil dilation were independently associated with increased incidence of ROP. ROP screening should be a part of the routine service for premature infants in Ghana.
Amyotrophic lateral sclerosis and the innate immune system: protocol for establishing a biobank and statistical analysis plan
Authors: Kjældgaard Anne-Lene , Pilely Katrine , Olsen Karsten Skovgaard , Lauritsen Anne Øberg , Pedersen Stephen Wørlich , Møller Kirsten , Garred Peter
Published: August 2020

Introduction

Amyotrophic lateral sclerosis (ALS) is a devastating, progressive disease that causes degeneration of the motor neurons leading to paresis of the bulbar and the skeletal musculature. The pathogenesis of ALS remains unknown. We will test the hypothesis that the complement system is involved in the pathophysiology of ALS. This protocol article describes our efforts to establish a national Danish ALS biobank. The primary aim is to obtain biological material from patients with ALS for the current study as well as for future studies.

Methods and analysis

We intend to establish an observational ALS biobank; some of the material from this biobank will be used for a prospective, observational case–control study. The participants are patients with ALS, neurologically healthy controls and non-ALS neurological controls. Each participant consents to be interviewed and to donate blood and cerebrospinal fluid to the biobank. Analysis of the complement system will be carried out on the three groups of patients and compared.

Ethics and dissemination

The project has been approved by the Committees on Health Research Ethics in the Capital Region of Denmark (Approval number H-16017145) and the Danish Data Protection Agency (file number 2012-58-0004). All results will be published in peer-reviewed, medical journals and presented at scientific conferences.

Trial registration number

NCT02869048
Combining BRAF inhibition with oncolytic herpes simplex virus enhances the immune-mediated antitumor therapy of BRAF-mutant thyroid cancer
Authors: Crespo-Rodriguez Eva , Bergerhoff Katharina , Bozhanova Galabina , Foo Shane , Patin Emmanuel C , Whittock Harriet , Buus Richard , Haider Syed , Muirhead Gareth , Thway Khin , Newbold Kate , Coffin Robert S , Vile Richard G , Kim Dae , McLaughlin Martin , Melcher Alan A , Harrington Kevin J , Pedersen Malin
Published: August 2020

Background

The aggressive clinical behavior of poorly differentiated and anaplastic thyroid cancers (PDTC and ATC) has proven challenging to treat, and survival beyond a few months from diagnosis is rare. Although 30%–60% of these tumors contain mutations in the BRAF gene, inhibitors designed specifically to target oncogenic BRAF have shown limited and only short-lasting therapeutic benefits as single agents, thus highlighting the need for improved treatment strategies, including novel combinations.

Methods

Using a BRAFV600E-driven mouse model of ATC, we investigated the therapeutic efficacy of the combination of BRAF inhibition and oncolytic herpes simplex virus (oHSV). Analyses of samples from tumor-bearing mice were performed to immunologically characterize the effects of different treatments. These immune data were used to inform the incorporation of immune checkpoint inhibitors into triple combination therapies.

Results

We characterized the immune landscape in vivo following BRAF inhibitor treatment and detected only modest immune changes. We, therefore, hypothesized that the addition of oncolytic virotherapy to BRAF inhibition in thyroid cancer would create a more favorable tumor immune microenvironment, boost the inflammatory status of tumors and improve BRAF inhibitor therapy. First, we showed that thyroid cancer cells were susceptible to infection with oHSV and that this process was associated with activation of the immune tumor microenvironment in vivo. Next, we showed improved therapeutic responses when combining oHSV and BRAF inhibition in vivo, although no synergistic effects were seen in vitro, further confirming that the dominant effect of oHSV in this context was likely immune-mediated. Importantly, both gene and protein expression data revealed an increase in activation of T cells and natural killer (NK) cells in the tumor in combination-treated samples. The benefit of combination oHSV and BRAF inhibitor therapy was abrogated when T cells or NK cells were depleted in vivo. In addition, we showed upregulation of PD-L1 and CTLA-4 following combined treatment and demonstrated that blockade of the PD-1/PD-L1 axis or CTLA-4 further improved combination therapy.

Conclusions

The combination of oHSV and BRAF inhibition significantly improved survival in a mouse model of ATC by enhancing immune-mediated antitumor effects, and triple combination therapies, including either PD-1 or CTLA-4 blockade, further improved therapy.
Melatonin modulates acute cardiac muscle damage induced by carbon tetrachloride — involvement of oxidative damage, glutathione, and arginine and nitric oxide metabolism
Authors: Ćirić Zdravković Snezana , Kostić Tomislav , Marcetić Zoran P. , Šulović Ljiljana S. , Nedeljković Biserka M. , Preljević Adem , Toskić Dragan , Sokolović Dušan
Published: August 2020

The present study was designed to evaluate the cardioprotective effects of melatonin (a single dose of 50 mg·kg–1), a naturally occurring polypharmacological molecule, in Wistar rats acutely exposed to carbon tetrachloride (CCl4). This was done for the first time by tracking different biochemical parameters that reflect rat heart antioxidative and oxidative capacities, nitric oxide and arginine metabolism, and the glutathione cycle. Additionally, the extrinsic apoptosis pathway related parameters were studied. Acute exposure to CCl4led to an increase in the studied tissue oxidant parameters (hydrogen peroxide, malondialdehyde, and carbonylated protein content), as well as the activity alteration of antioxidant (catalase, superoxide dismutase, and peroxidase) and glutathione-metabolizing (glutathione peroxidase, S-transferase, and reductase) enzymes. Furthermore, CCl4caused a disturbance in the tissue myeloperoxidase, nitric oxide, citrulline, arginase, and inducible nitric oxide synthase content and activities and in two apoptosis-related parameters, caspase-3 and FAS ligand. Melatonin as a post-treatment prevented the changes induced by CCl4to a differing extent, and in some cases, it was so potent that it completely abolished any tissue disturbances. This study is a promising starting point for further research directed to the development of melatonin treatment in cardiac tissue associated diseases.
Permanent magnetic brushless DC motor magnetism performance depends on different intelligent controller response
Authors: Hsu Chang-Hung , Chang Chia-Wei
Published: August 2020

This paper presents an intelligent controller to improve the performance of a permanent magnetic brushless DC motor (PM-BLDCM) in a ball-and-beam system (BBS). A hybrid interval type-2 fuzzy sliding controller (HFSC) was designed and compared with a conventional extended Karnik–Mendel (EKM)-type controller. The performance of the intelligent controller can affect the control phase margin condition, which regulates the DC motor rotational flux directly due to factors of voltage and current. Based on this result, the flux distribution of the magnetic material of the BLDCM was investigated through finite element analysis (FEA). For the torque response, which is critical to the performance of the BBS, the proposed intelligent controller exhibited faster response than that achieved by a conventional approach. The computation efficiency of the developed controller was significantly enhanced, and the computing time was reduced by more than 90%. Simulation results show that the torque required to achieve a prescribed control action was reduced by more than 10%. These results validate the performance of the proposed controller.
Writing a Test Plan
Authors: Neville-Neil George
Published: August 2020

If you can think of each of your tests as an experiment with a hypothesis, a test methodology, and a test result, it should all fall into place rather than falling through the cracks.
Dietary nitrate reduces blood pressure and cerebral artery velocity fluctuations and improves cerebral autoregulation in transient ischemic attack patients
Authors: Fan Jui-Lin , O’Donnell Terrence , Lanford Jeremy , Croft Kevin , Watson Eloise , Smyth Duncan , Koch Henrietta , Wong Lai-Kin , Tzeng Yu-Chieh
Published: August 2020

We found dietary nitrate supplementation reduced blood pressure and brain blood flow fluctuations and improved the relationship between blood pressure and brain blood flow in transient ischemic attack patients. Meanwhile, dietary nitrate had no effects on the brain blood vessels’ response to CO2. We attribute the improved brain blood flow stability to the improved myogenic control of blood pressure with dietary nitrate. Our findings indicate that dietary nitrate could be an effective strategy for stabilizing blood pressure and brain blood flow following transient ischemic attack.
Evolution Dynamics of Agricultural Internet of Things Technology Promotion and Adoption in China
Authors: Wu Fang , Ma Junhai
Published: August 2020

Internet of Things is the core technology of smart agriculture and can reform and upgrade traditional agriculture for reducing cost, reducing pollution, and increasing productivity and quality in China. From government-led and market economy perspectives, promotion mechanisms and sustainable adoption of agricultural Internet of Things technology are analyzed. In the initial application phase, the promotion of Internet of Things requires government support. For investigating the relationship between the government and farmers, this study builds an evolutionary game model and finds that increases of cost subsidy, farmers’ negative feedback, government’s positive feedback, and chemical agriculture cost can make the model evolve toward the strategy set: farmer adoption and government support. For long-term development, a sustainable model in competitive market is built by competition game and exponential replication equation. This paper analyzes the equilibrium of adoption ratio, long-run profit, and the conversion between equilibrium points under capacity sharing strategy in competitive market. It is also found that the market will eventually evolve to the technology selection strategy whose long-run average profit dominates the market. The innovations are that evolutionary game is used for analyzing the initial stage and competitive game and asynchronous update mechanism are used for analyzing the sustainable development adoption. At last, references are provided for agricultural Internet of Things development policy from the perspectives of initial promotion and long-run sustainability.
The Canine Erythrocyte Sedimentation Rate (ESR): Evaluation of a Point-of-Care Testing Device (MINIPET DIESSE)
Authors: Militello Carlo , Pasquini Anna , Medina Valentin Anyela Andrea , Simčič Petra , De Feo Giulia , Lubas George
Published: August 2020

The erythrocyte sedimentation rate (ESR) in canine medicine has been replaced by the evaluation of a few sensitive markers of the acute-phase proteins. The aim of the study was to evaluate the ESR using a point-of-care (MINIPET, DIESSE Diagnostica Senese S.p.A.) device (ESR-MP) and to compare the results with the gold standard Westergren method (ESR-W) in dogs. One hundred and nineteen K3-EDTA blood samples for complete blood count were randomly selected and assayed for ESR. The reference interval (RI) was established using the percentile method. The coefficient of variation (CV) in intra-assay and interassay precision of ESR-MP was calculated. The analytical sensitivity (Se), specificity (Sp), positive predictive values (PPVs), and negative predictive values (NPVs) were calculated. Agreement between ESR-MP and ESR-W was assessed with Pearson correlation coefficient (r), Cohen concordance test (K), Passing-Bablok regression, and Bland–Altman plots. Ten canine samples (8.4%) were ruled out because of flag-error by the MINIPET instrument (4.2%) or because they showed the diphasic pattern in ESR-W (4.2%). The canine RI of ESR-MP was 0–10 mm/h. Precision was excellent in intra-assay (CV = 0.02) and interassay (CV = 0.32). The analytical characteristics of ESR-MP in nonanemic samples were as follows: Se = 0.82, Sp = 0.95, PPV = 0.82, and NPV = 0.95. The accuracy of ESR-MP was better than ESR-W in nonanemic samples (r = 0.87; K = 0.77) and lower in anemic subjects (Hct <37%) (r = 0.76; K = 0.69). The Passing-Bablok regression showed the presence of systematic error and the absence of proportional error only in nonanemic blood samples. The Bland–Altman plots gave negative average values due to the difference in RIs and an agreement in both ESRs. The ESR-MP results can be obtained with the same K3-EDTA tubes used for the blood count, in shortcut time, and at reduced costs using the MINIPET device. These investigations highlight that ESR-MP could be useful in canine clinical settings.
Role of Nrf2 and Its Activators in Cardiocerebral Vascular Disease
Authors: Cheng Liangkai , Zhang Hong , Wu Fang , Liu Zhongqiu , Cheng Yuanyuan , Wang Caiyan
Published: August 2020

Cardiocerebral vascular disease (CCVD) is a common disease with high morbidity, disability, and mortality. Oxidative stress (OS) is closely related to the progression of CCVD. Abnormal redox regulation leads to OS and overproduction of reactive oxygen species (ROS), which can cause biomolecular and cellular damage. The Nrf2/antioxidant response element (ARE) signaling pathway is one of the most important defense systems against exogenous and endogenous OS injury, and Nrf2 is regarded as a vital pharmacological target. The complexity of the CCVD pathological process and the current difficulties in conducting clinical trials have hindered the development of therapeutic drugs. Furthermore, little is known about the role of the Nrf2/ARE signaling pathway in CCVD. Clarifying the role of the Nrf2/ARE signaling pathway in CCVD can provide new ideas for drug design. This review details the recent advancements in the regulation of the Nrf2/ARE system and its role and activators in common CCVD development.
Prevalence and Factors Associated with Depression among HIV/AIDS-Infected Patients Attending ART Clinic at Jimma University Medical Center, Jimma, Southwest Ethiopia
Authors: Dorsisa Beyene , Ahimed Gutema , Anand Susan , Bekela Tariku
Published: August 2020

Background. HIV is a chronic life-threatening illness and, like other similar chronic and stigmatizing illnesses, can be stressful to manage. Depression is a common mental health problem that deteriorates the quality of life of people with HIV/AIDS and found to be a strong predictor for noncompliance to antiretroviral therapy treatment. Therefore, epidemiological evidence on the factors associated with depression among patients with HIV/AIDS can contribute towards effective and efficient preventive health care strategies for this population. Objectives. To assess the prevalence and factors associated with depression among HIV/AIDS-infected patients attending ART clinic at Jimma University Medical Center, Jimma, Southwest Ethiopia, in 2018. Methods. This study followed an institution-based cross-sectional quantitative study design. A simple random sampling method yielded 303 participants who were interviewed from April to May 2018, using a pretested questionnaire, followed by their card review. The SPSS version 23 was used for bivariate analysis which was used to find out the significance of association. Variables that showed association in bivariate analysis at p value < 0.25 were entered to multivariable logistic regressions to control for confounders, and the significance of association was determined by 95% confidence interval and p value < 0.05. Results. The point prevalence of depression was 94 (31%). Variables like sex (AOR=0.510 (95%CI=0.264‐0.986)), marital status (AOR=3.610 (95%CI=1.649‐7.901)), opportunistic infection (AOR=3.122 (95%CI=1.700‐5.733)), and medication adherence (AOR=0.470 (95%CI=0.266‐0.831)) were significantly associated with depression. Conclusion and Recommendation. From the findings of this study, it is possible to conclude that depression was highly prevalent among people living with HIV/ADS. Sex, marital status, opportunistic infection, and medication adherence were found to be associated with depression and need attention from the health professional working in the ART clinic.
The Application of Single-Cell RNA Sequencing in Vaccinology
Authors: Noé Andrés , Cargill Tamsin N. , Nielsen Carolyn M. , Russell Andrew J. C. , Barnes Eleanor
Published: August 2020

Single-cell RNA sequencing allows highly detailed profiling of cellular immune responses from limited-volume samples, advancing prospects of a new era of systems immunology. The power of single-cell RNA sequencing offers various opportunities to decipher the immune response to infectious diseases and vaccines. Here, we describe the potential uses of single-cell RNA sequencing methods in prophylactic vaccine development, concentrating on infectious diseases including COVID-19. Using examples from several diseases, we review how single-cell RNA sequencing has been used to evaluate the immunological response to different vaccine platforms and regimens. By highlighting published and unpublished single-cell RNA sequencing studies relevant to vaccinology, we discuss some general considerations how the field could be enriched with the widespread adoption of this technology.
Travel Time Prediction Model of Freeway Corridor Based on Real-Time Safety Reliability
Authors: Yuan Huazhi , Huang Zhaoguo , Zhang Hongying
Published: August 2020

By considering the feature of vehicle driving on the event management unit of the freeway corridor, according to the system target, a method to divide the management unit of the road network was put forward. The relative safety braking deceleration was taken as the evaluation index of single-vehicle driving risk. The reliability graph relationship and structure-function between the management unit and subunit were analyzed. Then, dynamic safety reliability and real-time safety reliability were determined on the basis of driving risk. In addition, the queuing and dissipating characteristics of the management unit under traffic incidents were analyzed based on the wave theory. The incident duration and dissipation time were also calculated. At the same time, the travel time prediction model of the incident management unit was set up when the real-time safety reliability was taken as a road resistance function. Finally, an improved travel time prediction model established in this paper is of great significance to improve traffic safety and efficiency, and the research results will provide an important theoretical foundation in the freeway corridor route decision.
Current Status of Alginate in Drug Delivery
Authors: Hariyadi Dewi Melani , Islam Nazrul
Published: August 2020

Alginate is one of the natural polymers that are often used in drug- and protein-delivery systems. The use of alginate can provide several advantages including ease of preparation, biocompatibility, biodegradability, and nontoxicity. It can be applied to various routes of drug administration including targeted or localized drug-delivery systems. The development of alginates as a selected polymer in various delivery systems can be adjusted depending on the challenges that must be overcome by drug or proteins or the system itself. The increased effectiveness and safety of sodium alginate in the drug- or protein-delivery system are evidenced by changing the physicochemical characteristics of the drug or proteins. In this review, various routes of alginate-based drug or protein delivery, the effectivity of alginate in the stem cells, and cell encapsulation have been discussed. The recent advances in the in vivo alginate-based drug-delivery systems as well as their toxicities have also been reviewed.