bluuebunny/crossref_metadata_2025 huggingface dataset:
Transient prediction capabilities of a novel physics-based ignition delay model in multi-pulsed direct injection diesel engines
Authors: Samuel J Jensen , Ramesh A
Published: August 2019

This work is an extension of a novel physics-based ignition delay modeling methodology previously developed by the authors to predict physical and chemical ignition delays of multiple injections during steady operations in diesel engines. The modeling methodology is refined in this work to consider the influence of additional operating parameters such as volumetric efficiency, exhaust temperature and pressure on the ignition delay of multiple injections. Computational fluid dynamics predictions on two different engines indicated that the main spray encounters local temperatures about 60 K above average temperatures for about 1 mg of pilot. Hence, the modeling methodology was further refined to include this effect by considering the air mass trapped in pilot spray, computed based on the spray penetration and cone angle and tuned using results of the computational fluid dynamics studies. Comparisons of the ignition delay predictions with the stock boost temperature sensor and a specially incorporated, transient-capable fine wire thermocouple indicated that the measurements with stock sensor could be satisfactorily used for transients. Cycle-by-cycle changes in ignition delay could be predicted accurately when transients were imposed in boost pressure, rail pressure and main injection quantity in a turbocharged intercooled diesel engine controlled with an open engine control unit. Further validations were done even under a transient cycle when the engine was controlled by its stock engine control unit. The same tuning constants could be used for the prediction of the ignition delay under transients on another naturally aspirated engine. This indicates the suitability of the model for application in different engines. Finally, the model was incorporated within an open engine controller, and cycle-by-cycle prediction of ignition delays of the pilot and main injections were done in real time. It was possible to compute the ignition delays in less than 2 ms within engine control unit using the already available sensor inputs within an error band of ±60 µs.
Effect of the use of a thermoelectric generator on the pumping work of a diesel engine
Authors: Ezzitouni Samir , Fernández-Yáñez Pablo , Sánchez Luis , Armas Octavio , Soto Felipe
Published: August 2019

Approximately a third part of the energy intake of a light-duty diesel engine is wasted through the exhaust system. Rising awareness of environmental issues together with fuel economy has encouraged research upon energy recovery in internal combustion engines. This article focuses on the application of thermoelectric generators in light-duty diesel vehicles. Most studies available in the literature tend to focus on maximizing the recovered electrical power, not always considering the increase in engine pumping work or testing conditions similar to those of a vehicle. The goal of this article is to evaluate the consequences of the modification of the cross-sectional area in the exhaust pipe that adding a thermoelectric generator implies and to compare them with the electrical power produced by the thermoelectric generator. The effect on the indicated and pumping parameters of the engine under common urban driving conditions is presented. From the results, it can be drawn that within the limits of engine speed and torque tested, the modification of the cross-sectional area does not have a significant negative effect on the engine pumping efficiency. This means that there is potential for the employment of this technique in energy recovery from light-duty vehicles.
Nozzle tip wetting in gasoline direct injection injector and its link with nozzle internal flow
Authors: Huang Weidi , Moon Seoksu , Wang Jin , Murayama Kei , Arima Toshiyuki , Sasaki Yuzuru , Arioka Akira
Published: August 2019

Fuel film in the gasoline direct injection injector tip, or so-called nozzle tip wetting, has been found to be an important contributor of particle emissions. Attempts have been made to reduce the nozzle tip wetting by optimizing nozzle geometry designs. However, the inherent mechanism of the nozzle tip wetting formation and its link with nozzle internal flow is still unclear yet due to the lack of direct observations. To overcome this insufficiency, the nozzle internal flow and the formation process of the nozzle tip wetting were visualized in the real-scale aluminum nozzles using the X-ray phase-contrast technique. Results showed that the needle bouncing, injection pressure, and hole configuration affect the formation of the nozzle tip wetting, while the influence of needle bouncing is the most critical. A further study was conducted to examine the effect of nozzle counterbore diameter on the nozzle tip wetting. It was found that with an increase in counterbore diameter, the nozzle tip wetting slightly increased first and then decreased sharply after the counterbore diameter exceeded 0.40 mm. The mechanisms of the aforementioned phenomena were discussed in detail, which can contribute to the better understandings and control strategies of nozzle tip wetting.
Hydrodynamic luminescence in a model diesel injector return valve
Authors: Lockett Russell D , Bonifacio Alberto
Published: August 2019

A sample of unadditized diesel fuel was passed through an optically accessible model diesel injector return valve, which consisted of two successive nozzles connected to an intermediate fuel gallery. The first nozzle was cylindrical, while the second nozzle was stepped. The fuel was observed to produce a multi-phase, cavitating flow and a luminous blue-violet emission at the entrance to the second nozzle hole. The flow in the upstream intermediate fuel gallery and the first nozzle hole remained single-phase. Spectral analysis of the luminous emission revealed a spectrum with thermal features containing broad spectral lines and peaks at 358, 389, 405, 412, 430 and 475 nm, suggesting that the emission was dominated by π*→π transitions in the alkylated mono-, di-, and tri-aromatics, with additional spectral contributions from CH, C2, C3 and hydrogen (H).
Bioactive Immunomodulatory Compounds: A Novel Combinatorial Strategy for Integrated Medicine in Oncology? BAIC Exposure in Cancer Cells
Authors: Corradetti Bruna , Vaiasicca Salvatore , Mantovani Mauro , Virgili Edy , Bonucci Massimo , Hammarberg Ferri Ivano
Published: August 2019

The Standardized Cultured Extract of Lentinula edodes Mycelia (also known as Active Hexose Correlated Compound, AHCC) and Wasabia japonica (Wasabi) are natural nutritional supplements known for their immunomodulatory and anticancer potential. The aim of this study was to evaluate the combinatorial effect of the bioactive immunomodulatory compound (BAIC), obtained by combining Wasabi and AHCC, on human breast (MCF-7) and pancreatic (Panc02) adenocarcinoma cell lines. Data obtained revealed that BAIC determines a striking decline in cancer cell growth at minimal concentrations compared with the use of Wasabi and AHCC as single agents. A significant increase in the G0/G1 subpopulation together with a marked augmentation in the percentage of apoptotic cells was demonstrated by flow cytometry, together with a significant upregulation in the expression of genes associated to the apoptotic cascade in both cell lines. The inhibitory role BAIC plays in mammospheres formation from MCF-7-derived cancer stem cells was shown with a marked reduction in size and number. Interestingly, when BAIC was exposed to monocytic cells, no cytotoxic effects were observed. A monocytes-to-macrophages differentiation was rather observed with the concomitant acquisition of an anti-inflammatory phenotype. Taken together, our findings suggest that BAIC could be used as a potential integration of standard chemotherapy treatments because of the improved inhibitory activity on cancer cell proliferation and reduced potential adverse effects.
Hypoalbuminemia Predicts Increased Readmission and Emergency Department Visits After Lower Extremity Bypass
Authors: Westfall John C. , Cheng Thomas W. , Farber Alik , Jones Douglas W. , Eslami Mohammad H. , Kalish Jeffrey A. , Rybin Denis , Siracuse Jeffrey J.
Published: August 2019

Introduction:

Preoperative hypoalbuminemia is associated with poor outcomes across many surgical fields. However, the effects on outcomes after lower extremity bypass (LEB), particularly over the 90-day global surgical period, are unclear. Our goal was to analyze the effect of hypoalbuminemia within 90 days after LE bypass.

Methods:

We performed a single-center retrospective review of all infrainguinal LEBs from 2007 to 2017. Patients were categorized into 3 preoperative albumin groups: severe hypoalbuminemia (SH; albumin ≤2.8g/dL), mild–moderate hypoalbuminemia (MH; albumin >2.8-3.5g/dL), and normal albumin (albumin >3.5g/dL). Patient and procedural details were recorded. Outcomes analyzed included wound infection, myocardial infarction (MI), pulmonary complications, early graft occlusion (≤30 days), mortality, and emergency department (ED) presentation and readmissions within 30 and 90 days. Multivariable analysis was performed.

Results:

We identified 313 patients undergoing LEB—45 (14.4%) with SH, 133 (42.5%) with MH, and 135 (43.1%) with normal albumin. Overall, the mean age was 65.7 years, and 63.3% were male. The SH group more frequently had tissue loss, diabetes, hypertension, end-stage renal disease, preoperative hematocrit <30%, and patients admitted preoperatively (all P < .05). There were no significant differences in wound complications, MI, pulmonary complications, early graft occlusion, 30-day or 90-day mortality, and 30-day ED presentation. Severe hypoalbuminemia compared to MH and normal albumin, respectively, had significantly higher rates of 30-day readmission (40% vs 30.8% vs 17.8%, P = .005), 90-day ED presentation (55.6% vs 33.8% vs 29.6%, P = .006), and 90-day readmission (66.7% vs 48.9% vs 35.6%, P = .001). Multivariable analysis showed that SH was independently associated with 90-day ED presentation (odds ratio [OR]: 2.8, 95% confidence interval [CI]: 1.23-6.36, P = .014) and 90-day readmission (OR: 2.63, 95% CI: 1.21-5.71, P = .015).

Conclusion:

Our study suggests that patients with SH undergoing LEB had similar perioperative complication rates compared to normal albumin and MH groups, and SH was independently associated with 90-day ED presentation and readmission. Further studies are needed to assess other factors associated with ED visits and readmission.
Novel Application of Transcarotid Artery Stenting With Dynamic Flow Reversal for Treatment of Symptomatic Tandem Carotid Artery Lesions Via an Ascending Aorta to Common Carotid Artery Bypass Graft
Authors: Donde Nikunj N. , Wang S. Keisin , Liao Jane L. , Fajardo Andres C. , Hess Phillip , Motaganahalli Raghu L.
Published: August 2019

The treatment of patients with symptomatic tandem lesions of their carotid artery is challenging. One solution is carotid endarterectomy with retrograde ipsilateral proximal endovascular intervention, but it is associated with a higher postoperative risk of stroke. Unfortunately, symptomatic patients with tandem lesions often present with stenotic, calcified supra-aortic arch vessels and require multiple modalities to adequately revascularize including staged approaches or hybrid procedures. Herein, we report the successful treatment of a symptomatic 76-year-old female with a calcific severe stenosis of her innominate artery treated by a prosthetic bypass graft from her ascending aorta to proximal common carotid artery, interval ligation, and use of TransCarotid artery revascularization with reverse-flow to treat her proximal internal carotid artery stenosis via this bypass graft.
Internet of medical things for smart D3S to enable road safety
Authors: Ramzan Muhammad , Awan Shahid Mahmood , Aldabbas Hamza , Abid Adnan , Farhan Muhammad , Khalid Shehzad , Latif Rana M Amir
Published: August 2019

It has been seen that most of the accidents occur due to driver’s fatigue. Drowsiness is a state of mind before the driver falls asleep, which means the driver could not accomplish his actions, such as vehicular braking, controlling vehicular motion, properly. We have built an Internet of things–based medical application to analyze driver’s drowsiness. An architecture has been proposed and a simulation of that scenario in NS3 WSN simulation tool has been done. This simulation shows that the ratio of accidents can be majorly reduced. When drowsiness of drivers is captured, a message alert is delivered to all other drivers of the vehicles that are near to the sleeping driver; for this, different sensor nodes are used. Another unique feature of the sensor network used here is the collaborative effect of sensor nodes. So for measurement and analysis of applications on Google Play, a dataset of the medical applications category was scraped. The scraping was done with 550 applications of each category of medical applications. On each application on Google Play store, almost 70 attributes for each category were scraped. It is envisioned that, in future, wireless sensor networks will be an integral part of our lives, more so than the present-day personal computers.
Experimental investigations of wooden beam ends in masonry with interior insulation: Measured data in real-scale experimental walls exposed to semi-continental climatic conditions
Authors: Kopecký Pavel , Staněk Kamil , Bureš Michal , Richter Jan , Ryparová Pavla , Tywoniak Jan
Published: August 2019

This article deals with the hygrothermal performance of wooden beam ends embedded in brick masonry walls. The real-scale experiment involving three interior insulation systems with different water vapor resistances and different treatments of joist pockets was monitored for three consecutive years. The moisture load of test walls was controlled during the experiment. First, humidity of indoor air was increased in the cold season (2016–2017). Then, an artificial short-time intensive rain event brought liquid water onto the external surface of the test walls in July 2017. Despite relatively mild external climatic loads, relative humidity was unsatisfactorily high in unsealed joist pockets. Vapor and airtight sealing of the joist pockets improved the microclimate of the wooden beam ends. However, even in this case, relative humidity approached critical values for the onset of mold growth. The artificial rain load applied on the experimental walls noticeably worsened the hygrothermal conditions in the joist pockets. Relative humidity in the joist pockets further increased to a level where massive mold growth could be expected. Visual inspection of the wooden beam ends during reconstruction of the experiment, however, revealed only a small spot of mold on a single beam located in an unsealed joist pocket. Mold growth on samples of organic thermal insulation material was found by microscopic investigations. Molds were localized in small separated colonies. These in situ and laboratory investigations do not confirm the calculated values of mold growth index. In conclusion, sealing of wooden beam ends improved their hygrothermal performance in the experiment.
Synthesis of C-ring hydrogenated sinomenine cinnamate derivatives via Heck reactions
Authors: Pan Hongmei , Lu Tong , Wu Xuedan , Jiang Chuan , Gu Chengwen , Zhang Kehua , Jin Jie
Published: August 2019

The synthesis of C-ring hydrogenated sinomenine derivatives is accomplished from sinomenine by treatment with Zn-Hg/HCl, halogenation with NIS, and Heck reactions with various acrylates. A total of nine novel sinomenine cinnamate derivatives are obtained in 84%–93% yields. The structures of all the derivatives are characterized by 1H NMR, 13C NMR, and MS spectroscopy.
Preparation and adsorption properties of a facile solid cucurbit[8]uril-based porous supramolecular assembly
Authors: Chen Chunchun , Ge Weiwei , Chen Kai , Tao Zhu , Zhang Yunqian , Jiang Zhu Qian
Published: August 2019

Cucurbit[8]uril (Q[8]) was used as the building block for the facile preparation of Q[8]-based supramolecular assemblies in aqueous HCl solutions (A). The Q[8]-based supramolecular assembly was constructed of Q[8] molecules held together through outer surface interactions of cucurbit[ n]urils, and hydrogen bonding between latticed water molecules and portal carbonyl oxygens of Q[8]. The porous structure resulted in different adsorption properties for different fluorophore guests (FGs), including dyes and fused-ring compounds, and fluorescence enhancement or colour changes resulted in luminescent materials (FG@As). Moreover, some of the FG@A systems could selectively respond to certain volatile organic compounds, for which they can be used as solid sensors.
How can I get a renal access if I do not have an ultrasound and cannot opacify the collecting system? Another use of the hydrophilic guide wire
Authors: Serrano Adolfo , Bravo-Balado Alejandra , Díaz Ana María , Barco-Castillo Catalina , Trujillo Carlos Gustavo
Published: August 2019

It is well-known that fluoroscopic guidance is the most commonly used imaging technique for percutaneous access to the kidney. However, we might encounter difficulties when attempting to establish the limits of the collecting system for a percutaneous puncture, especially in places where the use of ultrasound guidance in the operating room is limited. We aim to describe the use of a hydrophilic guide wire to delimit the collecting system when this becomes difficult with conventional techniques.
Health information technology foresight for Iran: A Delphi study of experts’ views to inform future policymaking
Authors: Hemmat Morteza , Ayatollahi Haleh , Maleki Mohammadreza , Saghafi Fatemeh
Published: August 2019

Background:

Policymakers require a systematic approach when planning for information technology needs in healthcare.

Objective:

The aim of this study was to obtain experts’ predictions of future health information technology (HIT) needs until 2025 for Iran in relation to the relative importance of key technologies, expected timeframe of realisation, areas that may be impacted upon and obstacles to achieving these goals.

Method:

This article presents results from the third phase (a Delphi study) of a larger mixed-method study. Policymakers from the Iranian Ministry of Health and faculty members from different medical universities across the country who were expert in the field of HIT were invited to participate ( n = 61).

Results:

Participants (39) completed the first-round questionnaire and 24 completed the second. The development of personal health records ( n = 32, 82.0%), the development of clinical decision-making systems ( n = 30, 76.9%) and the use of business intelligence for collecting and analysing clinical and financial data ( n = 32, 82.0%) were predicted to occur after 2025. The healthcare areas predicted to experience the greatest impact from most HITs were facilitating patient–provider communication and improving healthcare quality. Key barriers to achieving HITs were related to weaknesses in planning and limited financial resources for most technologies.

Conclusion:

By identifying the areas of impact and the barriers to achieving the HIT goals, more accurate planning is possible and resources can be allocated according to priorities.
Sources of political parties’ campaign expenditure in Nigeria’s Fourth Republic: Examining the 2015 General Election
Authors: Sule Babayo , Mat Bakri , Mohd Sani Mohd Azizuddin , Ibrahim Saalah Yakubu
Published: August 2019

A periodic election is a fundamental pillar and backbone of any democratic regime, and for a proper election to take place there must be some activities, most especially by parties and contestants to vote for them most especially competing to secure the electorates. These activities require huge expenditure from the parties and their financiers through campaigns, media advertisements and other related activities. The problem is that parties and their candidates are allowed, in Nigeria constitutionally and by the Electoral Act 2010, to source their campaign finance privately, which has led to illegal financing. The objective of this paper is to examine the sources of parties’ campaign expenditure in the Fourth Republic, taking the 2015 General Election as the case study. The research used a qualitative method of data collection and analysis where both primary and secondary sources were used. The primary source was an in-depth personal interview with some selected informants/participants from the categories of stakeholders in the electoral process, parties, and agencies responsible for regulating their activities. The secondary source was the use of available documents such as books, journals and Internet sources on the subject matter of the study. The data obtained were analysed and interpreted using thematic analytical interpretations from the informants’ views and the existing data in the field. The research discovered that there are basically six major sources of campaign expenditure for parties and that some of the sources are illegal and the spending has violated the regulations. The research recommends thorough supervision and monitoring of the sources of parties’ campaign expenditure and the spending process.
Churning the Best Performer from the Last Performer! A Case Study on Innovations in B-Schools
Authors: George Filomina P.
Published: August 2019

Delivering quality business education in a complex and dynamic world is a major challenge for any Business School (B-School). It calls for constantly innovating new methods to entice, engage and enrich the learning experience of the students who go through a B-School programme. By meaningfully integrating such methods into the curriculum along with fulfilling the academic requirements leaves a longstanding impression on the learner. The Integrated Managerial Learning Program, branded as IMLP, is one such innovative method, which has stood the test of time easing out the transformation process during the two years tenure of the postgraduate programme in management. The following case describes the testimony of how IMLP has survived the dynamics of the changing world, transforming the last performer into the best performer, thus leaving a lasting impression on the students through a co-curricular activity, which is cherished by them at their workplaces and in almost every alumni meet.
Unequal Opportunity? Racial, Ethnic, and Gender Disparities in the Returns to Internal U.S. Migration
Authors: Leibbrand Christine
Published: August 2019

Internal U.S. migration plays an important role in increasing individuals’ access to economic and social opportunities. At the same time, race, ethnicity, and gender have frequently shaped the opportunities and obstacles individuals face. It is therefore likely that the returns to internal migration are also shaped by race, ethnicity, and gender, though we have relatively little knowledge of whether this is the case for contemporary internal U.S. migration. To explore this possibility, I use restricted, geocoded National Longitudinal Survey of Youth 1979 data from 1979 to 2012. I find that white men gain the most economically from migrating, relative to black and Latino men. For women, migration is associated with stable or narrower racial and ethnic disparities in economic outcomes, with Latina women experiencing the largest economic benefits associated with migration and with black and white women exhibiting comparable economic returns to migration. Together, these findings indicate that migration may maintain or even narrow racial/ethnic disparities in economic outcomes among women, but widen them among men.
Prevalence and Antibiotic Resistance of Stenotrophomonas maltophilia in Respiratory Tract Samples: A 10-Year Epidemiological Snapshot
Authors: Gajdács Márió , Urbán Edit
Published: August 2019

Background:

Since the 1980s, Stenotrophomonas maltophilia has emerged as an important pathogen associated with significant mortality in pneumonia and bacteremia of severely immunocompromised, hospitalized patients. The drug of choice in S maltophilia infections is sulfamethoxazole-trimethoprim (SMX/TMP); SMX/TMP resistance is a serious concern in clinical practice. The aim of this study was to assess the prevalence of S maltophilia in lower respiratory tract (LRTI) samples at a tertiary-care university hospital.

Methods:

This retrospective cohort study was carried out using microbiological data collected between January 2008 and December 2017. Routine antimicrobial susceptibility testing was performed for SMX/TMP and levofloxacin; in case of resistance, susceptibility testing for additional antibiotics (tigecycline, amikacin, and colistin) was also performed.

Results:

A total of 579 individual S maltophilia isolates were identified (2008-2012: n = 160, 2013-2017: n = 419; P = .0008). In all, 78.46% of patients were younger than 5 or older than 50 years of age and had recent trauma, surgery, or underlying conditions (malignancies, respiratory distress syndrome, congenital disorders, and cystic fibrosis). In 28.16% of samples, more than 1 pathogen was identified, and 5.35% of coisolated pathogens were multidrug resistant (MDR). In all, 12.1% of isolates were SMX/TMP-resistant (2008-2012: 6.12%, 2013-2017: 18.06%; P = .034), while 8.99% were resistant to levofloxacin (2008-2012: 7.86%, 2013-2017: 10.12%; P > .05). SMX/TMP resistance was detected more frequently in samples originating from inpatients (n = 2.50 ± 2.39 vs n = 11.50 ± 3.76; P = .0002).

Conclusions:

In all, 5.87% of isolates were extensively drug resistant (XDR), that is, in addition to SMX/TMP, they were resistant to levofloxacin, amikacin, colistin, and tigecycline. The results of our study correspond to the findings in the literature.
The application of FTIR microspectroscopy in a non-invasive and non-destructive way to the study and conservation of mineralised excavated textiles
Authors: Margariti Christina
Published: August 2019

The potential of Fourier Transform Infrared (FTIR) microspectroscopy, to inform the study and conservation of mineralised excavated textiles is discussed, highlighted by two case studies of 5th c. BCE finds. In both cases the textiles were funerary from pyre burials, used to wrap the remains of the incinerated bones of the deceased, and placed inside copper alloy urns, to be buried. FTIR spectra of the textile fibres were acquired by an FTIR microscope in reflectance mode. In regard to the two case studies, this was a non-invasive and non-destructive method, since it did not involve removal of material for sampling, as both finds were in a fragmentary condition, it did not apply any pressure, nor did it require pressing of the minute fragments used as samples. Past fibre analyses in case study A reported cultivated and wild silk, which had been used as evidence of the presence of silk in Classical Greece, while more recent studies, controversially pointed to either cellulosic or wool fibres. The unlimited application of FTIR microspectroscopy in reflectance mode due to its non-invasive/destructive nature, enhanced fibre identification but most importantly led to further analyses of specific fragments that revealed the find was suffering from active biodeterioration, subsequently treated. Case study B, where the textiles had been preserved folded, was a particularly unique find from its period, since one of the textiles present was bearing evidence of embroidery. Similarly, the extended application of FTIR microspectroscopy indicated good preservation of the organic matter within the fibres, informing thus the conservation decision-making process, which involved partial unfolding of the textiles, an action that revealed an additional decoration pattern, and minute fragments of the embroidery thread preserved.
Adding Authenticity to Inquiry in a First-Year, Research-Based, Biology Laboratory Course
Authors: Indorf Jane L. , Weremijewicz Joanna , Janos David P. , Gaines Michael S.
Published: August 2019

Course-based undergraduate research experiences (CUREs) are an effective way to integrate research into an undergraduate science curriculum and extend research experiences to a large, diverse group of early-career students. We developed a biology CURE at the University of Miami (UM) called the UM Authentic Research Laboratories (UMARL), in which groups of first-year students investigated novel questions and conducted projects of their own design related to the research themes of the faculty instructors. Herein, we describe the implementation and student outcomes of this long-running CURE. Using a national survey of student learning through research experiences in courses, we found that UMARL led to high student self-reported learning gains in research skills such as data analysis and science communication, as well as personal development skills such as self-confidence and self-efficacy. Our analysis of academic outcomes revealed that the odds of students who took UMARL engaging in individual research, graduating with a degree in science, technology, engineering, or mathematics (STEM) within 4 years, and graduating with honors were 1.5–1.7 times greater than the odds for a matched group of students from UM’s traditional biology labs. The authenticity of UMARL may have fostered students’ confidence that they can do real research, reinforcing their persistence in STEM.
Artificial Intelligence Treatment Decision Support For Complex Breast Cancer Among Oncologists With Varying Expertise
Authors: Xu Fengrui , Sepúlveda Martín-José , Jiang Zefei , Wang Haibo , Li Jianbin , Yin Yongmei , Liu Zhenzhen , Roebuck M. Christopher , Shortliffe Edward H. , Yan Min , Song Yuhua , Geng Cuizhi , Tang Jinhai , Rhee Kyu
Published: August 2019

PURPOSE

The aim of the current study was to assess treatment concordance and adherence to National Comprehensive Cancer Network breast cancer treatment guidelines between oncologists and an artificial intelligence advisory tool.

PATIENTS AND METHODS

Study cases of patients (N = 1,977) who were at high risk for recurrence or who had metastatic disease and cell types for which the advisory tool was trained were obtained from the Chinese Society for Clinical Oncology cancer database (2012 to 2017). A cross-sectional observational study was performed to examine treatment concordance and guideline adherence among an artificial intelligence advisory tool and 10 oncologists with varying expertise—three fellows, four attending physicians, and three chief physicians. In a blinded fashion, each oncologist provided treatment advice on an average of 198 cases and the advisory tool on all cases (N = 1,977). Results are reported as rates and logistic regression odds ratios.

RESULTS

Concordance for the recommended treatment was 0.56 for all physicians and higher for fellows compared with chief and attending physicians (0.68 v 0.54; 0.49; P = .001). Concordance differed by hormone receptor subtype–TNM stage, with the lowest for hormone receptor–positive human epidermal growth factor receptor 2/neu-positive cancers (0.48) and highest for triple-negative breast cancers (0.71) across most TNM stages. Adherence to National Comprehensive Cancer Network guidelines was higher for oncologists compared with the advisory tool (0.96 v 0.82; P < .003) and lower for fellows compared with attending physicians (0.93 v 0.98; 0.96; P = .04).

CONCLUSION

Study findings reflect a complex breast cancer case mix, the limits of medical knowledge regarding optimum treatment, clinician practice patterns, and use of a tool that reflects expertise from one cancer center. Additional research in different practice settings is needed to understand the tool’s scalability and its impact on treatment decisions and clinical and health services outcomes.
Validation of a Semiautomated Natural Language Processing–Based Procedure for Meta-Analysis of Cancer Susceptibility Gene Penetrance
Authors: Deng Zhengyi , Yin Kanhua , Bao Yujia , Armengol Victor Diego , Wang Cathy , Tiwari Ankur , Barzilay Regina , Parmigiani Giovanni , Braun Danielle , Hughes Kevin S.
Published: August 2019

PURPOSE

Quantifying the risk of cancer associated with pathogenic mutations in germline cancer susceptibility genes—that is, penetrance—enables the personalization of preventive management strategies. Conducting a meta-analysis is the best way to obtain robust risk estimates. We have previously developed a natural language processing (NLP) –based abstract classifier which classifies abstracts as relevant to penetrance, prevalence of mutations, both, or neither. In this work, we evaluate the performance of this NLP-based procedure.

MATERIALS AND METHODS

We compared the semiautomated NLP-based procedure, which involves automated abstract classification and text mining, followed by human review of identified studies, with the traditional procedure that requires human review of all studies. Ten high-quality gene–cancer penetrance meta-analyses spanning 16 gene–cancer associations were used as the gold standard by which to evaluate the performance of our procedure. For each meta-analysis, we evaluated the number of abstracts that required human review (workload) and the ability to identify the studies that were included by the authors in their quantitative analysis (coverage).

RESULTS

Compared with the traditional procedure, the semiautomated NLP-based procedure led to a lower workload across all 10 meta-analyses, with an overall 84% reduction (2,774 abstracts v 16,941 abstracts) in the amount of human review required. Overall coverage was 93%—we are able to identify 132 of 142 studies—before reviewing references of identified studies. Reasons for the 10 missed studies included blank and poorly written abstracts. After reviewing references, nine of the previously missed studies were identified and coverage improved to 99% (141 of 142 studies).

CONCLUSION

We demonstrated that an NLP-based procedure can significantly reduce the review workload without compromising the ability to identify relevant studies. NLP algorithms have promising potential for reducing human efforts in the literature review process.
Tissue/Site-Agnostic Study of Ribociclib for Tumors With Cyclin D–CDK4/6 Pathway Genomic Alterations: A Phase II, Open-Label, Single-Arm Basket Study
Authors: Peguero Julio , Sohal Davendra P. S. , O’Neil Bert H. , Safran Howard , Kelly Karen , Grilley-Olson Juneko E. , Subbiah Vivek , Nadauld Lincoln , Purkayastha Das , Stealey Erica , Ricart Alejandro D. , Kang Barinder P. , Eder Joseph Paul
Published: August 2019

PURPOSE

As part of the Novartis Signature Program, this study evaluated the efficacy of ribociclib (selective cyclin-dependent kinase 4/6 [CDK4/6] inhibitor) in patients with cyclin D–CDK4/6 pathway–aberrant tumors.

METHODS

This was a phase II, single-arm, signal-seeking study in patients with advanced malignancies that had progressed on or after standard treatment. Prior identification of tumor
CDK4/6
mutation or amplification,
CCND1
/3 amplification, or
CDKN2A
mutation or loss was required. Clinical benefit (defined as the proportion of patients with response or stable disease at ≥ 16 weeks) was the primary end point.

RESULTS

From 61 centers in the United States, 106 patients (median age, 62.5 years) were enrolled across multiple malignancies. The patient population was heavily pretreated (median number of prior therapies, three; range, 0 to 19). Median progression-free survival was 1.8 months (95% CI, 1.8 to 1.9). In patients with solid tumors, the clinical benefit rate was 18.1% (n = 19 of 105) and the overall response rate was 2.9% (n = 3 of 105); three partial responses occurred in patients with adenocarcinoma (unknown primary), soft tissue sarcoma, and urothelial carcinoma. No tumor cohort met the prespecified criteria for success. The most common adverse events suspected to be related to treatment were neutropenia (30.2%; decreased neutrophils, 15.1%), fatigue (31.1%), and nausea (29.2%). Fatigue and nausea were typically mild. Only one incident of febrile neutropenia was experienced (grade 3).

CONCLUSION

No new or unexpected safety signals were observed in this heavily pretreated patient population. Although responses were seen in tumors with
CCND1
–
CDK4/6
amplifications, the primary end point was not met, suggesting additional evaluation of ribociclib, possibly as combination therapy, is needed.
The Romantic Work of Genius: Author, Nature, Nation, and the “Genial Criticism” of Samuel Taylor Coleridge
Authors: Hess Scott
Published: August 2019

This essay explores how genius in the nineteenth century simultaneously constituted both individual and collective national identity, helping to produce new forms of liberal democratic nationalist culture. It offers a Latourian interpretation of genius in terms of the kind of social work and connections that the term enabled. Genius became associated in the late eighteenth and early nineteenth centuries with author, nature, and nation in ways that grounded new models of literature and identity in the supposedly transcendental truth of nature and in specific landscapes as “sites of memory.” This discourse of genius played a keystone role in Samuel Taylor Coleridge’s aesthetic and social criticism, or “genial criticism,” which exerted a deep influence on Anglophone culture. The essay concludes by assessing the overall cultural politics of genius in relation to various categories of identity, especially gender, and by suggesting how the “romantic work of genius” continues to operate and hold power in our (post)modern societies today.
C9ORF72-related cellular pathology in skeletal myocytes derived from ALS-patient induced pluripotent stem cells
Authors: Lynch Eileen , Semrad Theran , Belsito Vincent S. , FitzGibbons Claire , Reilly Megan , Hayakawa Koji , Suzuki Masatoshi
Published: August 2019

Amyotrophic lateral sclerosis (ALS) is a late-onset neuromuscular disease with no cure and limited treatment options. Patients experience a gradual paralysis leading to death from respiratory complications on average only 2-5 years after diagnosis. There is increasing evidence that skeletal muscle is affected early in the disease process, yet the pathological processes occurring in the skeletal muscle of ALS patients are still mostly unknown. Specifically, the most common genetic cause of ALS, a hexanucleotide repeat expansion in the C9ORF72 gene, has yet to be fully characterized in the context of skeletal muscle. In this study, we used the protocol previously developed in our lab to differentiate skeletal myocytes from induced pluripotent stem cells (iPSCs) of C9ORF72 ALS (C9-ALS) patients in order to create an in vitro disease model of C9-ALS skeletal muscle pathology. Of the three C9ORF72 mutation hallmarks, we did not see any evidence of haploinsufficiency, but we did detect RNA foci and dipeptide repeat (DPR) proteins. Additional abnormalities included changes in the expression of mitochondrial genes and a susceptibility to oxidative stress, indicating that mitochondrial dysfunction may be a critical feature of C9-ALS skeletal muscle pathology. Finally, the C9-ALS myocytes had increased expression and aggregation of TDP-43. Together, these data show that skeletal muscle cells experience pathological changes due to the C9ORF72 mutation. Our in vitro model could facilitate further study of cellular and molecular pathology in ALS skeletal muscle in order to discover new therapeutic targets against this devastating disease.

This article has an associated First Person interview with the first author of the paper.
Acute and sub-acute toxicity study of the root extracts of Fagaropsis hildebrandtii in mice and evaluation of their antimicrobial effects
Authors: Muia Beatrice Mwende , Mbaria James Mucunu , Kanja Laetitia Wakonyu , Gitahi Nduhiu , Okumu Paul Onyango , Okumu Mitchel Otieno
Published: August 2019

Background:Among the Kamba community of Kenya, roots ofFagaropsis hildebrandtii(FH) are boiled and used in managing cough, fertility problems, and microbial infections. The safety of this plant in oral administration and the validity of the ethnomedical claims is unverified. This study evaluated the toxicity of the aqueous and hexane root extracts of FH in mice and antimicrobial effects againstStaphylococcus aureus,Salmonella typhimuriumandCandida albicans.

Methods: Doses (300 and 2000mg/kg) of the extracts were administered orally to mice for 14 days. The weight, feed, and water consumption, organ weight of mice and gross macroscopy of the liver were used in evaluating acute toxicity. Mice were additionally treated with 250, 500, and 1000mg/kg body weight doses of the extracts for 28 days and haematological, biochemical, and histological parameters noted. The minimum inhibitory and minimum bactericidal/fungicidal concentrations (MIC; MBC/MFC) of the extracts against the aforementioned pathogens were determined by broth dilution.

Results:Acute oral toxicity of the extracts was >2000mg/kg, there were dose dependent changes in haematological and biochemical parameters, all female mice died when treated with doses of 1000mg/kg and doses ≥500mg/kg caused tubular degeneration and haemorrhage of the kidney, cloudy swelling of hepatocytes, and multifocal necrosis and pyknosis in the liver. The MBC/MIC ratio of each of the extracts againstStaph. aureusandS. typhimuriumwas 2, whileC. albicanswas not sensitive to any of the extracts.

Conclusions:Long term use of root extracts of FH was associated with dose-dependent changes in the kidney and liver of mice and changes in biochemical and haematological parameters. Root extracts of FH are bactericidal againstStaph. aureusandS. typhimuriumbut have no effect onC. albicans. Future work should aim at identifying the metabolites responsible for the observed toxic and bactericidal effects of the roots of FH.
Insights from quantitative and mathematical modelling on the proposed WHO 2030 goal for schistosomiasis
Authors:   NTD Modelling Consortium Schistosomiasis Group
Published: August 2019

Schistosomiasis remains one of the neglected tropical diseases (NTDs) impacting millions of people around the world. The World Health Organization (WHO) recently proposed a goal of elimination as a public health problem (EPHP) for schistosomiasis to be reached by 2030. Current WHO treatment guidelines for achieving EPHP focus on targeting school-aged children. The NTD Modelling Consortium has developed mathematical models to study schistosomiasis transmission dynamics and the impact of control measures. Our modelling insights on Schistosoma mansoni have shown that EPHP is likely to be attainable in low to moderate prevalence settings using the current guidelines. However, as prevalence rises within higher settings, EPHP is less likely to be achieved unless both school-aged children and adults are treated (with coverage levels increasing with the adult burden of infection). We highlight the challenges that are faced by treatment programmes, such as non-adherence to treatment and resurgence, which can hinder progress towards achieving and maintaining EPHP. Additionally, even though EPHP may be reached, prevalence can still be high due to persisting infections. Therefore, without elimination of transmission, treatment will likely have to continue to maintain EPHP. Further modelling work is being carried out, including extending our results to S. haematobium. By providing these modelling insights, we aim to inform discussions on the goals and treatment guidelines for schistosomiasis.
Testing the role of SOX15 in human primordial germ cell fate
Authors: Pierson Smela Merrick , Sybirna Anastasiya , Wong Frederick C.K. , Surani M. Azim
Published: August 2019

Background: Potentially novel regulators of early human germline development have been identified recently, including SOX15 and SOX17, both of which show specific expression in human primordial germ cells. SOX17 is now known to be a critical specifier of human germ cell identity. There have been suggestions, as yet without evidence, that SOX15 might also play a prominent role. The early human germline is inaccessible for direct study, but an in vitro model of human primordial germ cell-like cell (hPGCLC) specification from human embryonic stem cells (hESCs) has been developed. This enables mechanistic study of human germ cell specification using genetic tools to manipulate the levels of SOX15 and SOX17 proteins to explore their roles in hPGCLC specification.

Methods: SOX15 and SOX17 proteins were depleted during hPGCLC specification from hESCs using the auxin-inducible degron system, combined with a fluorescent reporter for tracking protein levels. Additionally, SOX15 protein was overexpressed using the ProteoTuner system. Protein-level expression changes were confirmed by immunofluorescence. The impact on hPGCLC specification efficiency was determined by flow cytometry at various time points. qPCR experiments were performed to determine some transcriptional effects of SOX15 perturbations.

Results: We observed specific SOX15 expression in hPGCLCs by using immunofluorescence and flow cytometry analysis. Depletion of SOX15 had no significant effect on hPGCLC specification efficiency on day 4 after induction, but there was a significant and progressive decrease in hPGCLCs on days 6 and 8. By contrast, depletion of SOX17 completely abrogated hPGCLC specification. Furthermore, SOX15 overexpression resulted in a significant increase in hPGCLC fraction on day 8. qPCR analysis revealed a possible role for the germ cell and pluripotency regulator PRDM14 in compensating for changes to SOX15 protein levels.

Conclusions: SOX17 is essential for hPGCLC specification, yet SOX15 is dispensable. However, SOX15 may have a role in maintaining germ cell identity.
Heat transfer
Authors: Чередниченко Владимир , Cherednichenko Vladimir , Синицын Валерий , Sinicyn Valeriy , Алиферов Александр , Aliferov Aleksandr , Шаров Юрий , Sharov Yuriy
Published: August 2019

The basic provisions of the theory of heat transfer, including thermal conductivity, convective and radiant heat transfer. The information about the methods of calculation of heat transfer in power engineering, electrical engineering, electromechanics and electrical engineering is given.
The first edition was published in 2004, the Material of the second edition in part updated and supplemented, the main attention is paid to the physical interpretation of the issues involved.
The manual can be useful for students of thermal power, Electromechanical, electrotechnological and engineering specialties, as well as a wide range of engineering and technical workers.
Incorporating a “Better” Behavioral Bias for Both Consumers and Firms in Rebate Programs
Authors: Chung Kevin
Published: August 2019

We study a rebate program in the credit card industry where the firm automatically processed the rebate earned by consumers with flexible and effortless redemption opportunities in future transactions. Contrary to what the normative economic theory would predict, we document that consumers frequently failed to redeem their rebate. Given this observation, we examine what may have been the primary driving force behind this pattern and the implications for the firm. We provide evidence that the phenomenon that we observe in our study is a result of cardholders being influenced by the way their outcomes were framed. We find that redemption incidences coincide with episodes where rebates are a larger portion of the amount spent. On the basis of the empirical regularities, we formulate a model of cardholder behavior where the cardholder experiences increasing psychological utility when rebate redemption yields a deeper discount. The model estimates indicate that, although delayed redemption left customers monetarily worse off in each transaction (cardholders passed up on average $0.76 of card-level benefits to experience greater psychological utility), once the psychological utility is taken into account, customers were shown to fare better overall. For the firm, in addition to the card benefits that were passed up, the psychological utility generated an additional average benefit of $1.21 per redemption. Finally, through counterfactuals we show that carefully designing a rebate program that takes into account consumers’ psychological redemption utility can further benefit both consumers and firms.

This paper was accepted by Juanjuan Zhang, marketing.