bluuebunny/crossref_metadata_2025 huggingface dataset:
Automated Vehicle Legislative Issues
Authors: Hubbard Sarah M. L.
Published: June 2018

This paper provides a synthesis of issues addressed by state legislation in relation to automated vehicles (AV); technologies are rapidly evolving and many states have developed legislation to govern AV testing and deployment and assure safety on public roads. The expected benefits of AV include increased safety, increased capacity, decreased congestion, increased productivity because of hands-free travel, and increased mobility for people who cannot drive. The projected economic impact of AV is significant, with an estimated market of $7 trillion by 2050. Potential challenges include increased costs, liability and licensing issues, privacy considerations, security and cybersecurity concerns, and potential job losses. Legislative responses to AV technology have varied significantly, depending on the state. Twenty-one states and the District of Columbia have passed legislation related to AV, and six states have executive orders. Even after federal AV legislation is passed, there will still be an important role for states in AV licensure, registration, insurance, traffic laws, enforcement, infrastructure, and emergency response. The objective of this research is to identify and synthesize current state legislation related to AV, which shows diverse responses and has led to a patchwork of operating conditions from state to state. The information presented in this paper provides important information as agencies and decision makers develop strategic plans for AV activities at every level, and serves an important function by documenting the evolution of issues related to AV which is an important part of transportation history.
Investigating the Impact of Fog on Freeway Speed Selection using the SHRP2 Naturalistic Driving Study Data
Authors: Khan Md Nasim , Ghasemzadeh Ali , Ahmed Mohamed M.
Published: June 2018

The negative effect of reduced visibility on driver performance has been recognized as one of the main causes of motor vehicle crashes in fog. Although many studies have concentrated on driver behavior during foggy weather in a simulated environment, there is a lack of studies that have addressed the impact of fog on driver behavior and performance in naturalistic settings. This paper utilized the data from the SHRP2 Naturalistic Driving Study (NDS) database to understand driver behavior in general and speed selection in particular during clear and foggy weather conditions. In this study, a comparative preliminary analysis and an ordered logit model were developed to evaluate driver speed behavior in fog and clear weather conditions. Results from the preliminary analysis showed 10% and 3% reduction in speed because of near fog and distant fog, respectively. In addition, results from the speed selection model showed that the odds of reducing speed were 1.31 and 1.28 times higher for drivers traveling in near fog and distant fog, respectively, compared with drivers who were driving in clear weather conditions. However, there is an over-representation of young drivers in the SHRP2 NDS database, which was reflected in the dataset used in this study. Therefore, a more representative sample of age groups might provide different results. The results from this study could provide a better insight into driver speed selection during foggy weather conditions, which can be utilized to improve various safety strategies including variable speed limits.
How Roundabout Entry Design Parameters Influence Safety
Authors: Novák Jan , Ambros Jiří , Frič Jindřich
Published: June 2018

Roundabouts are considered the safest intersection design; however, the safety effect may not be satisfactory at each specific roundabout. This is true especially in countries where roundabout design is a relatively new concept, such as in the Czech Republic. Specifically, most Czech roundabout crashes were found to occur on entries. This motivated the presented study to investigate how entry design parameters influence safety on Czech roundabouts and, if possible, use the findings to update current Czech roundabout design guidelines. To this end, the study comprised three analyses: crash-based safety performance functions, speed analysis, and finally safety performance functions which incorporated speed. All three analyses proved that entry design parameters have a statistically significant influence on safety, in terms of crash frequency, severity and speeds. Given the study objective, this fact should be considered in Czech roundabout design guidelines.
Virtual Immersive Reality for Stated Preference Travel Behavior Experiments: A Case Study of Autonomous Vehicles on Urban Roads
Authors: Farooq Bilal , Cherchi Elisabetta , Sobhani Anae
Published: June 2018

Stated preference experiments have been criticized for lack of realism. This issue is particularly visible when the scenario does not have a well understood prior reference, as in the case of research into demand for autonomous vehicles. The paper presents Virtual Immersive Reality Environment (VIRE), which is capable of developing highly realistic, immersive, and interactive choice scenarios. We demonstrate the use of VIRE in researching pedestrian preferences related to autonomous vehicles and associated infrastructure changes on urban streets in Montréal, Canada. The results are compared with predominantly used approaches: text-only and visual aid. We show that VIRE results in respondents having better understanding of the scenario and it yields more consistent results.
American Complete Streets and Australian SmartRoads: What Can We Learn from Each Other?
Authors: Delbosc Alexa , Reynolds James , Marshall Wesley , Wall Andrew
Published: June 2018

Road management in both Australasia and America has historically focused on facilitating vehicle movement and reducing congestion. More recently, however, there has been a shift to acknowledge the wider role that roads play in society. Road safety, equity impacts, considerations of “place” and the needs of different road users (including transit, pedestrians, and cyclists) are all gaining prominence. Two relatively new approaches to road design and management—Complete Streets in the United States and SmartRoads network operations planning in Australia—embody the spirit of this change. This paper summarizes the development of the Complete Streets movement in America and introduces the SmartRoads management framework, which was developed in the state of Victoria, Australia. In the SmartRoads process, roads within a network are classified in a multimodal Road User Hierarchy, network issues are identified using multimodal level of service measures, and possible operational or design solutions are compared using decision-making Network Fit Assessment software. We compare the scope, emphasis, and approach of the two frameworks; although they were developed at around the same time, the two approaches differ in significant ways. Yet the two approaches can learn from each other in order to significantly improve the management and design of roads in both Australia and the United States.
The Role of Liver Transplantation in Alcoholic Hepatitis
Authors: Ma Michelle , Falloon Katie , Chen Po-Hung , Saberi Behnam , Pustavoitau Aliaksei , Ozdogan Elif , Li Zhiping , Philosophe Benjamin , Cameron Andrew M. , Gurakar Ahmet
Published: June 2018

Acute alcoholic hepatitis is a syndrome of jaundice and hepatic decompensation that occurs with excessive alcohol consumption. The diagnosis can be made with a combination of clinical characteristics and laboratory studies, though biopsy may be required in unclear cases. Acute alcoholic hepatitis can range from mild to severe disease, as determined by a Maddrey discriminant function ≥32. Mild forms can be managed with supportive care and abstinence from alcohol. While mild form has an overall good prognosis, severe alcoholic hepatitis is associated with an extremely high short-term mortality of up to 50%. Additional complications of severe alcoholic hepatitis can include hepatic encephalopathy, gastrointestinal bleeding, renal failure, and infection; these patients frequently require intensive care unit admission. Corticosteroids may have short-term benefit in this group of patients if there are no contraindications; however, a subset of patients do not respond to steroids. New emerging therapies, which target hepatic regeneration, bile acid metabolism, and extracorporeal liver support, are being investigated. Liver transplantation for alcoholic liver disease was traditionally only considered in patients who have achieved 6 months of abstinence, in part due to social and ethical concerns regarding the use of a limited resource. However, the majority of patients with severe alcoholic hepatitis who fail medical therapy will not live long enough to meet this requirement. Recent studies have demonstrated that early liver transplantation in carefully selected patients with severe alcoholic hepatitis who fail medical therapy can provide a significant survival benefit and yields survival outcomes comparable to liver transplantation for other indications, with 6-month survival rates ranging from 77% to 100%. Alcohol relapse posttransplantation remains an important challenge, and heavy consumption can contribute to graft loss and mortality. Future investigation should address the substantial post-liver transplantation recidivism rate, from improving selection criteria to increasing posttransplantation substance abuse treatment resources.
Addressing Women and Minorities on Social Media by the 2016 U.S. Presidential Candidates
Authors: Bailey Mandi Bates , Nawara Steven P.
Published: June 2018

Donald Trump’s bombastic statements regarding women and minorities were a constant theme in the 2016 presidential election and attracted attention from both the mainstream media and his opponent, Hillary Clinton. Given the increasing use of social networking sites among political actors and the public, as well as the focus given to women and minorities in the 2016 election, we utilize a content analysis of presidential candidates’ social media activity in the months preceding the election in order to better understand how the candidates addressed women and minorities. We ultimately find that Democratic candidate Hillary Clinton out-posted Trump in both positive and negative content in the categories of women’s issues; lesbian, gay, bisexual, and transgender issues; race; and immigration. However, this is not the case with issues involving crime and police, which was a lens through which Trump was more likely to approach race-related issues. In many instances, the candidates also appeared to strategically target content-specific posts to the social media platforms where they would be most likely to be seen by women or the minority group most closely related to the post’s content.
Ground effect on a cropped slender reverse delta wing with anhedral and Gurney flaplike side-edge strips
Authors: Lee T , Huitema D , Leite P
Published: June 2018

The ground effect on the aerodynamic coefficients of a cropped slender reverse delta wing equipped with anhedral and Gurney flaplike side-edge strips was investigated experimentally at Re = 3.82 × 105. In a free stream, the 30% cropping was found to cause a minor reduction in lift CL and drag CD coefficients but a promoted stall compared to the noncropped wing. The anhedral caused further CL decrease and CD increase. Meanwhile, the application of side-edge strips produced a significantly increased CL and CD with a minor change to the CL/ CD ratio as compared to the baseline wing. In ground effect, the cropped wing was, however, found to generate more lift compared to the noncropped wing as the ground was approached. The joint anhedral and SES produced a great increment in both CL and CD but a virtually unchanged CL/ CD ratio compared to their outside ground effect counterparts. The larger the side-edge strips’ height the larger the increase in CL. In short, the cropping led to a weight reduction while the addition of anhedral and SES produced a large lift augmentation of the Lippisch-type wing-in-ground effect craft.
Improving finite element results in modeling heart valve mechanics
Authors: Earl Emily , Mohammadi Hadi
Published: June 2018

Finite element analysis is a well-established computational tool which can be used for the analysis of soft tissue mechanics. Due to the structural complexity of the leaflet tissue of the heart valve, the currently available finite element models do not adequately represent the leaflet tissue. A method of addressing this issue is to implement computationally expensive finite element models, characterized by precise constitutive models including high-order and high-density mesh techniques. In this study, we introduce a novel numerical technique that enhances the results obtained from coarse mesh finite element models to provide accuracy comparable to that of fine mesh finite element models while maintaining a relatively low computational cost. Introduced in this study is a method by which the computational expense required to solve linear and nonlinear constitutive models, commonly used in heart valve mechanics simulations, is reduced while continuing to account for large and infinitesimal deformations. This continuum model is developed based on the least square algorithm procedure coupled with the finite difference method adhering to the assumption that the components of the strain tensor are available at all nodes of the finite element mesh model. The suggested numerical technique is easy to implement, practically efficient, and requires less computational time compared to currently available commercial finite element packages such as ANSYS and/or ABAQUS.
Disinterring the Transition Debate in Maoist China
Authors: Majumdar Sayonee
Published: June 2018

This article tries to extricate the rationale behind China’s transition debate in the Maoist era (1949–1978). Using a re-casted theory of historical materialism (HM) to posit the shared ground of engagement of Chinese Marxists, I unpack the emergence of two competing development strategies for socialist transition, one which foregrounds forces of production (FOP) as the prime mover of this transition and the other class struggle to change relations of production (ROP) as the determining factor. I conclude by briefly discussing the shift from Mao Tse-tung to Deng Xiaoping’s era as a resolution of the development strategy in favour of the development of FOP as the key to China’s socialist transition.
From Fight or Flight, Freeze or Faint, to “Flow”: Identifying a Concept to Express a Positive Embodied Outcome of Trauma Recovery
Authors: Seng Julia , Group CAsCAid
Published: June 2018

BACKGROUND: The lifespan effects of adverse childhood experiences and their complex posttraumatic sequelae include early physical morbidity and mortality. Attention to physical sequelae and recovery is gaining clinical and research momentum. However, patient-centered communication in health care is hampered by lack of a common concept and word for a positive subjective, embodied outcome of trauma recovery. OBJECTIVE: To address this gap in theory, research, and practice vocabulary. DESIGN: We applied the six-step concept identification method described by Morse. RESULTS: The concept we identified is distinct from the trauma-reactive states of “fight or flight” and “freeze or faint.” We call it “flow.” CONCLUSIONS: Further deductive or inductive work to validate the concept would be useful as a step toward instrument development, followed by validation of its utility as a self-report proxy endpoint for patient centered health outcomes research. Qualitative research could be useful to elucidate the process of attaining “posttraumatic flow.”
Peripheral imbalanced TFH/TFR ratio correlates with intrathecal IgG synthesis in multiple sclerosis at clinical onset
Authors: Puthenparampil Marco , Zito Antonio , Pantano Giorgia , Federle Lisa , Stropparo Erica , Miante Silvia , De Silvestro Giustina , Plebani Mario , Gallo Paolo
Published: June 2018

Background:

Alteration of T-follicular helper (TFH) and regulatory (TFR) subpopulations may contribute to the development of auto-reactive B-cell.

Objective:

To investigate whether changes in TFH and TFR subsets are associated with abnormal IgG synthesis in blood and cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients.

Methods:

Paired blood and CSF samples were obtained from 31 untreated relapsing-remitting multiple sclerosis (RRMS) patients at diagnosis. Peripheral blood TFH (CD3+CD4+CXCR5+CD25–CD127+), TFR (CD3+CD4+CXCR5+CD25+CD127dim), conventional T-Helper (TH, CD3+CD4+CXCR5–CD25–CD127+), and regulatory T-cells (T-Reg, CD3+CD4+CXCR5–CD25+CD127dim) were analyzed in all RRMS patients and in 13 healthy controls (HCs). Qualitative and quantitative intrathecal IgG synthesis was evaluated in RRMS patients, who were then further subclassified according to the presence of IgG oligoclonal bands in blood and/or CSF.

Results:

Compared to HC, RRMS had lower TFR percentage ( p < 0.01) and higher TFH/TFR ratio ( p < 0.001). In RRMS, TFH/TFR ratio correlated with both qualitative ( r = 0.56, p < 0.005) and quantitative intrathecal IgG synthesis (IgG Index: r = 0.78; IgGLoc: r = 0.79; IgGIF: r = 0.76, all p < 0.001). Patients with the highest TFH/TFR ratios had higher percentages of circulating B-cells (36.1 ± 35.2%, p < 0.05).

Conclusion:

In RRMS, increased TFH/TFR ratio associates with abnormal IgG production in blood and CSF, suggesting that antibody-producing cells, derived from deregulated peripheral germinal center reaction, colonize the CNS.
Dirty Linen, Liminal Spaces, and Later Life: Meanings of Laundry in Care Home Design and Practice
Authors: Buse Christina , Twigg Julia , Nettleton Sarah , Martin Daryl
Published: June 2018

This article explores the design and practice of laundries and laundry work in care home settings. This is an often-overlooked aspect of the care environment, yet one that shapes lived experiences and meanings of care. It draws on ethnographic and qualitative data from two UK-based Economic and Social Research Council–funded studies: Buildings in the Making, a study of architects designing care homes for later life, and Dementia and Dress, a project exploring the role of clothing in dementia care. Drawing together these studies, the article explores the temporality and spatiality of laundry work, contrasting designers’ conceptions of laundry in terms of flows, movement, and efficiency with the lived bodily reality of laundry work, governed by the messiness of care and ‘body time’. The article examines how laundry is embedded within the meanings and imaginaries of the care home as a ‘home’ or ‘hotel’, and exposes the limitations of these imaginaries. We explore the significance of laundry work for supporting identity, as part of wider assemblages of care. The article concludes by drawing out implications for architectural design and sociological conceptions of care.
The meanings of belonging: Revisiting the theory of ‘belonging, being and becoming’ in the Australian Early Years Learning Framework
Authors: Peers Chris
Published: June 2018

The theory of belonging as it arises in the theme of the Australian Early Years Learning Framework suggests a complex arrangement of philosophical concepts, which deserve rigorous explication and interrogation. In this article, the author draws out some of the most pertinent implications of ‘belonging’ for the theory of early learning in Australia. In particular, the author addresses the risks associated with simplifying the term as a kind of knowledge that arises through social experience, without a meticulous explanation of what is meant by the ‘social’. The author also unpacks the possibilities surrounding ‘belonging’ if it is possible to think it outside vernacular definitions of property, with which the idea of belonging may easily be conflated. The aim is to provide a preliminary outline of philosophical approaches to ‘belonging’ to demonstrate that the Early Years Learning Framework may provide an important platform through which to think a new range of issues arising from the task of educating young children in Australia.
Predictors of extubation failure after open-chest cardiac surgery based on routinely collected data. The importance of a shared interprofessional clinical assessment
Authors: Sanson Gianfranco , Sartori Massimiliano , Dreas Lorella , Ciraolo Roberta , Fabiani Adam
Published: June 2018

Background:

Extubation failure (ExtF) is associated with prolonged hospital length of stay and mortality in adult cardiac surgery patients postoperatively. In this population, ExtF-related variables such as the arterial partial pressure of oxygen to fraction of inspired oxygen ratio (PaO2/FiO2), rapid shallow breathing index, cough strength, endotracheal secretions and neurological function have been sparsely researched.

Aim:

To identify variables that are predictive of ExtF and related outcomes.

Method:

Prospective observational longitudinal study. Consecutively presenting patients ( n=205) undergoing open-heart cardiac surgery and admitted to the Cardiosurgical Intensive Care Unit (CICU) were recruited. The clinical data were collected at CICU admission and immediately prior to extubation. ExtF was defined as the need to restart invasive or non-invasive mechanical ventilation while the patient was in the CICU.

Results:

The ExtF incidence was 13%. ExtF related significantly to hospital mortality, CICU length of stay and total hospital length of stay. The risk of ExtF decreased significantly, by 93% in patients with good neurological function and by 83% in those with a Rapid Shallow Breathing Index of ≥57 breaths/min per litre. Conversely, ExtF risk increased 27 times when the PaO2/FiO2was <150 and 11 times when it was ≥450. Also, a reassuring PaO2/FiO2value may hide critical pulmonary or extra-pulmonary conditions independent from alveolar function.

Conclusion:

The decision to extubate patients should be taken after thoroughly discussing and combining the data derived from nursing and medical clinical assessments. Extubation should be delayed until the patient achieves safe respiratory, oxygenation and haemodynamic conditions, and good neurocognitive function.
Managerial meta-knowledge and adaptation: Governance choice when firms don’t know their capabilities
Authors: Foss Nicolai J , Jensen Henrik
Published: June 2018

How well do managers know the capabilities of the firms they manage? Such knowledge, which we refer to as managerial meta-knowledge, has not been systematically addressed in the management and governance literature—which is problematic, as managerial meta-knowledge influences governance choice. In fact, transaction cost economics, the dominant theory of governance choice in management research, assumes that managers perfectly know the capabilities of their firms. However, micro-level research streams on resource cognition and transactive memory, as well as the knowledge-based view of strategy, suggest that this assumption is not in general warranted: Managers’ meta-knowledge is in general imperfect. We therefore examine the implications of imperfect managerial meta-knowledge for governance choice. The key mechanism we highlight is that imperfect managerial meta-knowledge leads to surprises and frictions in contractual relationships, negatively influences the ability to engage in coordinated adaptation, and is a driver of ex post transaction costs. For these reasons, managerial meta-knowledge holds implications for governance choices, which we summarize in four propositions.
The effects of ambient light on task switching depend on the chronotype
Authors: Yang J , Ru T , Chen Q , Mao T , Ji Y , Zhou G
Published: June 2018

The aim of the present study was to investigate the synchrony effect between chronotype and time of day on task switching and vigilance, and the effect of high illuminance on the performance of two chronotypes at their non-optimal time. Four 46 minute sessions were administrated on separate days, the illuminance (200 vs. 1200 lx at eye level) and time of day (1.5 hours vs. 10.5 hours after waking up) were manipulated within participants. We found that high illuminance (1200 lx) significantly decreased the latency switch cost only for evening type independent of time of day, and there was a trend that low illuminance (200 lx) was better for morning type to decrease latency switch cost compared with evening type. The high illuminance could decrease the subjective sleepiness significantly for both chronotypes at the later part of the experiment. No synchrony effect on task switching and vigilance was found in the present study. The results suggested that the effect of ambient light on task switching was modulated by chronotype. Current study enriched the research on the effect of ambient light on task switching. When setting the optimal light environment, we should considerate the individual difference such as chronotype.
Indoctrination, Islamic schools, and the broader scope of harm
Authors: Merry Michael S.
Published: June 2018

Many philosophers argue that religious schools are guilty of indoctrinatory harm. I think they are right to be worried about that. But in this article, I will postulate that there are other harms for many individuals that are more severe outside the religious school. Accordingly the full scope of harm should be taken into account when evaluating the harm that some religious schools may do. Once we do that, I suggest, justice may require that we choose the lesser harm. To simplify matters, I focus my attention on the stigmatic harm done to Muslims, and the role that Islamic schools might be expected to play in mitigating that harm. If the full weight of stigmatic harm is factored into the ethical analysis concerning Islamic schools, then I suggest that there are sufficiently weighty pro tanto reasons for Muslim parents to prefer an Islamic school over the alternatives, notwithstanding the potential indoctrinatory harm.
Application of modified Asimov’s laws to the agent of home service robot using state, operator, and result (Soar)
Authors: Van Dang Chien , Jun Mira , Shin Yong-Bin , Choi Jae-Won , Kim Jong-Wook
Published: June 2018

This study aims to interpret and apply Asimov’s Three Laws of Robotics to home service robots. An agent is developed herein with the ability to focus its attention on human beings’ health, particularly the elderly and the diseased, by delivering food. The agent is developed on a cognitive agent architecture, state, operator, and result (Soar), to enable effective reasoning and decision-making skills. This study deals with basic home care services, such as food delivery and emergency response; therefore, common food care and emergency rules are newly proposed based on the priority values that correspond to a family’s circumstances and/or emergency levels. Asimov’s Three Laws are modified to aid the home service robot to follow a predetermined order in selecting a food item or recommending an alternative food item suitable for its user’s prevailing health condition. Experimental results confirm that reasoning and decision-making of the proposed agent are logically and ethically valid for a home service robot and ensure compliance with both the original and modified Asimov’s Three Laws.
Morality as a Basic Psychological Need
Authors: Prentice Mike , Jayawickreme Eranda , Hawkins Ashley , Hartley Anna , Furr R. Michael , Fleeson William
Published: June 2018

We investigate the long-standing yet understudied assumption that feeling moral is a basic psychological need, perhaps like the needs to feel autonomous, competent, and related (ACR). We report an empirical “entrance exam” on whether morality should be considered a need. Specifically, we applied to morality a pioneering method from which Sheldon and colleagues provided evidence that ACR are basic psychological needs. In two studies and four samples, participants recalled events in which they felt un/satisfied, meaningful, pleasurable, at their best, and at their worst. They rated how much candidate psychological needs were satisfied during them. Morality was frequently as or more satisfied than ACR during peak events. Further, it was positively related to indices of positive functioning. These findings suggest feelings of being moral may help people identify times when life is going well. Further, they suggest that morality may be a fundamental psychological need and warrants further investigation.
Orbital and nasal meningoencephaloceles secondary to chronic hydrocephalus: A rare cause of bilateral proptosis
Authors: Jenner Zachary B , Husein Nuruddin , Riascos Roy , Esquenazi Yoshua
Published: June 2018

Introduction

Orbital meningoencephalocele formation is primarily a result of congenital defects in the pediatric population and trauma of the anterior cranial fossa in adults. We present a unique case of nontraumatic nasal and orbital meningoencephaloceles presenting as bilateral proptosis with exotropia secondary to chronic hydrocephalus.

Clinical presentation

A 20-year-old male with a history of tuberous sclerosis, X-linked intellectual disability, and epilepsy presented to the emergency department with two days of nausea, emesis, seizures, and two months of progressive proptosis. Initial radiographs of the skull showed a “copper beaten” appearance, indicating chronically elevated intracranial pressure. Computed tomography imaging of the head demonstrated bilateral defects in the cribriform plate and anterior cranial fossa. Magnetic resonance imaging of the brain revealed triventricular hydrocephalus with meningoencephalocele extension into the nasal cavity and frontal horn herniation into the extraconal space of the orbits. The hydrocephalus was managed with ventriculoperitoneal shunt placement with rapid and complete resolution of the proptosis.

Conclusion

No reports have described bilateral proptosis as the presenting finding of orbital and nasal meningoencephaloceles in the absence of trauma or congenital defect. This case study demonstrates the management of meningoencephalocele formation secondary to chronic hydrocephalus.
The effect of age on stem cell function and utility for therapy
Authors: Narbonne Patrick
Published: June 2018

During development, stem cells generate all of the differentiated cells that populate our tissues and organs. Stem cells are also responsible for tissue turnover and repair in adults, and as such, they hold tremendous promise for regenerative therapy. Aging, however, impairs the function of stem cells and is thus a significant roadblock to using stem cells for therapy. Paradoxically, the patients who would benefit the most from regenerative therapies are usually advanced in age. The use of stem cells from young donors or the rejuvenation of aged patient-derived stem cells may represent part of a solution. Nonetheless, the transplantation success of young or rejuvenated stem cells in aged patients is still problematic, since stem cell function is greatly influenced by extrinsic factors that become unsupportive with age. This article briefly reviews how aging impairs stem cell function, and how this has an impact on the use of stem cells for therapy.
Metformin induces FOXO3-dependent fetal hemoglobin production in human primary erythroid cells
Authors: Zhang Yankai , Paikari Alireza , Sumazin Pavel , Ginter Summarell Carly C. , Crosby Jacy R. , Boerwinkle Eric , Weiss Mitchell J. , Sheehan Vivien A.
Published: June 2018

Key Points

Functional studies in human primary erythroid progenitor cells support a role for FOXO3 in γ-globin regulation. Metformin treatment of human primary erythroid progenitor cells increases fetal hemoglobin in a partially FOXO3-dependent manner.
A generalized average-derivative optimal finite-difference scheme for 2D frequency-domain acoustic-wave modeling on continuous nonuniform grids
Authors: Li Quanli , Jia Xiaofeng
Published: June 2018

The frequency-domain finite-difference (FDFD) method is an effective tool for implementing frequency-domain seismic modeling, inversion, and migration. However, the computational cost for the FDFD method dealing with large models is prohibitive, limiting its application. As a common strategy to improve the computational efficiency, a nonuniform grid is usually adopted in the time-domain finite-difference method instead of the FDFD method. We have developed a generalized average-derivative optimal scheme (GADOS) that can perform frequency-domain acoustic-wave modeling on continuous nonuniform grids in the vertical and horizontal directions. Before we begin the calculations, we optimize numerous stencils in which the grid spacing ratios are different to obtain a large dictionary composed of many groups of optimal coefficients. We consider the continuous nonuniform grids as a gathering of nonuniform nine-point stencils (i.e., the stencil of the GADOS) and select the proper weighted coefficients for every stencil to ensure that the numerical dispersion is minimal in the global area. All the phase-velocity errors of the GADOS for different grid spacing ratios are less than [Formula: see text] even if the number of grid points per wavelength is as small as four after the weighted coefficients are optimized by minimizing the numerical dispersion. Compared with the average-derivative optimal scheme (ADOS), simulating seismic waves with the GADOS on nonuniform grids reduce the computational cost with the premise of ensuring sufficient accuracy. Several numerical examples are presented to illustrate the feasibility and efficiency of the GADOS on continuous nonuniform grids.
Induced polarization response of porous media with metallic particles — Part 7: Detection and quantification of buried slag heaps
Authors: Qi Youzheng , Soueid Ahmed Abdellahi , Revil André , Ghorbani Ahmad , Abdulsamad Feras , Florsch Nicolas , Bonnenfant Jeremy
Published: June 2018

With the progress of metallurgical activities, more and more dumped slag heaps emerge as valuable deposits to feed the growing need for metal resources. Detecting, quantifying, and reextracting metals from these slags may complement the prospection of new ore deposits. However, the spatial delineation of the slag heap cannot easily be obtained from the resistivity distribution alone (determined either with galvanometric or with induction-based methods). Although the magnetic method can detect slag heaps, it fails to make an estimation of the quantity of metal present in the slag. Alternatively, the induced polarization (IP) method can be used to fulfill this goal. The complex conductivity responses of slag samples from a slag heap in France are obtained in the laboratory. These data are used to assess the grade of the slag, which is close to 8%. Then, a least-squares 3D IP inversion is used to get the subsurface chargeability distribution delimiting the slag heap in the ground. From the linear relationship determined between the chargeability and the volumetric metal content or the volumetric slag content, the metallic volume of the slag heaps can be directly determined. This approach is used at the site of Saint-Vincent sur L'Isle, Dordogne (France), where it allows characterizing the shape of a slag heap and quantifying the total cumulative metal content of the investigated area.
Results of the downhole microseismic monitoring at a pilot hydraulic fracturing site in Poland — Part 1: Event location and stimulation performance
Authors: Gajek Wojciech , Trojanowski Jacek , Malinowski Michał , Jarosiński Marek , Riedel Marko
Published: June 2018

A precise velocity model is necessary to obtain reliable locations of microseismic events, which provide information about the effectiveness of the hydraulic stimulation. Seismic anisotropy plays an important role in microseismic event location by imposing the dependency between wave velocities and its propagation direction. Building an anisotropic velocity model that accounts for that effect allows for more accurate location of microseismic events. We have used downhole microseismic records from a pilot hydraulic fracturing experiment in Lower-Paleozoic shale gas play in the Baltic Basin, Northern Poland, to obtain accurate microseismic events locations. We have developed a workflow for a vertical transverse isotropy velocity model construction when facing a challenging absence of horizontally polarized S-waves in perforation shot data, which carry information about Thomsen’s [Formula: see text] parameter and provide valuable constraints for locating microseismic events. We extract effective [Formula: see text], [Formula: see text] and [Formula: see text], [Formula: see text] for each layer from the P- and SV-wave arrivals of perforation shots, whereas the unresolved [Formula: see text] is retrieved afterward from the SH-SV-wave delay time of selected microseismic events. An inverted velocity model provides more reliable location of microseismic events, which then becomes an essential input for evaluating the hydraulic stimulation job effectiveness in the geomechanical context. We evaluate the influence of the preexisting fracture sets and obliquity between the borehole trajectory and principal horizontal stress direction on the hydraulic treatment performance. The fracturing fluid migrates to previously fractured zones, while the growth of the microseismic volume in consecutive stages is caused by increased penetration of the above-lying lithologic formations.
Acute Myeloid Leukemia: The Good, the Bad, and the Ugly
Authors: Kuykendall Andrew , Duployez Nicolas , Boissel Nicolas , Lancet Jeffrey E. , Welch John S.
Published: June 2018

Acute myeloid leukemia (AML) was initially subdivided according to morphology (the French-American-British system), which proved helpful in pathologic categorization. Subsequently, clinical and genomic factors were found to correlate with response to chemotherapy and with overall survival. These included a history of antecedent hematologic disease, a history of chemotherapy or radiation therapy, the presence of various recurrent cytogenetic abnormalities, and, more recently, the presence of specific point mutations. This article reviews the biology and responses of one AML subgroup with consistent response and good outcomes following chemotherapy (core-binding factor leukemia), and two subgroups with persistently bad, and even ugly, outcomes (secondary AML and TP53-mutated AML).
Major Changes in Head and Neck Staging for 2018
Authors: Lydiatt William , O’Sullivan Brian , Patel Snehal
Published: June 2018

Oncologists should be aware of three major modifications and additions to staging head and neck cancer that became effective in 2018. Oral cavity cancers have the addition of depth of invasion; oropharyngeal cancers (OPCs) are now distinguished by the immunohistochemical stain, p16, into those that are associated with high-risk human papillomavirus and those that are not; and all sites except nasopharyngeal carcinoma and high-risk human papillomavirus OPC will now include the important parameter of extranodal extension. The rationale and emerging data supporting these changes are discussed in this article and the accompanying oral presentation at the 2018 ASCO Annual Meeting.
Ultimate Precision: Targeting Cancer but Not Normal Self-replication
Authors: Velcheti Vamsidhar , Schrump David , Saunthararajah Yogen
Published: June 2018

Self-replication is the engine that drives all biologic evolution, including neoplastic evolution. A key oncotherapy challenge is to target this, the heart of malignancy, while sparing the normal self-replication mandatory for health and life. Self-replication can be demystified: it is activation of replication, the most ancient of cell programs, uncoupled from activation of lineage-differentiation, metazoan programs more recent in origin. The uncoupling can be physiologic, as in normal tissue stem cells, or pathologic, as in cancer. Neoplastic evolution selects to disengage replication from forward-differentiation where intrinsic replication rates are the highest, in committed progenitors that have division times measured in hours versus weeks for tissue stem cells, via partial loss of function in master transcription factors that activate terminal-differentiation programs (e.g., GATA4) or in the coactivators they use for this purpose (e.g., ARID1A). These loss-of-function mutations bias master transcription factor circuits, which normally regulate corepressor versus coactivator recruitment, toward corepressors (e.g., DNMT1) that repress rather than activate terminal-differentiation genes. Pharmacologic inhibition of the corepressors rebalances to coactivator function, activating lineage-differentiation genes that dominantly antagonize MYC (the master transcription factor coordinator of replication) to terminate malignant self-replication. Physiologic self-replication continues, because the master transcription factors in tissue stem cells activate stem cell, not terminal-differentiation, programs. Druggable corepressor proteins are thus the barriers between self-replicating cancer cells and the terminal-differentiation fates intended by their master transcription factor content. This final common pathway to oncogenic self-replication, being separate and distinct from the normal, offers the favorable therapeutic indices needed for clinical progress.
Complexity of Delivering Precision Medicine: Opportunities and Challenges
Authors: Davis Andrew A. , McKee Amy E. , Kibbe Warren A. , Villaflor Victoria M.
Published: June 2018

Precision medicine has emerged as a tool to match patients with the appropriate treatment based on the precise molecular features of an individual patient’s tumor. Although examples of targeted therapies exist resulting in dramatic improvements in patient outcomes, comprehensive genomic profiling of tumors has also demonstrated the incredible complexity of molecular alterations in tissue and blood. These sequencing methods provide opportunities to study the landscape of tumors at baseline and serially in response to treatment. These tools also serve as important biomarkers to detect resistance to treatment and determine higher likelihood of responding to particular treatments, such as immune checkpoint blockade. Federally funded and publicly available data repositories have emerged as mechanisms for data sharing. In addition, novel clinical trials are emerging to develop new ways of incorporating molecular matched therapy into clinical trials. Various challenges to delivery of precision oncology include understanding the complexity of advanced tumors based on evolving “omics” and treatment resistance. For physicians, determining when and how to incorporate genetic and molecular tools into clinic in a cost-effective manner is critical. Finally, we discuss the importance of well-designed prospective clinical trials, biomarkers such as liquid biopsies, the use of multidisciplinary tumor boards, and data sharing as evidence-based medicine tools to optimally study and deliver precision oncology to our patients.
New Treatment Algorithms in Hodgkin Lymphoma: Too Much or Too Little?
Authors: Spinner Michael A. , Advani Ranjana H. , Connors Joseph M. , Azzi Jacques , Diefenbach Catherine
Published: June 2018

Hodgkin lymphoma treatment continues to evolve as new means of assessing response to treatment, new appreciation of important risk factors, and more effective therapeutic agents become available. Treatment algorithms integrating functional imaging now provide the opportunity to modify therapy during its delivery, allowing adjustment of duration and intensity of chemotherapy and rationale identification of patients who may benefit from the addition of therapeutic irradiation. Novel agents, including the antibody drug conjugate brentuximab vedotin and checkpoint inhibitors such as nivolumab and pembrolizumab can improve the effectiveness of treatment while keeping toxicity within acceptable limits. Carefully designed clinical trials permit the identification of superior approaches in which efficacy is enhanced and toxicity minimized. Clinicians treating patients with Hodgkin lymphoma now have access to novel treatment approaches, which will require detailed assessment of each patient and careful discussion of the goals and risks of treatment at the time of planning primary treatment, again during delivery of that treatment as data indicating ongoing effectiveness become available, at the conclusion of initial intervention, and, when the need arises, at the time of recurrence of disease.
The Landscape of CAR T Cells Beyond Acute Lymphoblastic Leukemia for Pediatric Solid Tumors
Authors: DeRenzo Christopher , Krenciute Giedre , Gottschalk Stephen
Published: June 2018

Adoptive cell therapy with genetically modified T cells holds the promise to improve outcomes for children with recurrent/refractory solid tumors and has the potential to reduce treatment complications for all patients. Although T cells that express chimeric antigen receptors (CARs) specific for CD19 have had remarkable success for B-cell–derived malignancies, which has led to their approval by the U.S. Food and Drug Administration, CAR T cells have been less effective for solid tumors and brain tumors. Lack of efficacy is most likely multifactorial, but heterogeneous antigen expression; limited migration of T cells to tumor sites; and the immunosuppressive, hostile tumor microenvironment have emerged as major roadblocks that must be addressed. In this review, we summarize the clinical experience with CAR T-cell therapy for pediatric solid tumors, including brain tumors. In addition, we review strategies that have been and are being developed to enhance their antitumor activity.
Filling the Gap: Creating an Outpatient Palliative Care Program in Your Institution
Authors: Finlay Esme , Rabow Michael W. , Buss Mary K.
Published: June 2018

Well-designed, randomized trials demonstrate that outpatient palliative care improves symptom burden and quality of life (QOL) while it reduces unnecessary health care use in patients with cancer. Despite the strong evidence of benefit and ASCO recommendations, implementation of outpatient palliative care, especially in community oncology settings, faces considerable hurdles. This article, which is based on published literature and expert opinion, presents practical strategies to help oncologists make a strong clinical and fiscal case for outpatient palliative care. This article outlines key considerations for how to build an outpatient palliative care program in an institution by (1) defining the scope and benefits; (2) identifying strategies to overcome common barriers to integration of outpatient palliative care into cancer care; (3) outlining a business case; (4) describing successful models of outpatient palliative care; and (5) examining important factors in design and operation of a palliative care clinic. The advantages and disadvantages of different delivery models (e.g., embedded vs. independent) and different methods of referral (triggered vs. physician discretion) are reviewed. Strategies to make the case for outpatient palliative care that align with institutional values and/or are supported by local institutional data on cost savings are included.
Assessing the Value of Next-Generation Sequencing Tests in a Dynamic Environment
Authors: Burris Howard A. , Saltz Leonard B. , Yu Peter P.
Published: June 2018

Next-generation sequencing (NGS)–based technology has lowered the cost of cancer testing for genomic alterations and is now commercially available from a growing number of diagnostic laboratories. However, laboratories vary in the methodologies underlying their tests, the types and numbers of genomic alterations covered by the test, and the clinical annotation of the sequencing findings. Determining the value of NGS tests is dependent on whether it is used to support clinical trials or as a part of routine clinical care at a time when both the investigational drug pipeline and the list of U.S. Food and Drug Administration–approved or Compendium-listed therapeutics is in a high state of flux. Reimbursement policy for NGS testing by the Centers for Medicare & Medicaid is evolving as the value of NGS testing becomes more clearly defined for specific clinical situations. Patient care and clinical decisions-making are dependent on the oncologist’s knowledge of when NGS testing has value. Here, we review principles and practice for NGS testing in this dynamic confluence of technology, cancer biology, and health care policy.