cssi/SciSciGPT-SciSciNet huggingface dataset:
Universal Reinforcement Learning

We consider an agent interacting with an unmodeled environment. At each time, the agent makes an observation, takes an action, and incurs a cost. Its actions can influence future observations and costs. The goal is to minimize the long-term average cost. We propose a novel algorithm, known as the active LZ algorithm, for optimal control based on ideas from the Lempel-Ziv scheme for universal data compression and prediction. We establish that, under the active LZ algorithm, if there exists an integer K such that the future is conditionally independent of the past given a window of K consecutive actions and observations, then the average cost converges to the optimum. Experimental results involving the game of Rock-Paper-Scissors illustrate merits of the algorithm.
Exploring chaos automata for protein sequences

Fractals have been used to visually represent biological sequences since 1990. At first simple chaos games were used to generate fractal visualizations for DNA sequences, but the technique developed into using more complex systems to visually represent DNA and protein sequences. One of these more complex systems, termed chaos automata, combined iterated function systems with finite state automata to retain a memory of sequence input. The parameters for chaos automata were evolved by evolutionary algorithm to distinguish between different properties in DNA sequence input. Here, chaos automata have been extended to protein sequences and explored using synthetic protein sequence data.
Changing atmospheric carbon dioxide: A threat or benefit?

Abstract Atmospheric carbon dioxide (CO 2 ) concentrations are rapidly increasing, having risen by about 100 ppm over the last century. Atmospheric CO 2 is the basic photosynthetic building block of plants and is respired to generate the plant's energy. Atmospheric CO 2 in enhanced conditions is like an “all-you-can-eat buffet” for trees. But are there hidden threats from rising atmospheric CO 2 ? Are the world's forests sinks or sources of CO 2 ? What will they be in the future? Can we slow the rise in atmospheric CO 2 with more intensive forestry efforts? How effective can intensive forestry practices be in sequestering carbon? Simultaneous with increasing CO 2 , other greenhouse gases such as NO x and O 3 are also rapidly increasing in the atmosphere. Will these gases be beneficial or detrimental to trees under elevated CO 2 ? This chapter will address these questions and will use our current understanding of forest function to gain insight into how future forests will be affected by increasing greenhouse gases. Finally, we address the potential of afforestation, reforestation, agroforestry and forest management for increasing carbon sequestration.
Pharmaceuticals: Access, Cost, Pricing, and Directions for the Future

Prescription drug expenditures make up less than 10 percent of total personal health care expenditures in the United States, but over the last decade the amount that Americans spend on prescription drugs has grown much faster than any other component of personal health care. For example, between 1999 and 2000, hospital care costs rose about 5 percent, physicians and clinical services 6 percent, while prescription drug expenditures climbed more than 17 percent. In dollar amounts, prescription drug expenditures doubled, from $61 billion to $122 billion, between 1995 and 2000. Is this an unwarranted expense that needs to be controlled, or does it represent increased value, as pharmaceuticals substitute for older, most costly treatments? What is the prevalence of health insurance coverage for prescription drugs, and how does this affect specific populations who have limited or no drug benefits? What are the components of drug prices? And what do we need to consider when we design health care policy? Stephen Soumerai and Patricia Danzon look at several aspects of pharmaceutical drug usage and pricing in the United States, illustrating their observations with their published research findings. They then briefly review recent legislative proposals to broaden public insurance coverage for prescription drugs and make their own policy recommendations.
Activation of signaling pathways downstream of the brain-derived neurotrophic factor receptor, TrkB, in the rat brain by vagal nerve stimulation and antidepressant drugs

Vagal nerve stimulation (VNS) has been approved for treatment resistant depression (TRD) by the Food and Drug Administration (FDA) since 2005. However, the cellular and molecular targets responsible for its effects are still not characterized. Previously, chronic administration of VNS to rats was found to phosphorylate tyrosine 515 on TrkB, the neurotrophin receptor, whereas traditional antidepressants did not do this. In the present study, Western blot analysis was used to characterize activation due to phosphorylation in the hippocampus of downstream pathways linked to specific key tyrosine residues on TrkB (namely Y816 and Y515) after either acute or chronic administration of VNS and traditional antidepressant drugs. Chronic administration of VNS caused phosphorylation of effectors linked to Y 515; namely Akt, ERK and p70S6 kinase, but this was not produced by either desipramine or sertraline. All the treatments, when given chronically, caused phosphorylation of the transcription factor, CREB. Acute administration of all the treatments also caused phosphorylation of PLCγ1 but this was not maintained with chronic treatment. Further research is required to determine what role, if any, activation of down-stream targets of Y515 plays in the behavioural effects of VNS. Received 27 April 2013; Reviewed 3 June 2013; Revised 23 July 2013; Accepted 25 July 2013; First published online 8 October 2013
Influence of concomitant prednisolone on trimethoprim-associated hyperkalaemia

Objectives: Trimethoprim–sulfamethoxazole may cause hyperkalaemia by the amiloride-like effect of trimethoprim on sodium channels in the distal nephron. Hyperkalaemia usually occurs after 7–10 days and has been reported in 20%–50% of patients receiving trimethoprim–sulfamethoxazole. Patients with Pneumocystis jiroveci pneumonia and severe hypoxaemia benefit from the use of prednisolone as an adjuvant to trimethoprim–sulfamethoxazole. The addition of prednisolone may lower the incidence of trimethoprim-related hyperkalaemia due, in part, to its mineralocorticoid activity. We studied the effect of concomitant prednisolone on trimethoprim-related hyperkalaemia. Patients: Thirty patients qualified for inclusion and were reviewed. Patients were divided into two groups: one group received trimethoprim–sulfamethoxazole plus prednisolone (18 patients); and the other group received trimethoprim–sulfamethoxazole alone (12 patients). Results: The two groups were comparable at baseline, except for the severity of the P. jiroveci pneumonia. Hyperkalaemia developed in seven patients: all in the prednisolone and trimethoprim–sulfamethoxazole group. The greater incidence of hyperkalaemia in this group is surprising and was counter to our expectation. Conclusions: Although it is possible that there is an unexplained interaction between trimethoprim and prednisolone, we postulate that our observation is a result of the catabolic effect of prednisolone. The patients treated with trimethoprim–sulfamethoxazole plus prednisolone appear to be more likely to develop hyperkalaemia than patients treated with trimethoprim–sulfamethoxazole alone.
Convergent-Discriminant Validity of the Jewish Employment and Vocational Service System

This study investigated the construct validity of five perceptual traits with five simulated work samples from the Jewish Employment and Vocational Service Work Sample System (JEVS). The subjects, mean CA 14.4, were thirty-six applicants with learning disabilities who attended a prevocational assessment program. Utilizing the paradigm of convergent-discriminant validity, convergent validity (p < .01) was evidenced in four of the five work samples and discriminant validity (p < .01) was demonstrated in three of the five work samples. The results indicate that simulated work samples can be used as a diagnostic instrument for assessment of perceptual abilities in a vocational setting.
An all hops optimal algorithm for dynamic routing of sliding scheduled traffic demands

We consider dynamic routing of holding-time aware demands under a sliding scheduled traffic model to satisfy demands' bandwidth and timing requirements. We propose an all hops optimal routing algorithm that iteratively finds all feasible paths of at most h hops at the end of h-th iteration. We prove the correctness and analyze the time complexity of the algorithm.
Digitally adjusting chromogenic dye proportions in brightfield microscopy images

We present an algorithm to adjust the contrast of individual dyes from colour (red-green-blue) images of dye mixtures. Our technique is based on first decomposing the colour image into individual dye components, then adjusting each of the dye components and finally mixing the individual dyes to generate colour images. Specifically in this paper, we digitally adjust the staining proportions of hematoxylin and eosin (H&E) chromogenic dyes in tissue images. We formulate the physical dye absorption process as a non-negative mixing equation, and solve the individual components using non-negative matrix factorisation (NMF). Our NMF formulation includes camera dark current in addition to the mixing proportions and the individual H and E components. The novelty of our approach is to adjust the dye proportions while preserving the color of nonlinear dye interactions, such as pigments and red blood cells. In this paper we present results for only H&E images, our technique can easily be extended to other staining techniques.
Cytochrome P450 Arachidonic Acid ω‐Hydroxylation in the Proximal Tubule of the Rat Kidneya

20-Hydroxy-5,8,11,14-eicosatetraenoic acid (20-HETE) is a major cytochrome P450-dependent arachidonate metabolite in the rat kidney. In the present study we characterized the formation of 20-HETE in the proximal tubule, the nephron segment with the highest concentration of cytochrome P450 activities, including P450 arachidonic acid metabolism. Freshly isolated tubules showed a basal formation of 20-HETE, implying that it is an endogenous constituent of the proximal tubule. Conversion of exogenous arachidonic acid to 20-HETE in proximal tubule homogenates was enzymatic and NADPH-dependent (i.e., 0 and 65.5 +/- 1.1 pmol/mg/min in the absence and presence of NADPH, respectively). That its formation was not affected by indomethacin but inhibited following preincubation with 17-ODYA (17-octadecynoic acid) and 7-ER (7-ethoxyresorufin) suggested that a P450 monooxygenase activity was involved in its synthesis. This was further strengthened by the demonstration that antibody raised against the rat cytochrome P450 4A1, a major fatty acid omega-hydroxylase isozyme, inhibited 20-HETE formation, suggesting the involvement of a P450 4A1 or P450 4A1-like activity in this reaction. Pretreatment of rats with clofibrate and dexamethasone, inducers of the P450 4A gene family, yielded a twofold increase in the proximal tubular synthesis of 20-HETE as well as an increase in P450 4A1 mRNA. These results, together with previous demonstrations that 20-HETE vasoconstricts isolated blood vessels, namely, renal microvessels, and affects tubular ion transport, suggest a role for 20-HETE in the regulation of renal vascular tone and transport functions and further stress the importance of understanding the regulation of 20-HETE synthesis in the kidney.
Three‐Way Interactions among Mutualistic Mycorrhizal Fungi, Plants, and Plant Enemies: Hypotheses and Synthesis

Abstract: A number of studies have shown that an association with mycorrhizal fungi can alter the outcome of interactions between plants and their enemies. While the directions of these effects vary, their strength suggests the need for greater attention to multispecies interactions among plant enemies, plants, and mycorrhizal fungi. We recognize that mycorrhizal fungi could effect plant enemies by improving plant nutrition, modifying plant tolerance, or modifying plant defenses. In addition, mycorrhizal fungi could directly interfere with pathogen infection, herbivory, or parasitism by occupying root space. We formalize these alternative outcomes of multispecies interactions and explore the long‐term dynamics of the plant‐enemy interactions based on these different scenarios using a general model of interactions between plants and plant enemies. We then review the literature in terms of the assumptions of the alternative mechanisms and the predictions of these models. Through this effort, we identify new...
Plane-Strain Plastic Wave Propagation in a Dynamically Loaded Hollow Cylinder

An experimental technique to create plane-strain plastic stress waves, propagating radially from the center of a hollow cylindrical specimen, is described. An optical system is used to measure the circumferential strain variation as a function of time, the propagation velocities, and, indirectly, the pressure loading required to produce these strains. A comparison is made between the experimental results and the theoretical predictions of a rate-independent plasticity theory for an aluminum alloy.
Shifting the Center of Economic Gravity Towards Innovation in Asia -- A Comprehensive Review of Leapfrogging Asian Business Innovators in China, India, Japan, Singapore, and South Korea

This research notes that the ascendancy of Asia’s economic growth coincides with the exigencies of shifting center of economic gravity towards innovation, while the two other pillars of economic growth, the quantity of labor force and capital formation, become increasingly subdued in growth potential.The research study takes a case-specific approach to investigate into the leapfrogging innovations, providing a distinctive perspective to understand Asian business innovation, distinguishing itself from both the traditional corporate surveys and index-based or empirical approaches. By contrast, this research navigates through forefront innovation leaders in real scenarios, and also presents a panorama, with a combination of storytelling and pattern analysis.The research, understanding innovations with the special relevance of market, regulatory, societal, and cultural contexts, serves its primary end to inform businesses in Asia and by Asia. This study also sheds light upon innovations elsewhere, especially Europe and North America businesses — the other two leading hubs of business innovators.
Parent-Reported Errors and Adverse Events in Hospitalized Children.

Importance Limited data exist regarding the incidence and nature of patient- and family-reported medical errors, particularly in pediatrics. Objective To determine the frequency with which parents experience patient safety incidents and the proportion of reported incidents that meet standard definitions of medical errors and preventable adverse events (AEs). Design, Setting, and Participants We conducted a prospective cohort study from May 2013 to October 2014 within 2 general pediatric units at a children’s hospital. Included in the study were English-speaking parents (N = 471) of randomly selected inpatients (ages 0-17 years) prior to discharge. Parents reported via written survey whether their child experienced any safety incidents during hospitalization. Two physician reviewers classified incidents as medical errors, other quality issues, or exclusions (κ = 0.64; agreement = 78%). They then categorized medical errors as harmful (ie, preventable AEs) or nonharmful (κ = 0.77; agreement = 89%). We analyzed errors/AEs using descriptive statistics and explored predictors of parent-reported errors using bivariate statistics. We subsequently reviewed patient medical records to determine the number of parent-reported errors that were present in the medical record. We obtained demographic/clinical data from hospital administrative records. Main Outcomes and Measures Medical errors and preventable AEs. Results The mean (SD) age of the 383 parents surveyed was 36.6 (8.9) years; most respondents (n = 266) were female. Of 383 parents surveyed (81% response rate), 34 parents (8.9%) reported 37 safety incidents. Among these, 62% (n = 23, 6.0 per 100 admissions) were determined to be medical errors on physician review, 24% (n = 9) were determined to be other quality problems, and 14% (n = 5) were determined to be neither. Thirty percent (n = 7, 1.8 per 100 admissions) of medical errors caused harm (ie, were preventable AEs). On bivariate analysis, children with medical errors appeared to have longer lengths of stay (median [interquartile range], 2.9 days [2.2-6.9] vs 2.5 days [1.9-4.1]; P = .04), more often had a metabolic (14.3% vs 3.0%; P = .04) or neuromuscular (14.3% vs 3.6%; P = .05) condition, and more often had an annual household income greater than $100 000 (38.1% vs 30.1%; P = .06) than those without errors. Fifty-seven percent (n = 13) of parent-reported medical errors were also identified on subsequent medical record review. Conclusions and Relevance Parents frequently reported errors and preventable AEs, many of which were not otherwise documented in the medical record. Families are an underused source of data about errors, particularly preventable AEs. Hospitals may wish to consider incorporating family reports into routine safety surveillance systems.
Variations in Megastigmus from Rose Hips (Torymidae, Hymenoptera)

The two known species of Megastigmus from rose hips afford an unusually favorable group for a study of intraspecific and interspecific variation in size and color of the adults. They are very closely related (Milliron, 1949, p. 293), and have very similar habits and development, yet show striking differences as to the range of variation in size and color and also the numerical ratios of the sexes. The American form, Megastigmus nigrovariegatus Ashmead, and particularly the male, varies extremely in the percents of dark color, i.e., brown to black versus yellow pigmented areas on the body, and apparently comprises equal numbers of males and females. By contrast, the European species, M. aculeatus (Swederus), now known to occur also in Japan, China and the United States of America, shows, in my reared series, comparatively little range in color and size, and is predominantly female.
Irradiation Disinfestation of Cornmeal

Naturally or artificially infested white or yellow cornmeal was packed in metal cans (14.5 kg/can) and irradiated with absorbed doses of gamma irradiation from 15.8–62.5 krad. Doses of 35.5 krad or less were inadequate to control populations of mixed stages of the Indian meal moth, Plodia interpunctella (Hubner), the red flour beetle, Tribolium castaneum (Herbst), and the lesser grain borer, Rhyzopertha dominica (F.), within 1 month, but a dose of 15.8 krad or above resulted in 100% mortality of all stages of all species present in the cornmeal within 3 months of irradiation. The results showed that, if mortality of all eggs and young larvae of all species is to be complete by the end of 1 month, the selected dose must be near the upper limit permitted by current U.S. Food and Drug Administration regulations (50 krad); but if delayed mortality is acceptable, the lowest approved dose (20 krad) is adequate.
Improved Solution of Nonlinear Reduced-Order Models for Static and Dynamic Response Prediction

Nonlinear reduced-order models (NLROMs) have been used recently to predict the response of stiffened shell structures subjected to extreme acoustic loading and aerodynamic heating. The NLROMs are essentially modal models augmented with nonlinear terms to capture the large amplitude, nonlinear geometric effects. Temperature dependent linear stiffness terms can be added to capture thermal effects. Numerical stability issues have risen for quasi-static and dynamic simulations using the NLROMs. Most of these issues have been solved through the use of very high sample rates. However, these stability issues are more severe with thermal models of curved structures with softening effects. In this paper, the nonlinear terms of the reduced-order models will be re-cast in an alternate form that allows for more robust solution techniques. An example problem with a curved panel subjected to a thermal loading shows the benefits of the improved solution procedures.
Dynamics of nearly spherical bubbles in a turbulent channel upflow

The dynamics of bubbles in upflow, in a vertical channel, is examined using direct numerical simulations (DNS), where both the flow and the bubbles are fully resolved. Two cases are simulated. In one case all the bubbles are of the same size and sufficiently small so they remain nearly spherical. In the second case, some of the small bubbles are coalesced into one large bubble. In both cases lift forces drive small bubbles to the wall, removing bubbles from the channel interior until the two-phase mixture is in hydrostatic equilibrium, and forming a bubble-rich wall layer. The same evolution has been seen in earlier DNS of bubbly upflows, but here the friction Reynolds number is higher ( ). In addition to showing that the overall structure persists at higher Reynolds numbers, we show that the bubbles in the wall layer form clusters. The mechanism responsible for the clustering is explained and how bubbles move into and out of the wall layer is examined. The dynamics of the bubbles in the channel core is also compared with results obtained in fully periodic domains and found to be similar. The presence of the large bubble disrupts the wall layer slightly, but does not change the overall picture much, for the parameters examined here.
Actue kidney injury of mice induced by Agkistrodon halys pallas venom

Objective To observe the changes of pathology in kidney and to provide a theoretical basis for prevention and treatment of renal injury induced by Agkistrodon halys Pallas venom.Methods Three groups were designed in this experiment:group N(normal control group),group L(low-dose group,0.50 mg/kg) and group H(high-dose group,2.00 mg/kg) according to the dose of Agkistrodon halys Pallas venom.All were further divided into four sub groups at 3 h,6 h,24 h and 48 h.A total of 96 Kunming mice were randomly equally assigned to each sub-group and each mouse was injected intramuscularly.Results The level of SCr were observed among group N,L and H.It elevated at 24 h and decreased by 48 h in group L,while continues to rise in group H.The pathology score of kidney tissue were still observed.It elevated at 24 h and decreased by 48 h in group L,while continues to rise in group H.The level of SCr was positively correlated with the pathology score of kidney tissue(L:r=0.883,P0.01;H:r=0.891,P0.01).Conclusion SCr can reflect the severity of renal injury under certain conditions,but the incidence of acute kidney injury is earlier than the elevation of SCr.The severity of actue kidney injury is related to the dose of venom.
Advances in endometrial pathology.

This article updates the classification and grading of endometrial carcinoma. Criteria for distinguishing types of endometrial tumors are provided. The current understanding of the pathogenesis of carcinosarcoma is reviewed. The literature on two recently described entities, adenosarcoma and atypical polypoid adenomyoma, is summarized.
Burns in the Geriatric Population

The population is aging, so the number of elderly burn patients continues to rise. There are differences in the skin and the physiology of the elderly that a burn caregiver must know. The geriatric population tends to be less able to handle the same size burn as those who are younger, but their outcomes continue to improve. This chapter reviews the differences between the younger population and the elderly.
Radial Tilting of the Extracellular Domain of GLIC Revealed by EPR Spectroscopy

Signaling in the brain depends on rapid opening and closing of pentameric ligand-gated ion channels (pLGICs). Defects in these proteins are linked to a variety of diseases including myasthenia, epilepsy and sleep-disorders. In addition, these proteins are therapeutic targets for various drugs including anti-convulsants, anxiolytics, anesthetics and sedatives. While recent crystal structures of prokaryotic and eukaryotic pLGICs solved in detergent micelles have shed light on the molecular architecture of these proteins, describing their conformational dynamics in physiological lipids is essential for understanding their function. Crystal structures of GLIC and the glutamate-activated chloride channel predict that agonist-mediated channel opening is associated with a quaternary twisting and a radial un-blooming (inward tilting) of the extracellular binding domain (ECD). Using site directed spin labeling electron paramagnetic resonance (SDSL EPR) spectroscopy and functional GLIC channels reconstituted in liposomes, we are testing these gating predictions. Residues located at the top of β-strands (β1, 2, 5, 6, 8) were mutated to cysteine, labeled with the spin probe MTSL and proton-induced gating motions were measured using continuous wave (CW) and double electron-electron resonance (DEER) spectroscopy. CW EPR spectroscopy data showed the spin label attached to I92C, S93C, V94C (β5), T99C and Q101C (β6) moved into a slightly more constrained/immobile environment at pH 3.0 as compared to pH 7.6. DEER distance distributions for K48 (β2), S93 (β5), T99 and Q101 (β6) revealed the probes moved closer together at pH 3.0, suggesting that the inner β-sheet of the extracellular domain of GLIC tilt inwards upon agonist activation.
Elemental Abundances in the Solar Upper Atmosphere Derived by Spectroscopic Means

The composition of the solar photosphere is believed to be uniform. Indeed a quantity that does not vary with solar surface location or with a particular solar feature, i.e., no observational evidence is available to indicate that the photospheric composition near the solar equator is different from the photospheric composition near the solar poles or that the photospheric composition in quiet regions is different from the composition in active regions. In contrast, the composition of the solar upper atmosphere is not well defined. Solar composition work in recent decades has brought the recognition that there are systematic differences between the composition of the corona and the photosphere and revealed evidence for spatial and time variability in the composition of various coronal features. We review the spectroscopic techniques used and the progress that was made in recent years in deriving the plasma compositions of various solar upper atmosphere structures.
Sparse-coded net model and applications

As an unsupervised learning method, sparse coding can discover high-level representations for an input in a large variety of learning problems. Under semi-supervised settings, sparse coding is used to extract features for a supervised task such as classification. While sparse representations learned from unlabeled data independently of the supervised task perform well, we argue that sparse coding should also be built as a holistic learning unit optimizing on the supervised task objectives more explicitly. In this paper, we propose sparse-coded net, a feedforward model that integrates sparse coding and task-driven output layers, and describe training methods in detail. After pretraining a sparse-coded net via semi-supervised learning, we optimize its task-specific performance in a novel backpropagation algorithm that can traverse nonlinear feature pooling operators to update the dictionary. Thus, sparse-coded net can be applied to supervised dictionary learning. We evaluate sparse-coded net with classification problems in sound, image, and text data. The results confirm a significant improvement over semi-supervised learning as well as superior classification performance against deep stacked autoencoder neural network and GMM-SVM pipelines in small to medium-scale settings.
Jazz Tap Originals: A Collection of Live Performances (1979–2012)

Two men dressed in blue coveralls, their faces semi-obscured by the big hairdos, beards, and large-frame glasses typical of 1983 fashion, syncopate each other’s footsteps with successive accents th...
A polynomial rooting based ML CFO estimator in multipath channel with repetitive pilot symbols

In this paper, we introduce a polynomial rooting based method for data-aided carrier frequency offset (CFO) estimation in the presence of frequency selective multipath fading. This estimator follows the maximum-likelihood (ML) criterion and offers a reduction in computational complexity when the pilot symbols are repetitive. Our analysis shows that depending on the number of repetitions and the length of each repetition, polynomial rooting based ML CFO estimator could be more numerically robust than search based ML CFO estimator. It is also observed that the polynomial rooting based CFO estimator achieves the Cramer-Rao bound at moderately low signal-to-noise ratio.
Targeted Therapy for Localized Kidney Cancer

Due to the widespread use of abdominal imaging, the number of incidentally detected renal cortical neoplasms has significantly increased. There are multiple treatment modalities in the management of renal masses, including active surveillance for indolent and slow-growing tumors and extirpation, which remains the gold standard treatment. Thermal ablation, which in contemporary practice is currently largely defined as including cryoablation and radiofrequency ablation, has emerged as an alternative treatment option in selected patients with a small renal cortical neoplasm. With the continuous improvements in contemporary imaging modalities such as computer tomography, magnetic resonance imaging, and facilitated ultrasound technology, the role of ablation in the management of renal cortical neoplasms will almost certainly expand. Additionally, the truly minimally invasive nature of percutaneous image-guided ablation will further increase the appeal of ablative technologies. Emerging long-term follow-up data after cryoablation and radiofrequency ablation is promising with 5- and 10-year cancer-specific survival rates approaching extirpation treatment modalities. Repeat ablation after primary failure of cryoablation is feasible and safe with excellent medium-term follow-up outcomes. In this chapter, we will discuss the current state of thermal ablation including cryoablation and radiofrequency ablation. We will provide details on indications for thermal ablation and patient selection, surgical techniques, and perioperative outcomes. Finally, we will summarize the long-term oncologic outcomes of thermal ablation and the results of salvage cryoablation.
Abstract 104: Protein Kinase GIα Functions in the Cardiac Myocyte as a Tonic Inhibitor of Pathologic Cardiac Hypertrophy In Vivo

Objectives: We and others previously demonstrated that activation of the NO-cGMP-Protein Kinase G (PKG) pathway inhibits cardiac hypertrophy and remodeling in vivo. However, it remains untested whether PKG specifically in the cardiac myocyte (CM) mediates these effects. We therefore tested the hypothesis that PKGIα inhibits pathologic cardiac hypertrophy through a specific role in the CM. Methods and Results: We created and characterized mice with CM-restricted excision of PKGIα. Mice were generated in which the PKGI exon 1 (specific for the Iα isoform) was flanked by loxP sites. We crossed these PKGIα fl/fl mice with αMHC-Cre mice which constitutively express Cre recombinase selectively in the CM. The resultant PKGIα fl/fl / αMHC-Cre+/- mice were compared with PKGIα fl/fl / αMHC-Cre-/- littermate controls (termed PKG CMKO and Ctrl, respectively). By age 3 months (n=5 per genotype), male PKG CMKO mice developed atrial and LV hypertrophy compared with Ctrl littermates PKG CMKO atrial weight/tibia length 0.33 ± 0.03 mg/mm vs 0.22 ± .01 in Ctrl, P CMKO LV/TL 5.0 ± 0.2 mg/mm vs 4.1 ± 0.4 in Ctrl, P CMKO mice (9445 ± 282 pixels PKG CMKO vs 8273 ± 213 in Ctrl, n>400 cells/genotype, 5 hearts per genotype; P CMKO mice (PKG CMKO 3.1 ± 0.4 mmHg/μ l vs 6.1 ± 1.0 in Ctrl-; P CMKO mice developed early mortality (3 of 4 PKG CMKO males died at 6 months of age vs 0 of 4 Ctrl males). Total heart and atrial weights of male mice (n=3 PKG CMKO , 4 Ctrl) increased in PKG CMKO mice (heart weight/tibia length 10.8 ± 1.7 mg/mm in PKG CMKO vs 7.1 ± 0.6 in Ctrl; P CMKO vs 0.30 ± 0.1 Ctrl, P CMKO mice as well (35 ± 3% PKG CMKO vs 44 ± 4% Ctrl, P 0.09). Conclusions: These data provide the first evidence that PKGIα functions in the CM as a tonic inhibitor of age-dependent pathologic hypertrophy, supporting further study of PKGIα as a therapeutic target in the prevention and treatment of LV remodeling and congestive heart failure.
Complete surgical resection improves outcome in INRG high-risk patients with localized neuroblastoma older than 18 months

Although several studies have been conducted on the role of surgery in localized neuroblastoma, the impact of surgical timing and extent of primary tumor resection on outcome in high-risk patients remains controversial. Patients from the German neuroblastoma trial NB97 with localized neuroblastoma INSS stage 1–3 age > 18 months were included for retrospective analysis. Imaging reports were reviewed by two independent physicians for Image Defined Risk Factors (IDRF). Operation notes and corresponding imaging reports were analyzed for surgical radicality. The extent of tumor resection was classified as complete resection (95–100%), gross total resection (90–95%), incomplete resection (50–90%), and biopsy (<50%) and correlated with local control rate and outcome. Patients were stratified according to the International Neuroblastoma Risk Group (INRG) staging system. Survival curves were estimated according to the method of Kaplan and Meier and compared by the log-rank test. A total of 179 patients were included in this study. 77 patients underwent more than one primary tumor operation. After best surgery, 68.7% of patients achieved complete resection of the primary tumor, 16.8% gross total resection, 14.0% incomplete surgery, and 0.5% biopsy only. The cumulative complication rate was 20.3% and the surgery associated mortality rate was 1.1%. Image defined risk factors (IDRF) predicted the extent of resection. Patients with complete resection had a better local-progression-free survival (LPFS), event-free survival (EFS) and OS (overall survival) than the other groups. Subgroup analyses showed better EFS, LPFS and OS for patients with complete resection in INRG high-risk patients. Multivariable analyses revealed resection (complete vs. other), and MYCN (non-amplified vs. amplified) as independent prognostic factors for EFS, LPFS and OS. In patients with localized neuroblastoma age 18 months or older, especially in INRG high-risk patients harboring MYCN amplification, extended surgery of the primary tumor site improved local control rate and survival with an acceptable risk of complications.
Matrices over PIDs

Recall that if T i : V→V (i = 1,2) are linear transformations on a finite-dimensional vector space V over a field F, then T1 and T2 are similar if and only if the F[X]-modules VT1 and VT2 are isomorphic (Theorem 4.4.2). Since the structure theorem for finitely generated torsion F[X]-modules gives a criterion for isomorphism in terms of the invariant factors (or elementary divisors), one has a powerful tool for studying linear transformations, up to similarity. Unfortunately, in general it is difficult to obtain the invariant factors or elementary divisors of a given linear transformation. We will approach the problem of computation of invariant factors in this chapter by studying a specific presentation of the F[X]-module VT. This presentation will be used to transform the search for invariant factors into performing elementary row and column operations on a matrix with polynomial entries. We begin with the following definition.
Importance of an alternative approach to measuring quality in a volume-to-value world: a case study of diabetes care

Background To develop a statistical tool that allows practitioners and/or their practice managers to easily select the relevant range in which volume and value are maximised. Methods Data for the study were based on 55 primary care practices that participated in the Colorado Improving Performance in Practice programme in 2014. We used two composite variables including the volume of processes of care variables listed in Diabetes Practice Guidelines and value (quality) as measured by changes in the intermediate outcomes. We assessed volume/value trade-offs using a multilevel model with a time-varying covariate partitioned into a between-practice and within-practice effect. Results The study revealed a strong linear relationship between volume and value (P Conclusion Such findings suggest an inherent linkage between volume of care and quality. This statistical approach, if provided as an app containing an easy-to-use statistical calculator, will allow practice managers and clinicians to systematically identify volume/quality trade-offs, thereby reducing undertreatment and/or overtreatment among patients with chronicities.
Click-Addressable Cassette for Photoaffinity Labeling.

A small molecule 1 was designed to contain an alkyne, a trifluoromethyl phenyldiazirine, and a free piperidine-NH for facile conjugation to protein binding ligands. This “cassette” 1 was synthesized via a relatively direct route involving only routine steps. In this proof-of-concept study, putative ligands for carbonic anhydrase IX and for TrkC were conjugated to 1. Photoaffinity labeling was performed using purified extracellular regions of both these protein-receptors, and using cells that express these receptors (isolation via a pull-down procedure), labeling of the protein was observed in all four experiments.
Assisting Students with Intellectual and Developmental Disabilities in Inclusive Education with Smartwatches

Smartwatches have a large potential to support everyday activities. However, their potential as assistive technologies in inclusive academic environments is unclear. To investigate how smartwatches can support students with intellectual and developmental disabilities (IDDs) to perform activities that require emotional and behavioral skills and involve communication, collaboration and planning, we implemented WELI. WELI (Wearable Life) is a wearable application designed to assist young adults with IDDs attending a postsecondary education program. This paper reports on the user-centric design process adopted in the development of WELI, and describes how smartwatches can assist students with IDDs in special education. The results reported are drawn from 8 user studies with 58 participants in total. WELI features include behavioral intervention, mood regulation, reminders, checklists, surveys and rewards. Results indicate that several considerations must be taken into account when designing for students with IDD, and that overall the students are enthusiastic about adopting an innovative smartwatch application in class, as they reacted positively about the technology and features provided.
Spontaneous nanostructure formation in GaAsBi alloys

Abstract Bismuth containing semiconductor alloys are of increasing interest for their potential applications as infrared devices, though material quality in these materials has often proven problematic. This work shows a series of GaAsBi films grown by molecular beam epitaxy over a range of temperatures, 340 °C–315 °C, with all other parameters equal. Atomic force microscopy shows that there is an increase in the surface roughness of the films from 0.8 nm to 2.7 nm RMS. Transmission electron microscopy and atom probe tomography reveals the onset of spontaneous nanostructure formation in the films including nanopores, lateral composition modulation, and Bi rich GaAsBi clusters. The phenomena are shown to correlate and linked to reaching a growth instability due to the differences in surface diffusivity of Bi and As adatoms.
Predictors and outcomes of perioperative blood transfusions in classic bladder exstrophy repair: A single institution study

Summary Background Primary bladder closure of classic bladder exstrophy (CBE) is a major operation that occasionally requires intraoperative or postoperative (within 72 h) blood transfusions. Objective This study reported perioperative transfusion rates, risk factors for transfusion, and outcomes from a high-volume exstrophy center in primary bladder closure of CBE patients. Study design A prospectively maintained, institutional exstrophy–epispadias complex database of 1305 patients was reviewed for primary CBE closures performed at the authors' institution (Johns Hopkins Hospital) between 1993 and 2017. Patient and surgical factors were analyzed to determine transfusion rates, risk factors for transfusions, and outcomes. Patients were subdivided into two groups based upon the time of closure: neonatal and delayed closure. Results A total of 116 patients had a primary bladder closure during 1993–2017. Seventy-three patients were closed in the neonatal period, and 43 were delayed closures. In total, 64 (55%) patients received perioperative transfusions. No transfusion reactions were observed. Twenty-five transfusions were in the neonatal closure group, yielding a transfusion rate of 34%. In comparison, 39 patients were transfused in the delayed closure group, giving a transfusion rate of 91%. Pelvic osteotomy, delayed bladder closure, higher estimated blood loss (EBL), larger pubic diastasis, and longer operative time were all associated with blood transfusion. In multivariable logistic regression, pelvic osteotomy (OR 5.4; 95% CI 1.3–22.8; P Discussion This was the first study from a single high-volume exstrophy center to explore factors that contribute to perioperative blood transfusions. Pelvic osteotomy as a risk factor was unsurprising, as the osteotomy may bleed both during and immediately after closure. However, it is important to use osteotomy for successful closure, despite the increased transfusion risk. The risks accompanying contemporary transfusions are minimal and osteotomies are imperative for successful bladder closure. Conclusions More than half of CBE patients undergoing primary closure at a single institution received perioperative blood transfusions. While there was an association between transfusions and osteotomy, delayed primary closure, larger diastasis, increased operative time, and increased length of stay, only the use of pelvic osteotomy, higher EBL-to-weight ratio, and recent year of closure independently increased the odds of receiving a transfusion on multivariate analysis. Summary Table . Logistic regression to determine factors that are associated with receiving a perioperative blood transfusion in patients undergoing repair of classic bladder exstrophy. Covariate Univariate Multivariate OR 95% [CI] P-value OR 95% [CI] P-value Osteotomy 14.6 [5.9–36.0] 5.4 [1.3–22.8] 0.021 EBL-weight ratio 1.10 [1.06–1.16] 1.01 [1.003–1.13] 0.001 Year of closure 1.1 [1.03–1.17] 0.03 1.1 [1.0–1.2] 0.018 Hb, hemoglobin; ASA, American Society of Anesthesiologists; EBL, estimated blood loss.
Treatment Refractory Ocular Symptoms in Myasthenia Gravis: Clinical and Therapeutic Profile (P6.445)

Objective: To review clinical characteristics of patients with treatment resistant ocular symptoms in myasthenia gravis (MG). Background: Most MG patients (85%) develop ocular symptoms over the course of the disease. Despite many therapeutic options available for management of MG, some patients remain resistant to standard therapies. Design/Methods: We performed a retrospective chart review of MG patients with treatment resistant ocular symptoms. Treatment resistance was defined as persistent diplopia or ptosis despite prednisone and at least one additional immunosuppressive agent. After IRB approval, patient’s charts were reviewed to abstract demographic, clinical, diagnostic and therapeutic information. Results: We identified 4 patients with acetylcholine receptor antibody positive MG with treatment resistant ocular symptoms attending our clinics. The median age of MG onset was 26 years (range of 23 to 61). Three patients had ocular symptoms at onset and developed generalized MG at some time along the course of their illness. The fourth case continued to have ocular MG. High dose steroid was started immediately after the symptom onset in 2/4 patients, 3 months after onset in one patient and 8 years after onset in one patient. The median time interval between the onset of MG to the refractory ocular symptoms was 13 years (range of 3 to 25). Initial partial response was reported with pyridostigmine in 3/4 patients, high dose steroids in 2/4 patients, other immunosuppressive agents in 1/3 patients, IVIG in 2/3 patients. None of the 3 patients who had plasmapheresis (PLEX) showed any significant improvement. Ocular symptoms persisted in all 4 patients despite all therapies. Conclusions: MG patients with treatment refractory ocular symptoms are mostly younger at disease onset and had earlier ocular symptoms. Ocular symptoms were resistant to PLEX and IVIG. Disclosure: Dr. Sharma has nothing to disclose. Dr Pasnoor has nothing to disclose. Dr. Dimachkie has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Dr. Dimachkie is on the speaker’s bureau or is a consultant for Baxalta, Catalyst, CSL Behring, Mallinckrodt, Novartis and NuFactor. He has received grants from Alexion, Biomarin, Catalyst, CSL-Behring, FDA/OPD, GSK, MDA, NIH, Novartis, Orphazyme and TM. Dr. Barohn has nothing to disclose. Dr. Jawdat has nothing to disclose. Dr. Glenn has nothing to disclose. Dr. Farmakidis has nothing to disclose. Dr. Jabari has nothing to disclose.
Optimized spatial filter mask using genetic algorithm and system identification for modeling sEMG and finger force signals

This paper presents the investigation of the use of System Identification (SI) for modeling sEMG-Finger Force relation in the pursuit of improving the control of prosthetic hands. Finger force and sEMG data is generated by having the subject perform a number of random motions of the ring finger to simulate various force levels. Post-processing of the sEMG signal is performed using spatial filtering. The linear and nonlinear spatial filters are compared based on the 'kurtosis' improvements and also are based on the fit values of the models obtained using system identification. Some of the spatial filter masks are optimized using a Genetic Algorithm (GA) for the constrained and unconstrained cases. The resulting model fit value is utilized to serve as the cost function. The results are compared to the reported filter mask values in the literature. The unconstrained GA based filter mask values and in some instances the constrained GA based mask values performed better than the filter masks reported in literature.
Cognitive Behavioral Treatment of Chronic Insomnia

Cognitive behavior therapy for insomnia (CBT-I) is an evidence-based treatment that has been shown to be an effective treatment for chronic insomnia. Chronic insomnia occurs frequently and affects about 10 % of the general population, or 30 million individuals in the USA alone. Furthermore, insomnia is unlikely to spontaneously remit and its impact on the daytime functioning is significant. Insomnia is a risk factor for medical and psychiatric comorbidity as well as impaired work and social performance. Short-term efficacy of CBT-I has been shown to be comparable to sedative-hypnotic medication and CBT-I treatment effects have been shown to be more durable than sedative-hypnotic medication at follow-ups of up to 2 years. The basic components of CBT-I include sleep restriction, stimulus control, and sleepy hygiene interventions. Adjunctive treatments may include relaxation therapy, phototherapy, and cognitive therapy. A step-by-step description of how treatment is delivered is provided as well as behavioral recommendations for primary care patients.