cssi/SciSciGPT-SciSciNet huggingface dataset:
A method for registration of single photon emission computed tomography (SPECT) and computed tomography (CT) images for liver stereotactic radiotherapy (SRT).

Purpose: To describe a simple method of coregistration of nonanatomic liver SPECT and CT images acquired in separate sessions for three-dimensional (3D)-CRT planning utilizing dual radiolabeled and radiopaque body surface markers, and evaluate the accuracy of the registration on the patient surface. Methods: Ten patients treated for liver metastases or hepatocellular carcinoma with stereotactic body radiation therapy or 3D-CRT were selected for this study to evaluate the SPECT/CT registration process. All patients were positioned in a custom-molded vacuum bag on the flat table top. Nine radiopaque markers were taped to the abdominal surface in three axial planes at the level of the liver. Following CT imaging, the nine radiopaque markers were then labeled with radioactive tags, each containing 10μCi of 99mTc, and SPECT images were acquired. The metric used to evaluate the registration was the fiducial registration error (FRE), defined as the root mean square of the distance between pairs of homologous markers on the CT and SPECT images. The evaluation of the registration accuracy was performed in two steps: first the minimum number of markers necessary to obtain a robust registration was optimized; second the FRE was calculated on the remaining set of unused markers. Additionally, the deformation of the patientˈs abdominal surface between CT and SPECT acquisition sessions was evaluated using the distances between all possible unused marker pairs on the CT and SPECT images separately. The root mean square of the CT-to-SPECT difference between those distances was used to define the deformation index (DI). The registration method was evaluated on all ten patients in addition to an anthropomorphic phantom study. Results: The minimum number of markers above which the registration was not improved by more than 1 mm was 4. The FRE, calculated over the 5 remaining markers, was 6.1 mm for the patient population and 1.8 mm for the phantom study. The DI was 5.0 mm on average over all 10 patients and correlated well with the FRE. The DI was 1.6 mm for the phantom study, which represented the imaging systems’ resolution and the ability to place the CT and SPECT markers at the exact same location. Conclusions: It is feasible to use radiolabeled and radiopaque dual body surface markers for registration of SPECT and CT images acquired in separate sessions allowing conformal avoidance of SPECT-defined functional normal liver. Point-based rigid registration accuracy on the patient surface of 6.1 mm can be achieved using 4 dual body surface markers. The main contribution to the registration error is the deformation of the abdominal surface, arising from the inability to setup the patient in the exact same position at different times on two different imaging systems, and to properly account for breathing artifacts on the CT and SPECT images.
Using Known Occurrences to Model Suitable Habitat for a Rare Forest Type in West Virginia Under Select Climate Change Scenarios

Many studies now identify the impacts of global climate change as a conservation threat to terrestrial ecosystems. In West Virginia, red spruce ( Picea rubens ) forests are a rare forest community of great ecological value, occurring in ‘island-like’ distributions among higher elevations. In this study, 168 red spruce presence localities and 24 environmental and site-specific variables were used to model red spruce habitat using select climate change scenarios. Maximum entropy models were created for aggressive and conservative climate change scenarios, with each scenario model performed for three time periods (i.e., 2020, 2050, and 2080). Results for both model analyses identified three variables which contributed significantly to model performance: mean temperature of the coldest quarter of the year, elevation, and minimum temperature of the coldest month of the year. Changes in suitable habitat area were also assessed for both model scenarios at each time period examined. Approximately 6.2% of the land area in West Virginia was modeled under current habitat conditions as suitable red spruce habitat. However, by the time period 2020, a loss of 78% and 52% was identified for the aggressive and conservative climate change models, respectively. By the time period 2080, no suitable red spruce habitat was modeled using the aggressive climate change scenario with an 85% reduction in current modeled habitat identified using the conservative model. These findings indicate the potential impacts of climate change on red spruce forest habitat in West Virginia and provide valuable guidance for future restoration efforts by identifying areas most likely to succeed under altered climatic conditions.
The Social Dynamics of Cigarette Smoking: A Family Systems Perspective

This paper uses family systems concepts and the Family FIRO model to show how cigarette smoking occurs in the context of the important relationships in a smoker's life. Specifically, smoking is viewed as a way a person is included in relationships, is in control in relationships, and perhaps is intimate in relationships. When smoking is well-established in the relationship, predictable interaction patterns surround it. When a person tries to quit or succeeds in quitting, these patterns change and may need to be replaced by nonsmoking alternatives. Partners may respond with support and willingness to create alternative patterns, or with undermining behavior stemming from a perceived threat to the established patterns. The model is offered for its heuristic value in guiding research and clinical experimentation. The paper also describes implications for family therapists as consultants to smoking-cessation programs.
Case-control study of student-perpetrated physical violence against educators.

PURPOSE: Although prior research focused primarily on student-on-student school violence, educators are also at risk. This study was designed to identify risk factors for assaults against educators. METHODS: Kindergarten-grade 12 educators (n = 26,000), randomly selected from a state license database, were screened for eligibility (6,469, eligible) by mailed questionnaire. Phase 1 (12-month recall) identified eligible assault cases (n = 372) and controls (n = 1,116), June 2004 to December 2005; phase 2 (case-control study; response, 78%) enabled identification of exposures through 1-month recall before student-perpetrated assaults (cases) and randomly selected months (controls). Directed acyclic graphs enabled confounder selection for multivariable logistic regression analyses; reweighting adjusted for potential biases. RESULTS: Risks (odds ratios, 95% confidence intervals) increased for working in: Special Education (5.84; 4.07-8.39) and School Social Work (7.18; 2.72-18.91); kindergarten to second grade (1.81; 1.18-2.77); urban (1.95; 1.38-2.76) schools; schools with less than 50 (8.40; 3.12-22.63), 50-200 (3.67; 1.84-7.34), 201-500 (2.09; 1.32-3.29), and 501-1000 (1.94; 1.25-3.01) students versus more than 1000; schools with inadequate resources always/frequently (1.62; 1.05-2.48) versus infrequently/never; inadequate building safety always/frequently (4.48; 2.54-7.90) versus infrequently/never; and environments with physical barriers (1.50; 1.07-2.10). Risks decreased with routine locker searches (0.49; 0.29-0.85) and accessible exits (0.36; 0.17-0.74). CONCLUSIONS: Identification of assault risk factors provides a basis for further investigation and interventions. Language: en
Removing the irregular frequencies from integral equations in wave-body interactions

The paper presents a method that removes the effects of all irregular frequencies in boundary-integral equations governing the interaction of regular waves with floating bodies of general geometry. A modified integral equation is obtained by the linear superposition of the classical Green equation and its normal derivative with respect to the field point.
An ultrasonic method to measure effective temperature in the vicinity of laser-induced optical breakdown

Laser-induced optical breakdown (LIOB) can be used to target microbubbles in tissue for biomedical applications. We have previously developed a system in which high-frequency (50 MHz) ultrasound is used to characterize LIOB in real time. By exploiting the relationship between sound speed and temperature in a medium, this system readily lends itself to temperature measurement in the vicinity of LIOB. Experiments were performed in which an LIOB bubble was created at the bottom of a water tank using a regeneratively amplified Ti:Sapphire laser. During and after laser exposure, a series of ultrasound pulse-echo signals was recorded to monitor arrival time shifts of reflections from the tank bottom in the region surrounding the bubble. A finite-element model was developed using commercial software (FEMLAB; Comsol Inc.). Predicted shifts in pulse-echo arrival time were calculated from the model data and compared with the experimentally measured shifts. The effective heat input in the model was varied and the mean squared error between model and experiment was minimized to determine the experimental heat input. Results suggest that, by adjusting laser parameters, LIOB can be controlled to be a thermally noninvasive process, producing only a small temperature change in the vicinity of the generated bubble.
Context dependent state tying for speech recognition using deep neural network acoustic models

This paper proposes an algorithm to design a tied-state inventory for a context dependent, neural network-based acoustic model for speech recognition. Rather than relying on a GMM/HMM system that operates on a different feature space and is of a different model family, the proposed algorithm optimizes state tying on the activation vectors of the neural network directly. Experiments show the viability of the proposed algorithm reducing the WER from 36.3% for a context independent system to 16.0% for a 15000 tied-state system.
The National and Local Significance of Wyatt's Rebellion in Surrey

Though much has been written about Wyatt's rebellion, it remains controversial. There is, first of all, lively debate about the rebels' motives in rising against Mary Tudor in January and February 1554. It is generally agreed that some rebels wished only to force changes in royal policy, while others sought to replace the queen with her sister Elizabeth and Edward Courtenay, the earl of Devon. But, while D. M. Loades and his adherents contend that the rising was caused almost entirely by opposition to Mary's proposed marriage to Prince Philip of Spain, others argue – to varying degrees – that religion was significant and that many rebels were protestants seeking to thwart a catholic restoration.
Design as you see FIT: system-level soft error analysis of sequential circuits

Soft errors in combinational and sequential elements of digital circuits are an increasing concern as a result of technology scaling. Several techniques for gate and latch hardening have been proposed to synthesize circuits that are tolerant to soft errors. However, each such technique has associated overheads of power, area, and performance. In this paper, we present a new methodology to compute the failures in time (FIT) rate of a sequential circuit where the failures are at the system-level. System-level failures are detected by monitors derived from functional specifications. Our approach includes efficient methods to compute the FIT rate of combinational circuits (CFIT), incorporating effects of logical, timing, and electrical masking. The contribution of circuit components to the FIT rate of the overall circuit can be computed from the CFIT and probabilities of system-level failure due to soft errors in those elements. Designers can use this information to perform Pareto-optimal hardening of selected sequential and combinational components against soft errors. We present experimental results demonstrating that our analysis is efficient, accurate, and provides data that can be used to synthesize a low-overhead, low-FIT sequential circuit.
The Logic of Choice

The choice construct (choose x: φ(x)) is useful in software specifications. We study extensions of first-order logic with the choice construct. We prove some results about Hilbert's e operator, but in the main part of the paper we consider the case when all choices are independent.
Nature of creative analogies in biologically inspired innovative design

Analogy is a fundamental process of creativity. Biologically inspired design by definition entails cross-domain analogies, and in practice has led to many innovative designs. Thus, biological inspired design is an ideal domain for studying creative analogies. In this paper, we describe an intricate episode of biologically inspired design that unfolded over an extended period of time. We then analyze the episode in terms of Why, What, How and When questions of analogy. This analysis provides a content theory of creative analogies in biologically inspired design.
Application of normalization method to fracture resistance testing for storage tank A285 carbon steel

Abstract To determine the fracture resistance and its constraint effect for storage tank A285 carbon steel, a set of single edge notched bend (SENB) specimens with different crack lengths are tested under the guideline of ASTM standard E1820. Normalization method is adopted to develop J–R curves by directly using the load versus load-line displacement data without the need for online crack size measurement. For validation, the conventional electric potential drop method is also used to monitor crack extension, and to determine the J–R curves. The results indicate that the crack extension, J–R curves and fracture initiation toughness determined from both methods are nearly identical for the SENB specimens considered. The J–R curves obtained from the A285 SENB specimens show a strong dependence on crack size or fracture constraint. In reference to the J–A 2 fracture theory, the constraint effect is quantified by a constraint parameter A 2 . Through experimental and numerical analyses of the specimens, a constraint-corrected J–R curve is obtained as a function of crack extension and the constraint parameter A 2 . It is concluded that the normalization method is valid and cost-effective for the determination of J–R curves from both standard and nonstandard SENB specimens. In addition, the parameter A 2 can reasonably quantify the constraint effect on the experimental J–R curves.
The relationship between illegal behaviors and borderline personality symptoms among internal medicine outpatients.

Abstract Background In psychiatric dysfunction, illegal behaviors are frequently associated with the traditional prison personality antisocial personality disorder. However, some empirical data indicate that illegal behaviors may also be associated with borderline personality, which is the focus of the present study. Method Using a cross-sectional sample of consecutive internal medicine outpatients from a resident-provider clinic, we examined relationships between 27 illegal behaviors as delineated by the Federal Bureau of Investigation's crime-cataloguing schema and 2 measures of borderline personality disorder (BPD), the BPD scale of the Personality Diagnostic Questionnaire-4 and the Self-Harm Inventory. Results The overall correlations between BPD and the number of the 27 illegal behaviors endorsed were r = 0.32 (P Conclusions There appear to be associations between illegal behaviors and BPD, particularly in relation to alcohol/substance abuse and in young men.
FROM SOCIAL DOCTRINE TO IMPLEMENTATION: AGENDA SETTING IN COMPARABLE WORTH

Comparable worth is a policy issue with twofaces. It is both a social doctrine proposing equal pay for work of comparable value and a methodology in personnel administration, called “objective job evaluation,” that introduces new evaluative criteria to assess job worth. It has achieved policy status on the subnational level through the use of multiple agenda setting and implementation strategies by coalitions of women's advocacy groups and unions. The shifting use of comparable worth as a social doctrine or as a methodology to assess jobs has varied with the distribution of power resources of the sponsors and the receptiveness of the policy setting. The paper explores how comparable worth developed as a general policy issue on the subnational level. It offers a policy framework to interpret i t s transformation into policies and programs and assesses i t s probable impact on personnel administration.
Changes over Time in the ADL Status of Elderly US Veterans

The ageing of the US veteran population has greatly out-paced that of the general US population in the last decade and the demographics of this subgroup have changed relative to the US general population. To address the concerns of policy makers within the US Department of Veterans' Affairs (VA), data on elderly US male veterans and non-veterans from the Longitudinal Survey on Aging in 1984, 1986, 1988, and 1990 were used in a prospective study. Health status or well-being was assessed through changes over time in ADL status, according to the following five categories; (I) the presence of no ADL dependence and not developing a dependence between survey periods, (II) no change in ADL dependence between survey periods, (III) an increase in ADL dependence status between survey periods, (IV) a decrease in ADL dependence between survey periods, and (V) the occurrence of death between survey periods. Using a polytomous logistic regression model, these five categories were assessed in relation to a set of variables representing social, health-care utilization, and socioeconomic characteristics. The estimated coefficients from the model indicate that family income, having worked in the last 12 months, having an increase or no change in levels of physical activity in the past 12 months and the presence of Medicare coverage are inversely associated with moving, over time, into a lower state of health status or well-being. The prior existence of an ADL limitation, the number of doctor and hospital visits in the past 12 months, level of education, having been widowed in the past 12 months and veteran status were all proportionally associated with the likelihood of moving into a lower state of health status or well-being. These findings lead to the conclusion that being a veteran in the US does make a difference in regard to moving into various states of health status or well-being. This difference is supported by the estimated coefficient for veteran status being significant at a p value of 0.01 and through an evaluation of the estimated transition likelihood, controlling for veteran status. Veterans are less likely to die than their non-veteran counterparts, but have a greater likelihood of transition into levels of ADL dependence. Similarly, given the existence of a prior ADL limitation, over time, veterans are less likely to die, but more likely to move into a state of increased ADL limitations.
Noise in active resonators and the available dynamic range

Active resonators used to make bandpass filters are shown to suffer from a fundamental deterioration in available dynamic range with increasing Q, which is shown to arise from the dissipation in the transistors simulating inductance or performing an equivalent function. An active resonator with Q>1 may only attain a specified dynamic range with the use of a larger tuning capacitance than its passive counterpart, and with a consequent larger lower dissipation at a given frequency of operation. This poses a serious limitation on the integrated circuit realization of high-frequency filters with high-Q poles. >
Variational principles, Lie point symmetries, and similarity solutions of the vector Maxwell equations in non-linear optics

Abstract The vector Maxwell equations of non-linear optics coupled to a single Lorentz oscillator and with instantaneous Kerr non-linearity are investigated by using Lie symmetry group methods. Lagrangian and Hamiltonian formulations of the equations are obtained. The aim of the analysis is to explore the properties of Maxwell’s equations in non-linear optics, without resorting to the commonly used non-linear Schrodinger (NLS) equation approximation in which a high frequency carrier wave is modulated on long length and time scales due to non-linear sideband wave interactions. This is important in femto-second pulse propagation in which the NLS approximation is expected to break down. The canonical Hamiltonian description of the equations involves the solution of a polynomial equation for the electric field E, in terms of the canonical variables, with possible multiple real roots for E. In order to circumvent this problem, non-canonical Poisson bracket formulations of the equations are obtained in which the electric field is one of the non-canonical variables. Noether’s theorem, and the Lie point symmetries admitted by the equations are used to obtain four conservation laws, including the electromagnetic momentum and energy conservation laws, corresponding to the space and time translation invariance symmetries. The symmetries are used to obtain classical similarity solutions of the equations. The traveling wave similarity solutions for the case of a cubic Kerr non-linearity, are shown to reduce to a single ordinary differential equation for the variable y = E 2 , where E is the electric field intensity. The differential equation has solutions y = y ( ξ ), where ξ = z − st is the traveling wave variable and s is the velocity of the wave. These solutions exhibit new phenomena not obtainable by the NLS approximation. The characteristics of the solutions depends on the values of the wave velocity s and the energy integration constant ϵ . Both smooth periodic traveling waves and non-smooth solutions in which the electric field gradient diverges (i.e. solutions in which | E ξ |→∞ at specific values of E, but where | E | is bounded) are obtained. The traveling wave solutions also include a kink-type solution, with possible important applications in femto-second technology.
NEW TYPE OF TUNNEL TANK REPLACES DAY TANK1

Current retail distribution methods compel the glass manufacturer to be prepared for rapid changes in style, designs, and colors. Small, flexible, producing units capable of accurate control and permitting rapid color changes or composition of glass aid in maintaining a close ratio between production and current sales. Day tanks are elastic in operation, but are not as economical or reliable as continuous tanks. A day tank was replaced with a tunnel tank (two feet wide by twenty feet long) of equivalent melting capacity per shift. Details of construction, drawing, gas consumption, filling, and operation are given. Advantages gained: dependable production with uniform color, melting conditions stabilized and assurred, producing capacity increased threefold without increasing fuel or labor costs, repair production loss cut, repair labor and material costs reduced.
The Impact of Obesity on Breast Cancer: A Retrospective Review

Background Obesity has been linked to many adverse health consequences, including breast cancer; however, the impact on clinical presentation, tumor characteristics, and survival outcomes has yet to be clearly defined.
Laying the Groundwork for a Large-Scale Spent Nuclear Fuel Transportation System

The US Department of Energy Office of Nuclear Energy established the Nuclear Fuels Storage and Transportation Planning Project (NFST) to lay the groundwork for implementing interim storage of commercial spent nuclear fuel (SNF), including associated transportation activities. Progress is being made on long lead time, destination-independent aspects of the SNF transportation system in three areas:• Institutional: stakeholder interactions needed for system success, including development of a transportation plan, policy development to implement Nuclear Waste Policy Act Section 180(c), and identification of a preliminary suite of national transportation routes based on regulatory requirements and coordination with stakeholders with diverse interests.• Operational: activities required to run a large-scale transportation system; focus is on development of a new routing analysis tool, study of infrastructure near storage sites that may be de-inventoried first, and development of tools for modeling transportation activities.• Hardware: casks, railcars, and other items necessary to operate the system. Activities are primarily focused on development of railcars compliant with Association of American Railroads Standard S-2043 and studies on the use of rail casks and their ancillary equipment.NFST is making significant progress in all of these areas for a future transportation system to transport SNF from commercial reactors.Copyright © 2015 by ASME
Nonutilization of Statins in a Community-based Population with a History of Coronary Revascularization

Abstract Purpose Statin therapy has been reported to reduce the incidence of vascular events in patients with atherosclerosis, but adherence to statins may be suboptimal. The aims of this study were to quantify the rate of statin use among individuals with a history of coronary revascularization in a large, integrated health care system and to determine which demographic characteristics and clinical factors are associated with statin use. Methods This was a retrospective cohort study using database programming and chart review. The study included adult members of Kaiser Permanente Northern California with a history of coronary revascularization. The study outcome was off-statin status, defined as a ≥1-year gap between filled prescriptions. The predictor variables included age, race, body mass index, dyslipidemia, liver disease, kidney disease, and history of statin allergy. Multivariable logistic regression was used to quantify the associations between the predictor variables and statin status. A chart review of a randomly selected subset was performed to identify reasons why individuals were not taking statins. Findings The study population included 17,869 Kaiser Permanente Northern California members, of which 18.3% had off-statin status. The following variables were associated with off-statin status: statin allergy (odds ratio [OR] = 2.18; 95% CI, 1.89−2.52), end-stage renal disease (OR = 1.55; 95% CI, 1.26−1.91), liver disease (OR = 1.44; 95% CI, 1.08−1.93), African-American race (OR = 1.55 vs white; 95% CI, 1.32−1.81), and Latino race (OR = 1.18; 95% CI, 1.05−1.33). The chart review found that off-statin status typically reflects patient (79%) rather than provider (21%) preference. Implications A significant minority of patients with a history of coronary revascularization are not taking statins. Off-statin status is associated with kidney disease, liver disease, African-American race, and Latino race. At an individual level, off-statin status was usually driven by patient preference, due to minor or undefined reasons. These findings may be useful in guiding strategies to increase statin use in individuals with atherosclerosis.
Characterization of Metabolic Pathways in Breast Cancer using Diffuse Optical Tomography

Diffuse Optical Tomography measured physiological parameters were compared to pathological properties of breast cancer including Ki67 expression level. The Warburg effect was observed, which indicates a metabolic pathway taken by the cancer.
THE ENEMY WITHIN

![Figure][1] In energy metabolism, there are two means of ATP production: glycolysis and oxidative phosphorylation in mitochondria. The fact that mitochondria produce roughly 15 times more ATP per mole of glucose than glycolysis usually makes them the ideal choice for ATP production. However
State-Local Relations in Policy Implementation: The Case of Highway Transportation in Iowa

This article examines relationships between state agencies and local communities, using survey and interview data from a case study of the Iowa Department of Transportation. It argues that these relationships often parallel the agency-clientele relationships observed by public administration scholars. The agency derives similar benefits from local government support as from private clientele support, namely, an independent power base that helps to preserve its flow of resources and its administrative autonomy. IDOTpossesses formidable political resources in the breadth and intensity of its clientele, but the key to IDOT's success is the skillful utilization of those resources through an administrative strategy stressing the development of widely accepted technical decision-criteria and an administrative style emphasizing accessibility, responsiveness, and flexibility. A survey of mayors and local business leaders shows that this strategy has generated widespread positive perceptions of the department among these clientele groups.
Anticonvulsant doses of inosine result in brain levels sufficient to inhibit [3H] diazepam binding.

Several purines have been shown to be competitive inhibitors of [3H] diazepam binding. Inosine has also been shown to have benzodiazepine-like neurophysiologic, pharmacologic and behavioral effects, and to partially inhibit caffeine-induced seizures in mice. Using presumptive therapeutic doses of inosine, levels were determined in mouse brain at various times following injection. Inosine and hypoxanthine concentrations in brain increased several fold following inosine administration, indicating that inosine permeated the blood-brain barrier. The levels of inosine and hypoxanthine attained in brain were sufficient to inhibit by more than 50% the GABA-stimulated [3H] diazepam binding. These data suggest that that the anticonvulsant properties of inosine are related to its interaction with the benzodiazepine receptor.
Squamous Cell Carcinoma In Situ Overlying Merkel Cell Carcinoma.

Background Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous neoplasm that has exhibited an exponential increase in incidence in the past 3 decades. Combined MCC and cutaneous squamous cell carcinoma (SCC/MCC) is an uncommon variant of MCC that exhibits worse prognosis than pure MCC. Objective To describe the clinical presentation, dermoscopy, and histology of an unusual subtype of combined SCC/MCC. Methods and results A 73-year-old white woman presented with an ulcerated and violaceous 10-mm plaque on her right jawline that had been present for 2 to 3 months. On dermoscopy, the lesion was predominantly milky pink to red with peripheral crusting and large-caliber polymorphous vessels. Histology revealed SCC in situ above and adjacent to MCC. The tumor was excised with clear margins, and sentinel lymph node scintography was negative for nodal involvement.
Research in Technological Framework of 3D Morphological Virtual Simulation of Plant

Digital and visible expression of structure and biological attribute for plant are important research issues in modern agriculture,and study of digital plant is worthy for both theoretical researches and applications.A framework of technological framework for digital plant was introduced based on relations of data-knowledge-model in following aspects:data collection,3D virtual modeling,virtual scene rendering,and interactive applications.Some key technologies were discussed.Main theories and applications in modern digital agriculture were summarized and analyzed,and the developments in future were discussed.In order to provide references for development of virtual agriculture and digital agriculture,several key problems and solutions of digital plant 3D shape simulation were introduced as emphasis.
22 STROMELYSIN-1 5A/6A AND eNOS T-786C POLYMORPHISMS, MTHFR C677T-A1298C COMPOUND HETEROZYGOSITY, AND CIGARETTE-CANNABIS SMOKING: GENE-ENVIRONMENT PATHOPHYSIOLOGICAL ASSOCIATIONS WITH BUERGER'S DISEASE

In a 26-year-old white male with Buerger9s disease we hypothesized that gene polymorphisms which confer susceptibility to arterial spasm (stromelysin-1 5A/6A, eNOS T-786C) and C677T-A1298C MTHFR compound heterozygosity with decreased bioavailability of nitric oxide (NO) interacted with cigarette-cannabis smoking, as gene-environment interactive etiologies for the peripheral artery spasm, thrombosis, and arterial occlusion of Buerger9s disease. In a 26-year-old male who had heavily smoked cigarettes-cannabis, Buerger9s disease with rapid progression of bilateral lower limb gangrenous ischemia and intractable ischemic pain on rest despite smoking cessation threatened high above-knee amputations. There was complete arterial occlusion at the level of the left popliteal trifurcation. After documentation of thrombophilic C677T-A1298C compound MTHFR heterozygosity, folic acid 5 mg, vitamin B6 100 mg, and vitamin B12 2000 μg/day were started to optimize homocysteine metabolism and to reduce asymmetric dimethylarginine (ADMA) levels, an endogenous inhibitor of NO synthase. L-Arginine (15 g/day) was given as an approach to increase vasodilatory NO production via endothelial NO synthase (eNOS). Within 8 weeks on therapy, gangrenous ulcers on the right foot and leg healed, pain subsided, and peripheral arterial pulses normalized. Previously existing gangrene of the left great toe and second toe became complicated with cellulitis, necessitating below knee amputation. Healing was subsequently uneventful with bilateral normal peripheral arterial pulses. PCR analyses revealed heterozygosity for stromelysin-1 5A/6A and eNOS T-786C polymorphisms, previously shown to confer susceptibility to coronary artery spasm and myocardial infarction in synergy with cigarette smoking. In cigarette-cannabis smokers, we speculate that the development and severity of Buerger9s disease are related to a gene-environment interaction in subjects heterozygous for the stromelysin-1 5A/6A and eNOS T-786C polymorphisms, as well as C677T-A1298C MTHFR compound heterozygosity, which altogether reduce endogenous NO-mediated vasodilatation. In such cases, Buerger9s disease can successfully be treated by increasing NO production by giving oral L-arginine (15 g/day) while also optimizing homocysteine metabolism by provision of folic acid (5 mg), vitamin B6 (100 mg), and vitamin B12 (2000 μg)/day.
Joining in, interpretative reproduction, and transformations of occupations: What is “know-how” anyway?

ABSTRACTTo understand the early emergence of occupations, this paper suggests occupational scientists need to look for the little things infants do to participate in routine occupations of the people around them. This participation creates an interpersonal workspace where infants’ behaviors reflect the caregiving practices of the culture they were born into. Empirical research supports the idea that infants experience the action of people as intentional. Furthermore, when infants are actively engaged in doing things, this experience primes the infant to attend more to others doing the same thing. Though limited by physical immaturity, infants’ intentional coordination of action suggests a growing understanding of how to act. An embodied understanding of infants reflects their emotional responses so early participation is something they strive to do.
Variation and Versatility in Macroevolution

Publisher Summary Studies of macroevolutionary change are uniquely focused on events and processes that require time, including events that occur infrequently (or just once), or processes that are long in duration. With respect to phenotypic variation, macroevolution is typically the domain of large differences (whose study in aggregate becomes the study of disparity), of the origin of novelties (features that do not correspond to characters or structures present in an ancestor), or of differences (of whatever magnitude or character) that are associated with taxonomic diversification. For variation to be observed, it must not only have been produced but also permitted to persist. The expression and persistence of macroevolutionary variation in a trait is a manifestation of that trait's versatility. This chapter draws attention to the “third component” of evolvability, which has to do with macroevolutionary production of variation that is ecologically and functionally relevant, and considers how two organismal systems dealt with in this study might illustrate such versatility. The examples treated include in one case a structure—teeth in elephantids—whose morphology is extremely divergent from that in most other mammals and very different from their primitive state. Yet by virtue of their reiterated modular structure and dynamic mode of development, the enormous teeth of elephants have readily adjusted to developing and functioning within jaws of animals whose body sizes have undergone radical change.
Media of Attraction: A Media Archeology Approach to Panoramas, Kinematography, Mixed Reality and Beyond

This paper presents a new concept for understanding contemporary interactive works created with emerging or new media, such as virtual and augmented reality, as part of a larger historically informed category called media of attraction. Inspired by scholarship in film history and media archaeology, the media of attraction concept connects contemporary digital experiments to earlier forms including cabinets of curiosity, 18th century panoramas, pre-filmic moving image technologies, vaudeville, early film or kinematography, and others. Foundational elements defining media of attraction are laid out and discussed. This new approach has profound implications for how work created today is valued and understood, how central debates in the field can be re-contextualized, and how notions of progress can be radically reframed.
‘Pain’ in SNOMED CT: Is There an Anesthetic?

For sure, an unpleasant odor of feet may be categorized as an unpleasant odor. Though foot fetishists (De Block and Adriaens 2013), podiatrists and manufacturers of washing machines might disagree (Question Everything 2015), most people would contend such odor to be classified as an offensive odor. No clinician would have qualms in classifying an unpleasant odor of feet as an odor of feet nor as a foot finding. Perhaps some, in particular the ontology-savvy ones who are therefore able to detect ambiguities in natural language phrases, might doubt a foot odor to be a limb finding or a body odor. But who would argue it to be a finding of sense of smell, i.e. a neurological finding, or a duplicate, and therefore, inactive concept? This question smells of The Systematized Nomenclature of Medicine—Clinical Terms (SNOMED CT) (Donnelly 2006) all over, does it not? Indeed, the former is what its authors argued to be the case until 2003 when they discovered that there are actually two different sorts of smelly feet: “duplicate concept” ones and “offensive body odor” ones. What this discovery means for patients about whom SNOMED CT-based smelly feet assertions were made in their electronic healthcare records (EHR) is rather unclear. Some might, upon chart inspection, be surprised to find their smelly feet to have changed from a neurological finding to an offensive body odor. Others might find their smelly feet to have become inactive concepts and perhaps therefore conclude they are documented as being successfully treated. But in both cases their feet themselves are as stinky as before.
Management of an Immediate Implant Horizontal Defect Using Freeze-Dried Bone Allograft and a Neodymium:Yttrium-Aluminum-Garnet Laser

Introduction: A contemporary protocol for managing horizontal alveolar defects adjacent to immediate implants includes placement of a well-designed provisional restoration to contain graft material and seal the socket. However, immediate provisionalization is not always possible or practical.Case Presentation: A 39-year-old male presented with a non-restorable tooth #29, which was extracted. An immediate implant was placed in the tooth #29 position, and a freeze-dried bone allograft was placed in the horizontal defect between the implant platform and osseous walls. A neodymium:yttrium-aluminum-garnet (Nd:YAG) laser was used to create a stable fibrin clot over the graft material. After 31 months, favorable radiographic bone levels and complete papilla fill were noted.Conclusion: The present case illustrates use of an Nd:YAG laser in the management of an immediate implant horizontal defect in lieu of an immediate provisional restoration.
Synthetic Embryos: Windows into Mammalian Development.

Mammalian embryonic stem cells (ESCs) can self-organize in vitro, but whether they can recreate early embryonic morphogenesis is unclear. Harrison et al. recently demonstrate in Science that 3D co-cultures of mouse ESCs and trophoblast stem cells self-organize into embryo-like structures that recreate many features of early mouse development.
A Service Science Perspective on Entrepreneurship Education

Entrepreneurship and small business education programs have gained popularity globally. Nevertheless, many face difficulty in gaining campus-wide acceptance and sustainability. This paper applies a service science framework, presenting such programs as complex educational service systems that co-produce value for a variety of stakeholders. Access to funding, the presence of enthusiastic champions, trust among stakeholders, coordination and support from constituents are required for entrepreneurship programs to succeed. An implementation of the framework at a technology university is described.
Development and Validation of Trigger Algorithms to Identify Delays in Diagnostic Evaluation of Gastroenterological Cancer.

Background & Aims Colorectal cancer (CRC) and hepatocellular cancer (HCC) are common causes of death and morbidity, and patients benefit from early detection. However, delays in follow-up of suspicious findings are common, and methods to efficiently detect such delays are needed. We developed, refined, and tested trigger algorithms that identify patients with delayed follow-up evaluation of findings suspicious of CRC or HCC. Methods We developed and validated two trigger algorithms that detect delays in diagnostic evaluation of CRC and HCC using laboratory, diagnosis, procedure, and referral codes from the Department of Veteran Affairs National Corporate Data Warehouse. The algorithm initially identified patients with positive test results for iron deficiency anemia or fecal immunochemical test (for CRC) and elevated α-fetoprotein results (for HCC). Our algorithm then excluded patients for whom follow-up evaluation was unnecessary, such as patients with a terminal illness or those who had already completed a follow-up evaluation within 60 days. Clinicians reviewed samples of both delayed and nondelayed records, and review data were used to calculate trigger performance. Results We applied the algorithm for CRC to 245,158 patients seen from January 1, 2013, through December 31, 2013 and identified 1073 patients with delayed follow up. In a review of 400 randomly selected records, we found that our algorithm identified patients with delayed follow-up with a positive predictive value of 56.0% (95% CI, 51.0%–61.0%). We applied the algorithm for HCC to 333,828 patients seen from January 1, 2011 through December 31, 2014, and identified 130 patients with delayed follow-up. During manual review of all 130 records, we found that our algorithm identified patients with delayed follow-up with a positive predictive value of 82.3% (95% CI, 74.4%–88.2%). When we extrapolated the findings to all patients with abnormal results, the algorithm identified patients with delayed follow-up evaluation for CRC with 68.6% sensitivity (95% CI, 65.4%–71.6%) and 81.1% specificity (95% CI, 79.5%–82.6%); it identified patients with delayed follow-up evaluation for HCC with 89.1% sensitivity (95% CI, 81.8%–93.8%) and 96.5% specificity (95% CI, 94.8%–97.7%). Compared to nonselective methods, use of the algorithm reduced the number of records required for review to identify a delay by more than 99%. Conclusions Using data from the Veterans Affairs electronic health record database, we developed an algorithm that greatly reduces the number of record reviews necessary to identify delays in follow-up evaluations for patients with suspected CRC or HCC. This approach offers a more efficient method to identify delayed diagnostic evaluation of gastroenterological cancers.
An improved labeling strategy enables automated detection of single-virus fusion and assessment of HIV-1 protease activity in single virions

Enveloped viruses transfer their genomes into host cells by fusing their membrane to that of the cell. To visualize single-virus fusion in living cells, researchers take advantage of the proteolytic maturation of HIV, type 1 (HIV-1), which can generate free fluorescent proteins within the viral particle. Co-labeling viruses with a content marker and a fluorescently tagged Vpr (a viral core protein) enables detection of single-virus fusions, but a major limitation of this approach is that not all viral particles incorporate both markers. Here we designed a labeling strategy based on the bifunctional mCherry-2xCL-YFP-Vpr construct, in which 2xCL denotes a tandem cleavage site for the viral protease. This bifunctional marker was efficiently cleaved during virus maturation, producing free mCherry and the core-associated YFP-Vpr. A nearly perfect colocalization of these two markers in virions and their fixed 1:1 ratio enabled automated detection of single-particle fusion in both fixed and live cells based on loss of the mCherry signal. Furthermore, a drop in FRET efficiency between YFP and mCherry because of cleavage of the bifunctional marker, which manifested as a marked shift in the normalized YFP/mCherry fluorescence ratio, reliably predicted viral protease activity in single virions. This feature could discriminate between the particles containing free mCherry, and therefore likely representing mature viruses, and immature particles whose fusion cannot be detected. In summary, our new labeling strategy offers several advantages compared with previous approaches, including increased reliability and throughput of detection of viral fusion. We anticipate that our method will have significant utility for studying viral fusion and maturation.
Evaluation of the Relevance of DILI Predictive Hypotheses in Early Drug Development: Review of In Vitro Methodologies vs BDDCS Classification

Drug-induced liver injury (DILI) is a major safety concern; it occurs frequently; it is idiosyncratic; it cannot be adequately predicted; and a multitude of underlying mechanisms has been postulated. A number of experimental approaches to predict human DILI have been proposed utilizing in vitro screening such as inhibition of mitochondrial function, hepatobiliary transporter inhibition, reactive metabolite formation with and without covalent binding, and cellular health, but they have achieved only minimal success. Several studies have shown total administered dose alone or in combination with drug lipophilicity to be correlated with a higher risk of DILI. However, it would be best to have a predictive DILI methodology early in drug development, long before the clinical dose is known. Here we discuss the extent to which Biopharmaceutics Drug Disposition Classification System (BDDCS) defining characteristics, independent of knowing actual drug pharmacokinetics/pharmacodynamics and dose, can be used to evaluate prior published predictive proposals. Our results show that BDDCS Class 2 drugs exhibit the highest DILI severity, and that all of the short-lived published methodologies evaluated here, except when daily dose is known, do not yield markedly better predictions than BDDCS. The assertion that extensively metabolized compounds are at higher risk of developing DILI is confirmed, but can be enhanced by differentiating BDDCS Class 2 from Class 1 drugs. Conclusion: Our published analyses suggest that comparison of proposed DILI prediction methodologies with BDDCS classification is a useful tool to evaluate the potential reliability of newly proposed algorithms, although BDDCS classification itself is not sufficiently predictive. Almost all of the predictive DILI metrics do no better than just avoiding BDDCS Class 2 drugs, although some early data with microliver platforms enabling long-enduring metabolic competency show promising results.