cssi/SciSciGPT-SciSciNet huggingface dataset:
Modeling the Kinematic Wave Parameters with Regression Methods

The momentum equation in the kinematic wave model is a power law equation and involves two kinematic wave parameters. It is a common practice to use Manning’s equation to calculate the kinematic wave parameters. One can obtain a kinematic wave equation by inserting the momentum equation into the continuity equation. The kinematic wave equation becomes a partial differential equation with kinematic wave parameters that depend on the flow depth. However, working with the kinematic wave equation comprised of kinematic wave parameters that are independent of the flow depth, is a lot more convenient. Here, regression methods were used to calculate the kinematic wave parameters that are independent of the flow depth for a trapezoidal channel cross-section, which is a common cross-section shape. The developed expressions for the kinematic wave parameters provided very good approximation for the momentum equation of the kinematic wave model. The relationships among the geometry parameters of natural channel cross...
Analysis of the quantitative measurement for a lateral shear interferometer in a convergent beam mode using Fourier transform method

Lateral shear interferometry operating in the convergent beam mode has been used for testing optical components. This method is simple and phase information of the wavefront has conventionally been extracted using phase stepping techniques. We propose to use defocus, which introduces uniform tilt as a means of extracting phase information via two procedures, namely spatial phase stepping and spatial frequency carrier method. Experimental results are presented that show the wavefront phase extracted with defocus before and after the focal point of the lens.
The impact of corporate income tax rate on foreign direct investment in Australia and implications for technology transfer

FDI is an important channel through which technology can be transferred across countries. The increased mobility of capital and the globalisation have influenced tax competition among countries to attract foreign investment. This paper investigates the effects of company tax rate on FDI stocks into Australia over the period 1960-2003 using time series econometric techniques. The results show that Australia has a potential to attract FDI by lowering its company tax rate. The findings suggest that lowering the taxes by host country to attract FDI would also in effect help the country to accumulate its technological stock enhancing its global competitiveness.
Carbon accounting rules and guidelines for the United States forest sector.

The United States Climate Change initiative includes improvements to the U.S. Department of Energy's Voluntary Greenhouse Gas Reporting Program. The program includes specific accounting rules and guidelines for reporting and registering forestry activities that reduce atmospheric CO2 by increasing carbon sequestration or reducing emissions. In the forestry sector, there is potential for the economic value of emissions credits to provide increased income for landowners, to support rural development, to facilitate the practice of susbinable forest management, and to support restoration of ecosystems. Forestry activities with potential for achieving substantial reductions include, but are not limited to: afforestation, mine land reclamation, forest restoration, agroforestry, forest mamgement, short-rotation biomass energy plantations, forest protection, wood production, and urban forestry. To be eligible for registration, the reported reductions must use methods and meet standards contained in the guidelines. Forestry presents some unique challenges and opportunities because of the diversity of activities, the variety of practices that can affect greenhouse gases, year-to-year variability in emissions and sequestration, the effects of activities on different forest carbon pools, and accounting for the effects of natural disturbance.
The Neuroendocrine Loop Model Revisited: Is It Valid or Even Relevant?

Biological rhythms and the biological clocks that control them are fundamental properties of most living organisms, ranging from several forms of bacteria to multicellular plants and animals. These properties share many formal and biochemical properties, and affect all aspects of physiological function, ranging from control of transcription to metabolism to cell cycle to behavior. Because these rhythms are expressed similarly in single-celled and multi-cellular organisms, and because clock function pervades all levels of biological organization, many authors have suggested that biological clocks are properties of all cells.1
Variable and Nonspherical Stellar Winds in Luminous Hot Stars: IAU Colloquium 169*

The winds of hot stars are generally understood to be driven by the absorption of momentum from the intense stellar radiation field by line transitions in the ultraviolet and farultraviolet regions of the spectrum. Observational diagnostics of these dense winds can be reproduced quite well for most early-type stars within the context of a “standard model,” in which the outflow is spherically symmetric, smooth, and steady. This model serves as a useful starting point for estimating global properties such as mass-loss rates and for investigating the various ways that winds interact with their local interstellar environments. However, there is abundant evidence that essentially all hot-star winds contain time-dependent structure on a variety of spatial scales. Observations of anisotropy, clumpiness, and variability contradict the assumptions of the standard model and imply that our understanding of mass loss via stellar winds is still incomplete. IAU Colloquium 169 was convened to review the observational evidence for variability and asphericity in hotstar winds; to discuss the physical processes that might cause such behavior; and to look for evolutionary consequences. The meeting was hosted by the Landessternwarte HeidelbergKonigstuhl, a venue that was fitting not only because 1998 marked the centennial of its founding, but also because of its enviable history as a center for hot-star research. The meeting attracted nearly 150 researchers from 26 countries. Over the course of four and one-half days, 62 oral review and contributed papers and approximately 70 poster papers were presented. The topics of these papers included both garden-variety OBA stars and their more exotic cousins: Be stars, Wolf-Rayet stars, and the rare B[e] stars and luminous blue variables (LBVs). The role played by rotation in shaping the emergence of the stellar wind was a recurrent theme in these presentations and also provides a framework for this brief report on the meeting. The proceedings contain comprehensive discussions of these and other highlights, which included reports of impressive progress in modeling disk winds; analysis and simulations of the nebulae ejected by hot stars in episodic mass-loss events; and distance determination from quantitative spectral analysis of the photospheres and winds of hot stars. Rotation is the most obvious, universal process that can induce large-scale asphericity in the stellar winds of single stars, and it is therefore not surprising that it was a focus for this
SURVIVAL AND HABITAT USE OF MALLARD (ANAS PLATYRHYNCHOS) BROODS IN THE SAN JOAQUIN VALLEY, CALIFORNIA

Abstract The Central Valley of California is an important breeding area for Mallards (Anas platyrhynchos), but estimating recruitment rates for this population has been hampered by lack of data on duckling survival. To gain a better understanding of factors affecting brood and duckling survival, we radiomarked 56 brood hens and 112 ducklings (two per brood) on two actively managed wetland complexes in the San Joaquin Valley during 1996-1997. Total brood mortality was extensive, affecting 27 of 53 broods (51%). Survival of individual ducklings from hatching until 30 days of age was 24.8% (95% confidence interval: 0.178–0.335), with most mortality resulting from predation during the first 12 days of life. Survival differed between years and study areas but was unaffected by hatching date. Broods preferred reverse-cycle seasonal wetlands to more permanent wetlands throughout their first 30 days of life, and ducklings also had higher 2- to 30-day survival probabilities in reverse-cycle wetlands (x ± SE = 0.7...
Editorial: Clinical policy for children younger than three years presenting to the emergency department with fever.

In this issue of Annals, the American College of Emergency Physicians (ACEP) Clinical Policies Committee presents ACEP’s “Clinical Policy for Children Younger Than Three Years Presenting to the Emergency Department With Fever.”1 This evidence-based guideline is one of many developed by this committee and published in Annals. I am pleased that so many physicians and medical organizations have recognized the value of evidence-based medicine, have overcome initial apprehensions about “cookbook medicine” and potential malpractice risks, and have adopted the use of complaintspecific guidelines as a starting point to determine the appropriate diagnostic tests and treatments in carefully selected groups of patients. I await the day when these guidelines will be incorporated into an electronic medical record and can be used contemporaneously with patient care by the majority of practicing physicians.2,3 In general, this clinical policy restates much of what was noted in an article I authored in Annals in 2000, which was an update of a guideline developed by experts in pediatric emergency medicine and pediatric infectious diseases published simultaneously in Pediatrics and Annals of Emergency Medicine in 1993.4,5 The original guideline was primarily created for the following reasons: (1) to reduce the number of hospital admissions in the 1to 3-month age group using the P E D I A T R I C S / E D I T O R I A L
Emerging Cardiac Devices and Technologies

The primary goals of this last chapter are to: (1) discuss, in more detail, some of the technologies mentioned earlier in this book; (2) introduce readers to several additional technological advances associated with cardiovascular health care that have been recently introduced, are currently in clinical testing, or will soon be released; and (3) discuss future opportunities in the cardiac device arena. It should be noted that other areas of importance in cardiac treatment such as biological approaches to disease management (e.g., stem cell therapy), genomics (i.e., diagnostics and gene therapy), proteomics, and/or tissue engineering will also have a major impact on the future of cardiac clinical care, yet detailed discussions of these approaches are beyond the scope of this text. More specifically, in this last chapter, we will review several innovations in the following areas: (1) resuscitation systems and devices; (2) implantable therapies; (3) delivery systems; (4) invasive therapies; (5) procedural improvements; (6) less invasive surgical approaches; (7) post-procedural follow-ups; and/or (8) training tools.
‘Just Trying to Be Human in this Place’: Storytelling and Film in the First-Year Law School Classroom

In 2007, the latest in a long line of studies and research projects that critically examined American legal education were published. The Carnegie Foundation Report, “Educating Lawyers: Preparation for the Profession of Law”, and the empirical research findings of linguistic anthropologist Elizabeth Mertz, “The Language of Law School: Learning to 'Think Like A Lawyer'”, identified many shortcomings and negative consequences that result from the traditional pedagogy of the American law school classroom. In this Article, Professors Kate Nace Day and Russell G. Murphy explore some of the findings of these studies in the context of their experimentation with the use of storytelling, feature films, and documentaries in first year law classes. The Article suggests that these materials can effectively supplement doctrinal teaching by “humanizing” the first year experience through refocusing on the real world experiences of lawyers and clients, examining the social consequences of legal controversies, and factoring “justice” into the case dialogue method. Further, in light of Mertz’s findings on the disturbing silences in the classroom, the Article argues that storytelling and film can transform the vision of law received by outsider students.
Pharmacotherapy of Insomnia in Children

Insomnia is defined as the inability to fall asleep and/or the inability to maintain sleep to the point that it has a negative impact on time awake. Insomnia in adults may lead to daytime fatigue and sleepiness but in children, the lack of quality sleep may lead to daytime behavioral problems such as hyperactivity and academic difficulty. The pharmacological treatment of insomnia in children is a challenging problem for clinicians since there is paucity of Food and Drug Administration (FDA) approved. Parents often seek medical attention for their children when their own or other members of the family’s sleep schedule has been disrupted. The clinician has to take into account the entire family when evaluating a child and making therapeutic recommendations. When evaluating a child with insomnia, it is not only important to take a thorough history of the child’s sleep schedule but it also involves getting a detailed evaluation of the other family member’s sleep history. The pharmacological management of insomnia is dependent on the child’s age. The primary healthcare physician may have limited training in pediatric sleep disorders. Although the mainstay treatment for insomnia in children is behavioral therapy, in this chapter, we will provide a review of the medications that may be used as an adjunct treatment for pediatric insomnia.
Feedback Control of Mammalian Cell Differentiation

Slow, ongoing terminal cell differentiation is essential for replacing aging or damaged cells and for maintaining tissue size in all adult mammals. For example, cardiomyocytes and adipocytes (fat cells) renew in humans at a rate of 1% and 10% per year, respectively. Using computational modeling, single-cell imaging, and quantitative mass spectrometry, we identified a highly-feedback connected system architecture that can control such low rates of differentiation in fat cells and have continued to explore the kinetics and molecular mechanisms of how this system filters physiological inputs with the goal to open up new venues for therapeutically regulating adipose tissue renewal and size. The results may have broad relevance for all terminal cell differentiation processes including those in cardiac, neuronal, hematopoietic, and other tissues.
Impoverished acoustic input triggers probability-based tone processing in mono-dialectal Mandarin listeners

Abstract Previous research on Mandarin spoken word recognition suggests that when processing lexical tone native listeners tune to various acoustic properties of the incoming signal such as f 0 height, contour and change. These studies overlook the uneven distribution of tone across the Mandarin lexicon; given a particular string of segments, native listeners may be more likely to anticipate a certain tone due to prior experience with the language. The present study used the gating paradigm to investigate how much of the acoustic signal is needed for listeners to trigger such probability-based tone processing. Duration-blocked gates were generated from twelve low frequency and twelve high frequency mono-syllabic morphemes, with each syllable carrying either the most or least probable tone based on spoken corpora. Results from 22 mono-dialectal Mandarin speakers indicate that listeners immediately begin making use of tonal probability information after hearing only the onset and 40 ms of the vowel, primarily when hearing infrequent syllables. These findings demonstrate that the processing of suprasegmental information can be initiated with previously learned distributional knowledge until sufficient acoustic cues inform the listener of an incoming word.
Nonlinear, magnetics model of a synchronous generator

In support of full-electrification of aircraft and of aircraft design in general, detailed modeling of the aircraft electric generator is very useful. High-fidelity modeling of high-speed generators is necessary for the development of all-electric aircraft. Nonlinear magnetics play a significant role in the transient behavior of a synchronous machine (SM) generator during load on and load off cases. This paper demonstrates the nonlinear magnetics of an SM generator and nonlinear functions that accurately fit the magnetics.
Opening the Social: Sociological Imagination in Life Course Studies

The life course perspective originated with the recognition that an adequate understanding of “lives through time” requires attention to the importance of social context. Since those origins, extensive evidence of ways in which context shapes and organizes life course outcomes has been presented. Yet the problem of formulating an adequate theoretical understanding of context’s role in life course processes and outcomes persists, and remains unresolved. This paper suggests that life course scholarship, even while paying attention to context, has frequently relied on theoretical assumptions based in functionalism that restrict exploration of the full explanatory power of social forces. Contextual factors are “contained” through what we term a functional-developmental nexus. We illustrate this tension by examining three domains of life course inquiry: (1) a consideration of the place of agency in life course studies, (2) research on the early life influences on the life course and (3) the study of gene-environment interactions over the life course.
Reflections on the charmed circle

Cet article propose une critique et un commentaire du livre de Steven Wasserstrom, Religion apres religion, paru en 1999. Ce livre definit et circonscrit la tradition de l'histoire des religions en la dissociant d'autres developpements d'erudits du XIXe-debut XXe siecles habituellement consideres comme a l'origine de l'etude academique de la religion. Il remet ainsi en question les travaux et la notoriete d'historiens des religions tels que Gershom Scholem, Henry Corbin et Mircea Eliade.
Gliding resistance of extrasynovial and intrasynovial tendons through the A2 pulley.

The gliding ability of the flexor digitorum profundus tendon and of the palmaris longus tendon through the A2 pulley was compared, in terms of gliding resistance, with use of a system that we developed. Fourteen digits and the ipsilateral palmaris longus tendons from fourteen cadavera were used. The average gliding resistance at the interface between the palmaris longus tendon and the A2 pulley was found to be greater than that between the flexor digitorum profundus tendon and the A2 pulley under similar loading conditions. We concluded that the gliding ability of the palmaris longus tendon was inferior to that of the flexor digitorum profundus tendon in vitro. CLINICAL RELEVANCE: The findings of the present study are consistent with those of in vivo experiments in which extrasynovial tendon grafts have been associated with substantial formation of adhesions. The adhesions may be explained by the poor gliding ability of the palmaris longus tendon. The palmaris longus tendon may have limitations, because of gliding resistance, when it is used as a graft to reconstruct flexor tendons in the digits.
Acute Viral Hepatitis Treatment

Most people with acute viral hepatitis are anicteric and asymptomatic and infrequently seek medical attention. The physician therefore is more likely to see the patient with more severe disease that is clinically apparent. A safe and effective antiviral agent is not available although putative agents are being tested. Management of patients with viral hepatitis can be subdivided into several categories: acute uncomplicated viral hepatitis, cholestatic hepatitis, subacute fulminant hepatitis, and fulminant hepatitis.
Levers, Not Springs: How a Spearthrower Works and Why It Matters

A spearthrower, or atlatl, works as a lever to propel a light spear or dart, but there are still alternative theories about the mechanical principles. Howard proposed that atlatls work by extending the time force can be applied to a spear. Others suggest that the flex of the atlatl or the dart, or both, stores energy to propel the dart as from a spring. Both of these theories can be demonstrated to be wrong by a variety of evidence, including slow motion images. Those who believe that spearthrowers work by spring power often see them as ancestral to bows. Because they work by different principles, this is highly unlikely. Understanding how a spearthrower works is important in examining its capabilities and place in the evolution of technology, and both practical experimentation and theoretical understanding are necessary.
The Philosophical Basis of Eudaimonic Psychology

This chapter discusses the philosophical ideals animating eudaimonic psychology, arguing that eudaimonic measures of well-being reflect a reasonably coherent and defensible family of philosophical views centering on the notion of nature-fulfillment. Aristotelian theories are the best-known examples, but “eudaimonistic” views of well-being can take many forms, including the very different approach of John Stuart Mill. One goal of this chapter is to clarify the main theoretical options in this area, concerning the role of virtue in well-being; whether nature-fufillment is a matter of capacity-fulfillment or goal-fulfillment; and whether well-being is grounded entirely in the particulars of the individual’s makeup or in something else, such as species norms. A second goal is to defend eudaimonic measures, which are worth seeking regardless of our philosophical theories of well-being. The final part of the chapter sketches a “core schema for flourishing scales,” outlining the types of measures that will likely be most important to include in eudaimonic instruments, but leaving considerable room for variation. We can usefully think of the core eudaimonic insight in terms of this rough formula: happiness in a meaningful life that is rich in relationships and the free exercise of one’s capacities.
An integrated 0.5 mu m CMOS disposable TiN LDD/salicide spacer technology

A novel disposable TiN LDD/salicide spacer process has been developed for a 0.5- mu m CMOS technology. Both LDD (lightly doped drain) and salicide definition are obtained using a single disposable TiN spacer. This process results in CMOS devices with low salicided junction leakage, reduced source/drain lateral diffusion, and shallow phosphorus n- and boron p-regions for improved short-channel behavior. >
The Search for Accountability: United States v. McDonnell and the Fundamental Right to Honest Government

The U.S. Supreme Court in McDonnell v. United States (2016) vacated the conviction of a former Virginia governor for accepting bribes. The court found that arranging a meeting, calling or contacting another official, or hosting an event does not, by itself, rise to the level of an official act under the Hobbs Act and the mail and wire fraud statutes. This article argues that the Supreme Court’s decision in McDonnell v. United States will make it much more difficult for federal prosecutors to prosecute state and local governments for helping private individuals gain preferential access to government decision-makers at the state or local level. The article also argues that the decision will put pressure on state legislatures to significantly tighten state ethics laws to stop this type of conduct that reduces public trust in government.
Reducing Behavioral Health Inpatient Readmissions for People With Substance Use Disorders: Do Follow-Up Services Matter?

Objective:Individuals with substance use disorders are at high risk of hospital readmission. This study examined whether follow-up services received within 14 days of discharge from an inpatient hospital stay or residential detoxification reduced 90-day readmissions among Medicaid enrollees whose index admission included a substance use disorder diagnosis.Methods:Claims data were analyzed for Medicaid enrollees ages 18–64 with a substance use disorder diagnosis coded in any position for an inpatient hospital stay or residential detoxification in 2008 (N=30,439). Follow-up behavioral health services included residential, intensive outpatient, outpatient, and medication-assisted treatment (MAT). Analyses included data from ten states or fewer, based on a minimum number of index admissions and the availability of follow-up services or MAT. Survival analyses with time-varying independent variables were used to test the association of receipt of follow-up services and MAT with behavioral health readmissions.Re...
Weakening of SiSi bonding in exohydrogenated Si60 nanoclusters

Abstract We performed density functional theory (DFT) analyses of several hollow cage-like Si60 nanoclusters and found a favoring of exohydrogenation in terms of reduced binding energies in all the structures except the Si60 fullerene. Further investigation into the effects of exohydrogenation on the Si Si bonding network revealed a level of weakening in Si Si bonds. A correlation was established between the magnitude of this weakening and the success of exohydrogenation in stabilizing the nanocluster. In addition, we found a slightly bent chain of individual Si20 units to exhibit the lowest binding energy among the present group of Si60 clusters studied here.
BP Targets in CKD, Mortality, and SPRINT: What Have We Learned?

Control of hypertension has long been a fundamental part of the care for patients with CKD. The vast majority of patients with CKD develop disturbances in sodium balance and pressor mechanisms that lead to higher arterial pressures as GFR declines.[1][1] Higher BP interacts with both classic
Defining and measuring recovery from myalgic encephalomyelitis and chronic fatigue syndrome: the physician perspective

AbstractPurpose: To inform an operationalised definition of recovery from myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS) for research and practice. Without a consensus on defining and measuring recovery, there will continue to be controversy amongst researchers, clinicians, and patients when interpreting treatment outcomes.Method: This study explores physicians’ views on recovery from ME and CFS. We conducted semi-structured interviews with 10 physician participants who are experts in the ME and CFS field. Our deductive thematic analysis, using a realist perspective, provided a framework for differentiating recovery and significant improvement.Results: Physicians conceptualised recovery as complete symptom remission and a return to premorbid functioning (adjusted for with age), whereas they viewed significant improvement as a substantial reduction in symptoms with considerable functional gains, where patients may operate in daily life but still must cope or be treated.Conclusions: Our f...
The Variable Nature of News Media Influence

It is widely held in the social science community that the news media have little influence on public opinion. In this paper, it is argued that this counterintuitive belief is based on weak theorie...
Application of Adult Learning Theory to Physician Assistant Education.

AbstractJust as we depend on medical science and research to treat patients, we should connect our teaching methods to educational theory and research. In particular, the foundations of adult education philosophy and adult learning theories can be deliberately applied to further strengthen the clini
The Cognitive Study of Science

The aim of the cognitive study of science is to develop a cognitive theory of science. But what is meant by a ‘theory’ of science? And why do I call it ‘cognitive’?1
CausaLearn: Automated Framework for Scalable Streaming-based Causal Bayesian Learning using FPGAs

This paper proposes CausaLearn, the first automated framework that enables real-time and scalable approximation of Probability Density Function (PDF) in the context of causal Bayesian graphical models. CausaLearn targets complex streaming scenarios in which the input data evolves over time and independence cannot be assumed between data samples (e.g., continuous time-varying data analysis). Our framework is devised using a HW/SW co-design approach. We provide the first implementation of Hamiltonian Markov Chain Monte Carlo on FPGA that can efficiently sample from the steady state probability distribution at scales while considering the correlation between the observed data. CausaLearn is customizable to the limits of the underlying resource provisioning in order to maximize the effective system throughput. It uses physical profiling to abstract high-level hardware characteristics. These characteristics are integrated into our automated customization unit in order to tile, schedule, and batch the PDF approximation workload corresponding to the pertinent platform resources and constraints. We benchmark the design performance for analyzing various massive time-series data on three FPGA platforms with different computational budgets. Our extensive evaluations demonstrate up to two orders-of-magnitude runtime and energy improvements compared to the best-known prior solution. We provide an accompanying API that can be leveraged by data scientists and practitioners to automate and abstract hardware design optimization.
Influences and Impact of Anxiety and Depression in the Setting of Inflammatory Bowel Disease.

Background Individuals with inflammatory bowel disease (IBD) are at increased risk of developing anxiety or depression (A&D). Crohn's disease (CD) and ulcerative colitis (UC) with comorbid A&D are both more challenging to manage. IBD providers need to better understand the causes and impact of A&D in order to improve care for IBD patients. We sought to identify clinical factors that influence development of A&D and healthcare utilization in IBD. Methods This is a retrospective analysis using an IBD natural history registry from a single tertiary care referral center. Presence of A&D was determined based upon responses to the Hospital Anxiety and Depression Scale. Demographic and clinical factors were abstracted to evaluate for significant associations. Results Four hundred thirty-two IBD patients (132 UC, 256 CD, and 44 indeterminate colitis) were included in this study. One hundred ninety-two (44.4%) had anxiety or depression or both, and most were female (59.4%, P < 0.05). History of surgery (P < 0.05), female gender (P < 0.05), smoking (P < 0.05), and extra-intestinal manifestations (P < 0.01) were each independently predictive of A&D. Inflammatory bowel disease patients with A&D more often underwent imaging studies (53.6% vs 36.7%, P < 0.05), visited the ED (30.7% vs 20.8%, P < 0.05), or were hospitalized (31.7% vs 21.7%, P < 0.05). They were also more frequently prescribed corticosteroids (50.5% vs 36.7%, P < 0.01) and biologic medications (62.5% vs 51.3%, P < 0.05). Finally, they were more likely to have had at least 1 "no-show" (29.2% vs 16.7%, P < 0.01) and had a higher mean number of "no-shows" (0.69 +/- 0.1 vs 0.30 +/- 0.1, P < 0.01) over the study period. Discussion Anxiety and depression are common in the setting of IBD and are strongly associated with surgical history, disease complications (including extra-intestinal manifestations), smoking, and female gender. Inflammatory bowel disease patients with A&D are also more likely to require therapy and to utilize healthcare resources. This study refines our understanding of A&D development and its impact in IBD and provides additional considerations for management in this setting.
Abstract 2195: Temporal and spatial dynamics of metastatic colonization revealed by 26 rapid-autopsy tumor biopsies from a TNBC patient

Metastatic breast cancer is an advanced-stage disease in which the cancer cells have spread to distant organs. To understand the patterns of metastatic colonization in a patient who presented with aggressive disease, we have collected tumor biopsies at initial diagnosis, at mastectomy necessitated by the patient9s relapse, twenty-six metastatic tumors across seven organs and two normal tissue control skin biopsies via a rapid autopsy procedure within hours after the patient9s death. All biopsy samples were subjected to 60X Illumina whole genome sequencing. Our analysis revealed extensive chromosomal changes including amplifications, deletions, LOH and translocations, as well as known driver mutations in RB1, TP53, and PTEN in all tumor samples. We used the CNV and LOH data to reconstruct the phylogenetic relationships among the tumor samples. We used the somatic SNV allele frequencies in copy number-normal regions to refine these phylogenetic relationships, and to establish the evolution of the tumor at the subclonal level across different metastatic sites, with an extension of our SubcloneSeeker algorithm. Our analysis reveals the lung as the first metastatic site. In fact, this invasion occurred before relapse at the primary site in the breast, indicating early metastatic escape. This initial invasion was followed by distinct waves of massive metastatic expansion, beginning with the abdominal organs, then the lymph nodes, brain and bones. As the initial invasion, each metastatic wave involved other distinct sites in the lungs, these sites serving as incubators where subclones further evolved prior to seeding new metastatic sites. Finally, we see clear evidence for metastatic “recolonization” where such further evolved subclones invaded already established, earlier metastatic sites. The high number of biopsied sites in this study, 30 in all, allowed us to reconstruct the evolution of the aggressive disease in our patient with unprecedented resolution, and to identify characteristic patterns of metastatic colonization. If confirmed in additional, similarly high resolution datasets, these patterns will lead to better understanding of the metastatic process, and guide effective clinical intervention. Citation Format: Xiaomeng Huang, Yi Qiao, Samuel W. Brady, Adam Cohen, Andrea H. Bild, Gabor T. Marth. Temporal and spatial dynamics of metastatic colonization revealed by 26 rapid-autopsy tumor biopsies from a TNBC patient [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2195.
A data mining-based engineering design support system: a research agenda

Currently, designers do not have access to product life cycle information and other feedback, causing costly design iterations and increased time-to-market. Our research proposes using data mining to incorporate this heterogeneous and distributed information into the beginning stages of design — thereby reducing iterations and lowering the cost of product design.
Plasticity reveals hidden resistance to extinction under climate change in the global hotspot of salamander diversity

Extinction rates are predicted to rise exponentially under climate warming, but many of these predictions ignore physiological and behavioral plasticity that might buffer species from extinction. We evaluated the potential for physiological acclimatization and behavioral avoidance of poor climatic conditions to lower extinction risk under climate change in the global hotspot of salamander diversity, a region currently predicted to lose most of the salamander habitat due to warming. Our approach integrated experimental physiology and behavior into a mechanistic species distribution model to predict extinction risk based on an individual’s capacity to maintain energy balance with and without plasticity. We assessed the sensitivity of extinction risk to body size, behavioral strategies, limitations on energy intake, and physiological acclimatization of water loss and metabolic rate. The field and laboratory experiments indicated that salamanders readily acclimatize water loss rates and metabolic rates in ways that could maintain positive energy balance. Projections with plasticity reduced extinction risk by 72% under climate warming, especially in the core of their range. Further analyses revealed that juveniles might experience the greatest physiological stress under climate warming, but we identified specific physiological adaptations or plastic responses that could minimize the lethal physiological stress imposed on juveniles. We conclude that incorporating plasticity fundamentally alters ecological predictions under climate change by reducing extinction risk in the hotspot of salamander diversity.
The Pediatric Guideline Adherence and Outcomes (PEGASUS) programme in severe traumatic brain injury: a single-centre hybrid implementation and effectiveness study

Summary Background As far as we know, there are no tested in-hospital care programmes for paediatric traumatic brain injury. We aimed to assess implementation and effectiveness of the Pediatric Guideline Adherence and Outcomes (PEGASUS) programme in children with severe traumatic brain injury. Methods We did a prospective hybrid implementation and effectiveness study at the Harborview Medical Center (Seattle, WA, USA). We included children (aged 40 mm Hg) for 72 h after the diagnosis of severe traumatic brain injury. Poisson regression with robust standard errors was used to estimate the association between adhering to key performance indicators and discharge outcomes. Findings Between May 1, 2011, and July 1, 2017, 199 children (median age 11·9 years [IQR 3·4–16·1]) participated in the PEGASUS programme, of whom 193 (97%) had severe traumatic brain injury and six (3%) had moderate traumatic brain injury. 105 patients contributed data for all three key performance indicators. Adherence to at least one key performance indicator was achieved by 101 (96%) of 105 participants, and 44 (42%) achieved adherence to all three key performance indicators. Programme participants achieved adherence to the key performance indicators of hypocarbia (76 of 105 [72%]), nutrition (162 of 199 [81%]), and cerebral perfusion pressure (128 of 199 [64%]). Adherence to the nutrition key performance indicator was associated with higher discharge survival (relative risk [RR] 2·70, 95% CI 1·54–4·73) and a more favourable discharge disposition (3·05, 1·52–6·11). Adherence to the cerebral perfusion pressure key performance indicator was also associated with higher discharge survival (RR 1·33, 95% CI 1·12–1·59) and favourable disposition (1·53, 1·19–1·96). Adherence to each additional key performance indicator was associated with higher survival (RR 1·27, 1·12–1·44) and a more favourable discharge disposition (1·46, 1·23–1·72), in a dose-response manner. Interpretation The multilevel, hospital-wide, high-fidelity PEGASUS programme might benefit children and adolescents admitted to the emergency department with severe traumatic brain injury. Cerebral perfusion pressure, nutrition, and hypocarbia targets are essential components of the PEGASUS programme and are associated with favourable discharge outcomes. Funding National Institutes of Health.
The Unexpected Gift: “Oh, and You’ll be Responsible for the Model UN Program”

When you begin a job, you never know what assignments might open new doors; that was my experience when I became a Model UN faculty advisor. This chapter shares some of the many ways I have found to build onto the basic job of preparing students to participate in conferences each year. It’s been a foundation to stretch and grow. It has kept me energized and excited even when other responsibilities were less inspiring. It’s a pleasure to devote my energy to an endeavor that matters. My contacts with alumni constantly reinforce what an amazing experience Model UN is for the students. As I reflect on my years with these students, I recognize that I have been transformed through leading Model UN as much as my students have been transformed by participating.
SDF-1 and its receptor, CXCR4, are down-regulated by the AHR ligand, 3,3-diindolylmethane, in breast and ovarian cancer cells

Proc Amer Assoc Cancer Res, Volume 47, 2006 4681 Cruciferous vegetables are thought to be protective for numerous types of cancer. 3,3’-diindolylmethane (DIM), an acid-catalyzed product generated in the consumption of cruciferous vegetables, appears to be chemoprotective, as it has been found to reduce the incidence of spontaneous and carcinogen-induced tumors in rodents, including those of the breast. Although DIM is a ligand for the AHR, it appears to exhibit little or no toxicity, and is being pursued as a potential chemopreventative and chemotherapeutic agent for breast cancer. The CXCR4/SDF-1 axis is known to play a central role in the metastasis of breast cancer, and is thought to play a role in ovarian cancer as well. Organs to which these cancers metastasize secrete the SDF-1 ligand, which binds to CXCR4 expressed on the primary cancer cells. This subsequently stimulates their invasive properties as well as attracts them to the organ sites of metastasis. Interestingly, SDF-1 is also expressed in primary breast and ovarian cancer cells and appears to stimulate proliferation through an autocrine mechanism. Using real-time quantitative PCR, flow cytometry, and ELISA, we found that DIM down-regulates CXCR4 in the ER+ breast cancer cell line, MCF-7, as well as in the ER-, metastatic breast cancer cell line, MB-MDA-231. We also show that DIM down-regulates both CXCR4 and SDF-1 in the invasive ovarian cancer cell line, BG-1, in a dose-responsive manner. Our data suggest that one mechanism whereby DIM protects against cancer is through the repression of SDF-1 and/or CXCR4, thereby lowering the invasive and metastatic potential of these cells.
Emerging role of long non-coding RNAs in cancer precision medicine.

A vast majority of the human genome encodes long non-coding RNAs (lncRNAs) as compared to protein-coding genes (PCGs). But most efforts to determine biomarkers of anticancer drug response have focu...
Multiple myeloma masquerading as medication-related osteonecrosis of the jaw: a case study

Background Bisphosphonates, such as zoledronic acid, are commonly used to treat bone metastasis from malignant conditions, such as multiple myeloma, or from solid tumors, such as breast or prostate cancer. Medication-related osteonecrosis of the jaw (MRONJ) is one of the complications of bisphosphonate treatment. The reported incidence of MRONJ among patients with cancers and bone metastases treated with zoledronic acid is 1.3%. MRONJ has been reported to have an incidence rate of up to 18.5%. The clinical and radiographic presentations of MRONJ are very similar to those of bone metastases, making early diagnosis and timely treatment challenging. This is a case report of a patient with multiple myeloma with a history of treatment with zoledronic acid and whose initial presentation of an intraoral lesion made it challenging to distinguish between bone metastasis and MRONJ. Case Summary This is a case report of a 67-year-old female with multiple myeloma, with a history of zoledronic acid, 28 doses taken from 2013 to 2016 and the disease in remission. The patient initially presented with a 1-week history of firm gingival swelling buccal and lingual to a fixed partial denture (FPD) in the left mandible. Panoramic radiography showed a well-defined radiolucent lesion. Considering her history of antiresorptive treatment, MRONJ was considered as one of the diagnoses. However, because of the unusual hyperkeratotic nature of the buccal gingiva, relapsed disease was included in the differential diagnosis. Because of the unconventional clinical manifestation and concerns about relapsed disease, computed tomography guided bone biopsy was performed, and it revealed plasma cell neoplasm and necrotic bone. The patient was treated with palliative radiation therapy and antibiotics, which resulted in a significant decrease in her symptoms. Eventually, a portion of the FPD was removed, and an exposed bony site with a mobile bony sequestrum was revealed. Removal of the sequestrum led to complete gingival healing of the exposed site. Conclusions Maxillofacial manifestation of bone metastasis is common but is often overlooked. Therefore, it should be considered in the differential diagnosis when a patient with a history of antiresorptive medications presents with a gingival mass and/or exophytic bone. Good clinical judgment and well-timed bone biopsy and diagnostic imaging can lead to the correct diagnosis and optimal treatment.
Indoor air pollution and respiratory health effects in inner city children with moderate to severe asthma

Indoor air pollution is increasingly recognized as a significant risk for respiratory illness, particularly in vulnerable populations. Thirty-six children aged 6–14 years with moderate/severe asthma from inner city areas in New York City were studied for 2-week periods (summer and winter) using diaries and spirometry. Seven-day integrated indoor samples of PM10, PM2.5, trace elements, elemental/organic carbon, black carbon, and criteria gases (NO2, SO2, and O3) were collected in the subjects’ residences. Asthma outcomes included cough and wheeze severity, albuterol use, and pulmonary function. Mixed effects regression models for longitudinal data were used to relate weekly indoor pollutant concentrations to asthma outcomes. Odds ratios (ORs) were calculated for ordinal outcomes. During winter, significant positive associations for average weekly symptom severity scores were seen for NO2 (OR = 2.83; p = 0.02), calcium (OR = 3.29; p = 0.02), and silicon (OR = 3.64; p = 0.04). In summer, chlorine was associated with average weekly symptom scores (OR = 1.85; p = 0.004). Average albuterol puff use per day in winter was associated with NO2 (OR = 5.89; p = 0.009), nickel (OR = 2.27; p = 0.05), and silicon (OR = 5.59; p = 0.05). Albuterol use was not associated with indoor pollutants in summer. Asthma severity was associated with specific indoor pollutants. Seasonal differences were observed by pollutant and by clinical index studied.
Organic barley producers' desired qualities for crop improvement

Barley fits well into many different organic farming systems. It can be grown as either a winter or spring annual crop in many temperate regions. Barley can be used for food, malting, or animal feed, providing growers with diverse marketing opportunities. Despite its advantages, many organic farmers in the USA have not adopted barley as a regular crop in their rotation. Researchers surveyed organic barley producers to discover what they considered to be the main obstacles to growing barley. The primary obstacles identified were limited markets and price. Breeding and development of high-quality barley suitable for organic systems and specialty markets may be a way to expand markets and secure a better price. Farmers identified yield as the most important agronomic trait of interest, but other traits such as nutritional quality were also highly ranked. Naked (hull-less) barley bred for multi-use quality is a possible alternative that allows organic farmers to sell into multiple markets. Most respondents expressed interest in the development of such varieties suitable for organic farming conditions. The researchers conducted follow-up interviews to obtain detailed information on how barley is used in organic farming systems, production practices, costs of production, and what traits farmers would like to see breeders focus on.