cssi/SciSciGPT-SciSciNet huggingface dataset:
Sparse X-ray CT image reconstruction and blind beam hardening correction via mass attenuation discretization

We develop a nonlinear sparse X-ray computed tomography (CT) image reconstruction method that accounts for beam hardening effects due to polychromatic X-ray sources. We adopt the blind scenario where the material of the inspected object and the incident polychromatic source spectrum are unknown and apply mass attenuation discretization of the underlying integral expressions that model the noiseless measurements. Our reconstruction algorithm employs constrained minimization of a penalized least-squares cost function, where nonnegativity and maximum-energy constraints are imposed on incident spectrum parameters and negative-energy and smooth l1-norm penalty terms are introduced to ensure the nonnegativity and sparsity of the density map image. This minimization scheme alternates between a nonlinear conjugate-gradient step for estimating the density map image and an active set step for estimating incident spectrum parameters. We compare the proposed method with the existing approaches, which ignore the polychromatic nature of the measurements or sparsity of the density map image.
Further complexity reduction of parallel FIR filters

Based on recently published low complexity parallel FIR filter structures, this paper proposes a new scheme to further reduce their hardware complexity. A FIR filter is firstly transformed into linear convolution, which is then implemented by the iterated short convolution algorithm. This linear convolution structure for FIR filter is used as a processing core to implement the subfilters of previously proposed parallel FIR filter structures. A large amount of hardware can be saved by the new scheme. For example, for a 576-tap FIR filter, when the parallelism level changes from 12 to 72, the new scheme can save 1755 to 3375 multiplications at the cost of 21 to 4658 additions and 1516 to 4749 delay elements, respectively.
Household Cleaning Product-Related Injuries Treated in US Emergency Departments in 1990 -2006

OBJECTIVE: The goal was to examine comprehensively the patterns and trends of household cleaning product-related injuries among children treated in US emergency departments. METHODS: Through use of the National Electronic Injury Surveillance System database, cases of unintentional, nonfatal, household cleaning product-related injuries were selected by using product codes for drain cleaners, ammonia, metal polishes/tarnish removers, turpentine, dishwasher detergents, acids, swimming pool chemicals, oven cleaners, pine oil cleaners/disinfectants, laundry soaps/detergents, toilet bowl products, abrasive cleaners, general-purpose household cleaners, noncosmetic bleaches, windshield wiper fluids, caustic agents, lye, wallpaper cleaners, room deodorizers/fresheners, spot removers, and dishwashing liquids. Products were categorized according to major toxic ingredients, mode of action, and exposure. RESULTS: An estimated 267 269 children ≤5 years of age were treated in US emergency departments for household cleaning product-related injuries. The number of injuries attributable to household cleaning product exposure decreased 46.0% from 22 141 in 1990 to 11 964 in 2006. The product most-commonly associated with injury was bleach (37.1%). Children 1 to 3 years of age accounted for 72.0% of cases. The primary mechanism of injury was ingestion (62.7%). The most common source or container was spray-bottles (40.1%). Although rates of household cleaner-related injuries from regular bottles or original containers and kitchenware decreased during the study period, spray-bottle injury rates showed no decrease. CONCLUSION: Although national rates of household cleaning product-related injuries in children decreased significantly over time, the number of injuries remains high.
Hydrolysis and sulfation pattern effects on release of bioactive bone morphogenetic protein-2 from heparin-based microparticles

Glycosaminoglycans (GAGs) such as heparin are promising materials for growth factor delivery due to their ability to efficiently bind positively charged growth factors including bone morphogenetic protein-2 (BMP-2) through their negatively charged sulfate groups. Therefore, the goal of this study was to examine BMP-2 release from heparin-based microparticles (MPs) after first, incorporating a hydrolytically degradable crosslinker and varying heparin content within MPs to alter MP degradation and second, altering the sulfation pattern of heparin within MPs to vary BMP-2 binding and release. Using varied MP formulations, it was found that the time course of MP degradation for 1 wt% heparin MPs was ∼4 days slower than 10 wt% heparin MPs, indicating that MP degradation was dependent on heparin content. After incubating 100 ng BMP-2 with 0.1 mg MPs, most MP formulations loaded BMP-2 with ∼50% efficiency and significantly more BMP-2 release (60% of loaded BMP-2) was observed from more sulfated heparin MPs (MPs with ∼100% and 80% of native sulfation). Similarly, BMP-2 bioactivity in more sulfated heparin MP groups was at least four-fold higher than soluble BMP-2 and less sulfated heparin MP groups, as determined by an established C2C12 cell alkaline phosphatase (ALP) assay. Ultimately, the two most sulfated 10 wt% heparin MP formulations were able to efficiently load and release BMP-2 while enhancing BMP-2 bioactivity, making them promising candidates for future growth factor delivery applications.
NT‐3‐mediated TrkC receptor activation promotes proliferation and cell survival of rodent progenitor oligodendrocyte cells in vitro and in vivo

We have previously described the expression of a functional full-length trkC transcript for neurotrophin-3 (NT-3) receptor in oligodendroglia (OL) cells (Kumar and de Vellis, 1996). To date, the role of NT-3 and its signal transduction cascade in OL remains poorly defined. We report that the NT-3 responsive population of cells in the OL lineage are the progenitor cells and that the addition of NT-3 results in the autophosphorylation of p145TrkC. Furthermore, NT-3-mediated activation of p21ras and mitogen-activated protein kinase (MAPK), extracellular signal-regulated protein kinase2 (ERK2), were also observed in the progenitor OL cells. These protein tyrosine kinase (PTK)-induced responses were sensitive to the presence of K252a, an inhibitor for tyrosine kinase. We have determined that NT-3 promotes progenitor OL cell commitment to enter into S-phase of cell cycle to initiate DNA synthesis, in a manner similar to platelet-derived growth factor-AA (PDGF-AA). NT-3 thus plays a role in cell proliferation when present alone, while augmenting the proliferation capacity of PDGF-AA as indicated by the nuclear binding activity of the transcription factor, E2F-1. Both the initiation and progression of mitotic events were confirmed by the expression of c-myc and cdc2 in the presence of NT-3, PDGF-AA or NT-3 plus PDGF-AA. A cell survival assay examining interleukin 1-beta-converting enzyme (ICE)-like protease-mediated cleavage of poly (ADP-ribose) polymerase (PARP) revealed an increase in OL progenitor cell death in the absence of NT-3 or PDGF-AA. In corroboration with our in vitro studies, in vivo results show an increased expression of the progenitor OL cell marker, glycerol phosphate dehydrogenase (GPDH) within 48 hr following an intracranial injection of NT-3, PDGF-AA, or NT-3 plus PDGF-AA in PN4-5 rats. These novel findings suggest that PDGF-AA potentiates the OL progenitor cell's ability to enter into the S-phase of the cell cycle and that NT-3 can augment this activity. Furthermore, PDGF-AA and NT-3 can block ICE-like protease-mediated PARP fragmentation in progenitor OL cells. These results provide important information which further delineates the signal transduction cascades and the role of NT-3 and PDGF-AA on OL progenitor cells.
Structure of the fifth EGF-like domain of thrombomodulin: An EGF-like domain with a novel disulfide-bonding pattern.

Abstract The structure of the fifth EGF-like domain (residues Q387 to E426) of thrombomodulin (TMEGF5) has been determined by two-dimensional NMR. TMEGF5 binds to thrombin with a Ki of 1.9 μM and has been shown to have a novel disulfide bonding pattern in a fully active fragment of TM. In EGF, the disulfide bonding pattern is (1-3,2-4,5-6), while TMEGF5 has an uncrossed (1-2,3-4,5-6) pattern. The structure of this novel domain, determined from 483 NOE-derived distance restraints, appears to have diverged from the common EGF-like structure. Superposition of the 14 lowest-energy structures of TMEGF5 gives an overall r.m.s.d. of 1.09 A for the backbone atoms. The central two-stranded β-sheet common to all EGF-like domains is not present in TMEGF5. The A loop, residues C390 to C395, is twisted away from interacting with the B loop, residues C399 to C407, as in EGF, and is close to the C loop, residues C409 to C421. This twist causes the N and C termini to be closer together in TMEGF5 than in EGF. Most of the residues that are important for activity lie on one face of the molecule, which is likely to be the thrombin-binding surface of the domain. The structure of the C loop within the domain, which is a β-hairpin similar to EGF, is similar to the structure of a synthetic version of the loop bound to thrombin as determined by transferred NOE experiments. Despite the similarity in the structures of the loops, the residues immediately following C421 are in different positions in the two structures suggesting that these “tail” residues may change conformation upon thrombin binding.
Care Pathway Guidelines for Assessment and Counseling for Domestic Violence

Family counselors recognize the importance of standards of care and standardized models of evaluation and intervention in cases of domestic violence. Examined is a care pathway guideline developed to ensure consistency in the evaluation and treatment offered where the spectrum of symptoms of domestic violence is identified in the course of screening and counseling. Also provided is a summary of at-risk factors counselors should recognize in screening for abuse, a syndrome often associated with the traumas of domestic violence, and the physical and behavioral indicators of family violence. Issues and import for future care pathway guidelines are offered.
Directing the self-assembly of supra-biomolecular nanotubes using entropic forces

Peptide self-assembly, ubiquitous in biology, is one of the most promising 'bottom-up' approaches for the generation of synthetic supramolecular architectures. However, directing the self-assembly of functional peptides into predictable ordered structures most often requires precise tuning of weak intermolecular forces. Existing strategies are generally based on specific interactions between molecular mediators that require complex chemical synthesis pathways and elaborated design rules. Here we establish a theoretical framework that delineates a generic route towards directing the self-assembly of small peptides by simply using entropic forces generated by the polymer chains attached to the peptides. We demonstrate the viability of this concept for polymer-conjugated peptide nanotubes using coarse-grained molecular dynamics (CGMD) simulations combined with theoretical calculations. We show that conjugated polymer chains create an entropic penalty due to chain confinement upon assembly, and illustrate that the self-assembly process can be directed by merely varying the degree of polymer conjugation. Specifically, the entropic penalty, and consequently, the binding energy between peptides can be greatly varied by changing the length and the number of conjugated polymers. Extending this concept for peptides with different degrees of conjugation reveals a path towards controlling the stacking sequence of binary mixtures. Remarkably, we find that a large disparity in the conjugation degree of the two peptides results in a preference towards alternating mixed sequences that minimize the entropic penalty of confinement in the thermodynamic limit. Our study explains recent experiments on polymer-peptide conjugates and sets the stage for utilizing entropic forces to guide the stacking sequence of functional macrocycles in tubular assemblies.
Physical Properties and Stability of Continental Slope Deposits, Northwest Gulf of Mexico

ABSTRACT Sediments from the continental slope and shelf edge in the northwest Gulf of Mexico were tested to determine their strength, stability, and consolidation characteristics. Consolidation tests for Sabine River delta samples and abyssal plain samples were used to aid in the interpre tation of the shelf and slope samples. To approximate in situ conditions, a direct shear-test machine was used to measure shear strength, and an Anteus Back-Pressure Consolidometer was used to determine consolidation. The topography of this area has been attributed to local slumping of unconsolidated and unstable marine sediments. Although the Sabine River delta samples were underconsolidated, the continental shelf and slope samples were all overconsolidated. The overconsolidation of these samples and the high values of shear strength are assumed to be the result of low deposition rates and incipient cementation of the mineral grains. Analysis of the void ratio versus log-pressure consolidation curves indicated that the sediments were "sensitive," and therefore, relatively undisturbed by the sampling process. The shear strength ranged from 0.05 TSF for the upper meter of sediment to over 0.5 TSF for a simulated depth of 20 meters. The shear strength tests indicate that the slope sediments should be stable to great thicknesses on even higher slopes than exist in this area.
CHEMICAL CHARACTERIZATION OF PERSISTENT IMMUNOREACTIVE GLUCAGON IN EVISCERATED RATS

Extraction of rat submaxillary salivary glands and ileal mucosa yielded a single immunoreactive glucagon component of 25,000 daltons and a major peak of approximately 9,000 daltons respectively. Eviscerated rats with and without functional livers were found to have decreased, but persistent levels of immunoreactive glucagon and total immunoreactive glucagon, as measured with a pancreatic specific and cross reacting antiserum respectively. Gel filtration of serum samples on Sephadex G-50 fine and G-200 superfine demonstrated that there was no measurable 3485, 9000 or 25,000 dalton glucagon immunoreactivity. The persistent immunoreactive glucagon in the serum of eviscerated rats is a heterogeneous mixture of nonspecific materials and does not contain submaxillary or intestinal glucagon-related materials. These findings suggest caution in the interpretation of glucagon immunoreactivity in serum and demonstrate the necessity for chromatographic analysis of circulating IRG.
The Effects of Spectral Power Distribution and Illuminance Levels on Key Parameters in the Male Golden Hamster and Rat With Preliminary Observations on the Effects of Pinealectomy

Three different light sources were used to determine the effects of spectral power distribution (SPD) and illuminance levels on growth and organ weights of male golden hamsters and rats. SPD had little effect on organ weights or measurements of either rats or hamsters. However, responses to illuminance levels were quite apparent, provided they were equalized for the scotopic eye sensitivity curve characteristic of nocturnal animals. Under seven illuminance levels from 0 to 3.9 scotopic fc, hamsters demonstrated graded responses in gonadal weights and presumed function from 0 to 0.02 scotopic fc. Above this level, photopic saturation was apparent. The neuroendocrine system of pinealectomized animals failed to show sensitivity to illuminance levels. The suggestion is made that the pineal gland acts to monitor illuminance levels (below about 0.02 scotopic fc) as well as photic duration. While the latter appears to be an "all or none" effect, the former appears to be graded.
A welfare simulation of mixed-member electoral systems

This paper considers welfare properties of mixed-member electoral systems. In a mixed system, voters may elect high-quality district representatives without excessive campaign fundraising. Simulation results reveal that the optimally mixed electoral system can be welfare-enhancing, but a poorly targeted electoral reform can do worse than a PR system or plurality rule.
Chasing myocardial outcomes: perioperative myocardial infarction and cardiac troponin

Perioperative myocardial infarction represents the most common cardiovascular complication following non-cardiac surgery, but frequently presents without the usual clinical signs and symptoms consistent with acute coronary syndrome. Given the silent nature of this event, a clinician's reliance on risk stratification tools and cardiac specific biomarkers to assist in the identification of at-risk individuals is heightened in the perioperative setting. Although cardiac troponin elevations following non-cardiac surgery have been consistently linked to increased mortality, uncertainty remains over how to clinically intervene to prevent harm. This decision is further complicated by the increasing sensitivity of the newest generation of cardiac biomarker immunoassays. In this narrative review, the growing body of evidence surrounding cardiac troponin elevations in the perioperative setting, how the evidence has been integrated into recent clinical practice guidelines, and its implications for the detection of perioperative myocardial infarction are discussed.
Burn injury differentially alters whole-blood and organ glutathione synthesis rates: An experimental model.

Previous studies from our laboratories revealed a reduced rate of whole-blood (WB) glutathione (GSH) synthesis in severely burned patients. To determine whether WB GSH metabolism is an indicator of the status of GSH metabolism in one or more of the major organs, we used a burn rabbit model to determine GSH concentrations and rates of synthesis in WB, liver, lungs, kidney, and skeletal muscle. L-[1-13C]-cysteine was infused intravenously for 6 h in rabbits at 3 days post-burn and in sham burn controls. WB and organ 13C-enrichment of cysteine and GSH was determined by gas chromatography/mass spectrometry. Plasma cysteine metabolic flux was increased significantly (P < 0.01) following burn injury. WB, liver, and lung GSH concentrations (P = 0.054, P < 0.05, and P < 0.05, respectively) and fractional rates of GSH synthesis (P < 0.05, P < 0.01, and P < 0.05, respectively) were reduced at 3 days post-burn. Kidney was unaffected. There also appears to be an increased rate of GSH transport out of the liver after burn injury. Hence, there is a differential impact of burn injury on tissue and organ GSH status, with WB qualitatively reflecting the changes in lung and liver. It will be important to determine whether these changes are due to alterations in the intrinsic capacity for GSH synthesis and/or availability of amino acid precursors of GSH.
Ultradian rhythms of autonomic, cardiovascular, and neuroendocrine systems are related in humans

Autonomic, cardiovascular, and neuroendocrine activities were monitored for 5-6 h in 10 normal adult resting humans (8 males, 2 females). The nasal cycle, a measure of lateralized autonomic tone, was measured at 4 Hz. Impedance cardiography (BoMed NCCOM3) was used to measure cardiac output, thoracic fluid index, heart rate, ejection velocity index, stroke volume, and ventricular ejection time (averages of 12 heart beats). Systolic, diastolic, and mean arterial pressures were measured with an automated cuff at 7.5-min intervals. Separate blood samples were taken every 7.5 min simultaneously from both arms with the use of indwelling venous catheters. Assays for adrenocorticotropic hormone, luteinizing hormone, norepinephrine, epinephrine, and dopamine were performed on samples from each arm. Time-series analysis, using the fast orthogonal search method of Korenberg, was used to detect variance structure. Significant spectral periods were observed in five windows at 220-340, 170-215, 115-145, 70-100, and 40-65 min. The greatest spectral power was observed in the lower frequencies, but periods at 115-145, 70-100, and 40-65 min were common across variables. Significant correlation coefficients for linear regressions of all paired variables in each subject were observed in 38.87% of the comparisons (subject range, 18.05-48-9.70%) with r > 0.30. These results suggest that either a common oscillator (the hypothalamus) or mutually entrained oscillators regulate these systems.
Distributed Analogical Idea Generation with Multiple Constraints

Previous work has shown the promise of crowdsourcing analogical idea generation, where distributing the stages of analogical processing across many people can reduce fixation, identify inspirations from more diverse domains, and lead to more creative ideas. However, prior work has only considered problems with a single constraint, while many real-world problems involve multiple constraints. This paper contributes a systematic crowdsourcing approach for eliciting multiple constraints inherent in a problem and using those constraints to find inspirations useful in solving it. To do so we identify methods to elicit useful constraints at different levels of abstraction, and empirical results that identify how the level of abstraction influences creative idea generation. Our results show that crowds find the most useful inspirations when the problem domain is represented abstractly and constraints are represented more concretely.
Food, ingestion rates, and assimilation in the desert millipede Orthoporus ornatus (Girard) (Diplopoda).

Orthoporus ornatus feeds mostly on dead plant material and on superficia tissue of desert shrubs. Sand, small particles of rock, and parts of arthropods are also ingested. Millipedes could not be induced to feed in the absence of moist soil in the laboratory after an initial day of feeding.Field observations of apparent food preferences were made at several sites in the southwestern U.S. Millipedes at Big Bend National Park, Texas, fed regularly on bark of the following desert shrubs: cholla (Opuntia sp.), cresotebush (Larrea divaricata), and ocotillo (Fouqueria splendens). Millipedes on the West Mesa of Albuquerque, New Mexico, fed mostly on superficial tissues of dead Russian-thistle (Salsola kali). At the Jornada Validation Site, Dona Ana County, New Mexico, millipedes fed regularly on the bark of Mormon tea (two Ephedra spp.) and mesquite (Prosopis glandulosa). Otherwise, grazing on an assortment of surface litter was commonly observed.Ingestion rates and assimilation efficiencies were determined in the laboratory for millipedes feeding on Prosopis and Ephedra using an ash-free technique. Assimilation efficiencies and ingestion rates were temperature dependent, increasing with a rise in temperature. Ingestion rates for Ephedra ranged from 0.020 to 0.050 g ash-free dry wt per g dry wt tissue per day, with assimilation efficiencies ranging from 20-37%. Ingestion rates were lower for Prosopis than for Ephedra.Feeding experiments at 24° C were considered to depict feeding characteristics found in surface millipedes under field conditions. These millipedes ingested 0.034 g ash-free dry weight of Ephedra per g dry body weight per day with 31.4% of the food being assimilated.No significant differences occurred between assimilation efficiencies calculated by ash-free techniques and by using caloric values of food and feces.
EDOXABAN VERSUS WARFARIN IN 841 PATIENTS WITH ATRIAL FIBRILLATION AND PERIPHERAL ARTERIAL DISEASE: INSIGHTS FROM THE ENGAGE AF-TIMI 48 TRIAL

Peripheral arterial disease (PAD) is associated with ischemic and bleeding risk. The balance of efficacy and safety of various antithrombotics in pts with atrial fibrillation (AF) and PAD is unclear. We compared edoxaban and warfarin in pts with AF and PAD. ENGAGE AF-TIMI 48 randomized 21,105 pts
Survey on the HIV-1 drug resistance threshold in Kunming Yunnan in 2011

Objective The purpose of this research was to study the HIV drug resistance threshold in Kunming city in 2011. Methods From January to September 2011, consecutive blood specimens were collected from 82 newly diagnosed HIV-positive patients with age between 16 and 25. Following the HIV drug resistance threshold surveillance(HIVDR-TS) recommended by WHO, HIV-1 genotypes and the prevalence of transmitted drug resistance were analyzed. Results Fifty-four specimens were successfully amplified and sequenced. Among the qualified 41 sequences, 18(43.9%) were CRF07_BC, 16(39.0%) were CRF08_BC, and 7(17.1%) were CRF01_AE. Only 1 of 41 genotyped specimens had mutation associated with drug resistance(T69D) in the reverse transcriptase gene. The results indicated that the prevalence of transmitted HIVDR was below 5% in Kunming. Conclusion The prevalence of transmitted HIVDR was low in Kunming as determined the using threshold surveillance methods, and HIVDR-TS should be performed periodically.
Patch Graft Urethroplasty: A Review with Emphasis On Use for Strictures in the Region of the Membranous Urethra

Abstract A series of 40 patch graft urethroplasties is presented. The surgical technique, versatility of the procedure and its application to repair of strictures in the membranous urethra are discussed.
Collective Action to Avoid Catastrophe: When Countries Succeed, When They Fail, and Why

This article is concerned with situations in which avoiding a catastrophic outcome requires collective action. Using the logic of simple game theory, I identify circumstances that would cause rational players to act so as to guarantee that a catastrophe occurs, even when it is in their collective interests to avoid such an outcome – and when these players have the means at their disposal to ensure that such an outcome is avoided. I also identify circumstances that would cause rational players to act in concert to avert a catastrophe, and explain why other circumstances that might seem relevant to explaining these outcomes may be entirely inconsequential. Most of my discussion focuses on climate change. However, I also explain the relevance of the approach to three other areas: the millennium bug, drug resistance and nuclear arms control. In the final sections I discuss whether and how institutions might be designed to overcome, or at least reduce the likelihood of, catastrophic collective-action failures at the international level.
Toxic epidermal necrolysis

Toxic epidermal necrolysis (TEN) is a rare but life-threatening disorder of children and adults in which the skin peels off in sheets and mucosal surfaces slough. It is best viewed as a severe form of erythema multiforme, with even more extreme involvement than one sees with the Stevens-Johnson syndrome (SJS). However, the distinction between TEN and SJS is not clear, as there are a number of overlapping definitions. TEN usually represents an idiosyncratic hypersensitivity to a medication, but may result from a variety of infections, or have no clear linkage. Sulfonamide antibiotics, barbiturates, carbamazepine, and allopurinol seem to be the most common offending agents. TEN usually has an acute onset one to three weeks after ingestion of the offending drug. TEN requires distinction from staphylococcal scalded skin syndrome, as treatment is different.
Transporters and Channels

For most of the past century, transporters and ion channels have been the object of many physiological, genetic, biochemical, biophysical, and bioinformatic investigations that have provided a wealth of data about how molecules and ions cross biological membranes (see Chapter 6). In recent years they have also become the subject of structural biology, as a few high-resolution structures have added details from a rich vein of structure–function relationships. The award of the 2003 Nobel Prize to Peter Agre and Rod McKinnon for the x-ray structures of aquaporin (AQP) and the potassium channel brought wide attention to the progress in this field. This chapter presents examples that have varied histories, from the long-studied lactose permease encoded by the lacY gene in the lac operon to a relative newcomer, the water channel AQP. TRANSPORTERS Transport proteins are required for all cells to take up nutrients and to dispose of waste materials, as well as to mediate flux of metabolites between intracellular compartments of eukaryotes. In the cell envelope of Gram-negative bacteria, transport across the outer membrane is facilitated by porins that contain water-filled channels with varying specificity for solutes (see “Porins” in Chapter 5). In contrast, transport proteins of the inner membrane tend to be highly specific for their substrates, and consequently the cell has many diverse transporters in this membrane. Lactose permease and the glucose-3-phosphate transporter of E. coli are examples of specific inner membrane transport proteins, both of whose x-ray crystal structures were reported in 2003.
Optimal Control for Mathematical Models of Tumor Immune System Interactions

In this chapter, we consider the second major feature of the tumor microenvironment: interactions between the tumor and the immune system. Fundamental principles that have already been outlined in the introduction (see Section 1.3.4) will be expanded upon in this chapter. As a vehicle for the analysis we use the classical model by Stepanova [303] and some of its modifications that have been developed in the literature. This model captures the main features that we want to discuss here—immune surveillance and tumor dormancy—and, at the same time, being low-dimensional and minimally parameterized, has the advantage of allowing us to easily visualize associated geometric features (regions of attractions, stability boundaries, etc.). We formulate an optimal control problem whose objective to be minimized is tailored to the inherent multi-stable structure that these systems have. These problems are considered under chemotherapy and under combinations of chemotherapy with a rudimentary form of an immune boost.
Long-term and midterm outcomes of laparoscopic sleeve gastrectomy versus Roux-en-Y gastric bypass: a systematic review and meta-analysis of comparative studies

Abstract Objective This study aimed to compare midterm and long-term weight loss and resolution of co-morbidity with laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic sleeve gastrectomy (LSG). Summary LRYGB and LSG are the most common procedures performed in bariatric surgery. However, their weight loss efficacy in the midterm and long-term has not been well compared. Methods A meta-analysis was performed by systematically identifying comparative studies conducted until the end of June 2016 that investigated weight loss outcome and resolution of co-morbidities (type 2 diabetes mellitus, hypertension, hyperlipidemia, hypertriglyceridemia, and obstructive sleep apnea) with LRYGB and LSG in the midterm (3–5 years) and long term (≥5 years). The primary endpoint was weight loss after LRYGB versus LSG. The secondary endpoint was resolution of co-morbidities after these procedures. Results Fourteen studies comprising 5264 patients were eligible. Follow-up ranged from 36 months to 75.8±8.4 months. The pooled result for weight loss outcomes did not show any significant difference in midterm weight loss (standardized mean difference=-0.03; 95% confidence interval (CI), -0.38–.33; P = .88) but a significant difference in the long-term weight loss outcome favoring LRYGB (standardized mean difference=.17; 95% CI, .05–.28; P = .005). The pooled results demonstrated no significant difference for resolution of type 2 diabetes mellitus, hypertension, hyperlipidemia, and hypertriglyceridemia. Conclusion Despite the insignificant difference between LRYGB and LSG in midterm weight loss, LRYGB produced better weight loss in the long-term. There was no significant difference between the 2 procedures for co-morbidity resolution.
Somnolence: The Silent Partner in the Sleep Apnea-Hypertension Relationship.

See related article, pp 1264–1270 Evidence implicating obstructive sleep apnea (OSA) in blood pressure elevation is compelling, such that OSA is acknowledged as a risk factor in the major guidelines for prevention and management of hypertension.1,2 Nevertheless, not every patient with OSA will develop comorbid hypertension. Traditional markers of disease severity, such as apnea–hypopnea index and degree of nocturnal desaturation, as well as coexisting conditions, including obesity and old age, have been implicated as determinants of enhanced vulnerability.3 More recently, excessive daytime sleepiness (EDS), a common but not pervasive symptom of OSA, has emerged as a nonconventional indicator for identifying high-risk OSA subjects. However, the available literature on the prognostic role of hypersomnolence for clinical outcomes, including hypertension, is controversial.4,5 This discrepancy may be ascribed to the various approaches used to determine EDS, as suggested by Ren et al6 in this issue of Hypertension . These investigators examined the association between prevalent hypertension and EDS in a large, well-characterized Chinese population. The sample consisted of referrals to the sleep clinic for suspected OSA, which was assessed by in-laboratory polysomnography. The use of the gold standard diagnostic method for OSA, in lieu of questionnaires or portable monitors, is a strength of the article. Another important feature is the dual assessment of sleepiness performed in the study. All subjects completed a self-report measure (Epworth Sleepiness Scale7) and a sleep laboratory test (Multiple Sleep Latency Test [MSLT]8) and were then classified based on the average sleep latency (the time taken to fall asleep) exhibited at the MSLT, as an index of EDS. The MSLT consists of 4 to 5 nap opportunities spread across the …
Amyloidosis Presenting with Platelet Dysfunction and Recurrent Retroperitoneal Hemorrhage (RH).

Abstract CASE REPORT: A 59-year-old white female with history of easy bruising for 2 years and 2 episode of RH in the last 6 month admitted to ICU with her 3rd episode of RH. Her previous w/o included a BM Bx which had shown clonal population of plasma cells kappa chain restrictive (7%) with repeatedly negative SPEP and UPEP. PFA-100 was consistent with severe platelet dysfunction. During the ICU admission platelet transfusion with multiple single donor units did not correct her PFA-100 results, which were confirmed with platelet aggregation results. Both, collagen/epinephrine and collagen/ADP closure times were prolonged (>300 and 128 seconds respectively). The patient however did not receive any medications to explain this apparently intrinsic dysfunction. Coagulation studies including PT, aPTT and factor II, VII, VIII, IX all were within normal limit. Factor X levels were slightly decreased (45%). Patient had selective embolization of the fourth lobar artery of the right kidney. Plasma cells in the marrow showed monoclonal expression for cytoplasmic kappa light chains by both IHC and in situ hybridization. Amorphous pink material was present in the walls of blood vessels. Plasma cells stained positively with CD138. The amyloid material stained positively with Congo red and demonstrated apple green birefringence under polarized light. Skeletal survey demonstrated multiple lytic lesions. Serum free light chain measurement showed high levels of M protein (κ) with κ to λ ration of 4.30. Patient was started on treatment with pulse dose steroid and bortezomib. DISCUSSION: Amyloidosis can cause hemorrhage with multiple mechanisms including amyloid deposition (amyloid angiopathy), platelet dysfunction, coagulation factor deficiencies, abnormal fibrin polymerization and hyperfibrinolysis. Consumption of factor X by amyloid is often called a culprit for hemorrhage in amyloidosis. The slightly decreased level of factor X in this case provided a valuable clue for diagnosis, but was not likely a cause of bleeding in this patient. Amyloid induced platelet dysfunction along with amyloid angiopathy lead to life threatening hemorrhage in our patient. The mechanism of this platelet dysfunction, which also affected the transfused platelets, is not well explained. This effect on platelets complicates the clinical management. The case also illustrates the value of the free light chain assay, which is more sensitive than SPEP and UPEP. These commonly used tests to diagnose plasma cell dyscrasias are reportedly false negative in 3% of cases. CONCLUSION: Plasma cell dyscrasia has a wide variety of presentation and should be considered as a part of bleeding work up in complex cases.
490. Electroporation-Mediated Gene Transfer of Caveolin-1 Protects from Bleomycin-Induced Pulmonary Fibrosis Through Regulating Activation of Inflammasome

Pulmonary fibrosis (PF) is a progressive chronic interstitial lung disease associated with high morbidity and mortality. It is characterized by increased deposition of extracellular matrix proteins and the accumulation of scar tissue in the lung interstitium, resulting from alveolar epithelial injury and the accumulation of inflammatory cells. Currently, there is no effective therapy. Gene therapy is a promising approach to treat a variety of lung diseases, including pulmonary fibrosis. Caveolin-1 (Cav-1) is a major component of caveolae, and has been found greatly reduced expression in the lungs of PF patients. Moreover, Cav-1-deficient mice develop spontaneous pulmonary fibrosis. To investigate if Cav-1 can protect from bleomycin-induced pulmonary fibrosis, we delivered plasmids expressing Cav-1 driven by the ubiquitin promoter using electroporation. PF was induced 2 days after gene transfer by intratracheal administration of bleomycin (2 unit/kg). We found that electroporation-mediated gene transfer of Cav-1 to the lung significantly protected from subsequent bleomycin-mediated fibrogenesis by histological analysis and the expression of alpha-smooth muscle actin (alpha-SMA) and collagen measurement. We also found attenuated recruitment of neutrophils and monocytes and/or macrophages in bronchoalveolar lavage (BAL) fluid after gene transfer of Cav-1 compared with vector control. The underlying mechanism was associated with reduced activation of the inflammasome by determining the expression of cleaved caspase-1 and IL-1 beta in both mouse models and cultured cells after overexpression of Cav-1. These results demonstrate that Cav-1 might be a potential target for treatment of pulmonary fibrosis.
Path of translational discovery of urological complications of obesity and diabetes

Diabetes mellitus (DM) is a prevalent chronic disease. Type 1 DM (T1DM) is a metabolic disorder that is characterized by hyperglycemia in the context of absolute lack of insulin, whereas type 2 DM ...
Catalyst Deactivation in Pyridine-Assisted Selective Dehydration of Methyl Lactate on NaY

Acrylic acid is a major commodity chemical currently produced almost entirely from petroleum-derived sources. The catalytic dehydration of methyl lactate is a promising renewable route to producing this vital chemical feedstock; however, enhancing the selectivity toward the dehydration pathway and catalyst stability remain challenging. We demonstrate a selectivity for dehydration products of ∼90% over a period of 30 h on NaY by introducing a small amount of pyridine in the reactant feed (pyridine/methyl lactate = 1:10). This increase in selectivity is attributed to the inhibition of side pathways, i.e., decarbonylation and coking, both of which are catalyzed by surface Bronsted acid sites generated in situ, rather than the acceleration of the dehydration pathway. Catalyst deactivation is shown to proceed through a drastically different mechanism in the absence and presence of pyridine in the feed via a combination of activity tests, thermogravimetric analysis, N2, and transmission FTIR spectroscopic inves...
Pathogenesis of Idiosyncratic Drug Induced Liver Injury

Abstract Drug induced liver injury (DILI) is an important cause of liver injury and the leading cause of acute liver failure (ALF) in the United States. In fact, more than half of all ALF cases in the United States are a result of DILI, most of which are due to acetaminophen ( Lee, 2003 ; Reuben et al., 2010 ). DILI is also the principal reason for failures in clinical drug development and regulatory actions against drugs in development, restrictions for indication, and withdrawal from the market ( Watkins and Seeff, 2006 , Chen et al., 2013 ). DILI is divided into two categories: direct hepatotoxicity and idiosyncratic. Although certain drugs such as acetaminophen, aspirin, and chemotherapeutic agents do cause predictable, dose-dependent and direct hepatotoxicity, most instances of liver injury from drugs are idiosyncratic. Idiosyncratic drug induced liver injury (IDILI) is unpredictable with a relatively long latency and occurs only in a small proportion of exposed individuals. Hepatotoxicity presents with a spectrum of clinical signatures such as cholestatic liver injury, hepatitis, nodular regenerative hyperplasia, steatohepatitis, and sinusoidal obstruction syndrome as examples. Phenotypically IDILI is subdivided based on the R ratio which is the alanine transaminase over alkaline phosphatase (multiple of the upper limit of the normal) into cholestatic (≤2), hepatocellular (≥5), and mixed (2–5) patterns of injury. Generally, DILI is a diagnosis of exclusion and common liver disorders such as viral hepatitis, autoimmune hepatitis (AIH), biliary tract disease, ischemic hepatitis, heart failure, and circulatory dysfunction, as well as sepsis and alcoholic liver disease must be ruled out. If all of these are ruled out and a high index of suspicion is present for drug toxicity, and the drug is taken within the correct time frame (latency), and the characteristics of the injury match with the drug's signature (if known), the probability of an IDILI event is high. Allergic features such as eosinophilia, fever, and rash, although less common, may be helpful if present. A liver biopsy can be helpful if eosinophilic infiltrates, granulomas, or centrilobular necrosis is noted. Because there is no specific test to determine causality and even the liver biopsy is often nonspecific, the diagnosis of IDILI remains challenging. Furthermore, IDILI is a complex multifactorial disease, which is not fully understood. In the past decade using large patient cohorts, risk factors associated with the development of IDILI have been identified. Many of these include host polymorphisms that affect adaptive immune responses, which we will explore in more detail.
Improved costs and outcomes with conscious sedation vs general anesthesia in TAVR patients: Time to wake up?

Author(s): Toppen, William; Johansen, Daniel; Sareh, Sohail; Fernandez, Josue; Satou, Nancy; Patel, Komal D; Kwon, Murray; Suh, William; Aksoy, Olcay; Shemin, Richard J; Benharash, Peyman | Abstract: BackgroundTranscatheter aortic valve replacement (TAVR) has become a commonplace procedure for the treatment of aortic stenosis in higher risk surgical patients. With the high cost and steadily increasing number of patients receiving TAVR, emphasis has been placed on optimizing outcomes as well as resource utilization. Recently, studies have demonstrated the feasibility of conscious sedation in lieu of general anesthesia for TAVR. This study aimed to investigate the clinical as well as cost outcomes associated with conscious sedation in comparison to general anesthesia in TAVR.MethodsRecords for all adult patients undergoing TAVR at our institution between August 2012 and June 2016 were included using our institutional Society of Thoracic Surgeons (STS) and American College of Cardiology (ACC) registries. Cost data was gathered using the BIOME database. Patients were stratified into two groups according to whether they received general anesthesia (GA) or conscious sedation (CS) during the procedure. No-replacement propensity score matching was done using the validated STS predicted risk of mortality (PROM) as a propensity score. Primary outcome measure with survival to discharge and several secondary outcome measures were also included in analysis. According to our institution's data reporting guidelines, all cost data is presented as a percentage of the general anesthesia control group cost.ResultsOf the 231 patients initially identified, 225 (157 GA, 68 CS) were included for analysis. After no-replacement propensity score matching, 196 patients (147 GA, 49 CS) remained. Overall mortality was 1.5% in the matched population with a trend towards lower mortality in the CS group. Conscious sedation was associated with significantly fewer ICU hours (30 vs 96 hours, p = l0.001) and total hospital days (4.9 vs 10.4, pl0.001). Additionally, there was a 28% decrease in direct cost (pl0.001) as well as significant decreases in all individual all cost categories associated with the use of conscious sedation. There was no difference in composite major adverse events between groups. These trends remained on all subsequent subgroup analyses.ConclusionConscious sedation is emerging as a safe and viable option for anesthesia in patients undergoing transcatheter aortic valve replacement. The use of conscious sedation was not only associated with similar rates of adverse events, but also shortened ICU and overall hospital stays. Finally, there were significant decreases in all cost categories when compared to a propensity matched cohort receiving general anesthesia.
Two-Level Augmented Definitive Screening Designs

[This abstract is based on the authors' abstract.] Definitive screening designs (DSDs) constitute a well-known class of screening designs for three-level factors. DSDs are comprised of orthogonal main effects plans for which main effects estimates are statistically independent of estimates of two-factor interactions. Jones and Nachtsheim (2013) proposed two methods for augmenting DSDs with two-level categorical factors, namely the DSD-augment and the ORTH-augment approaches. However, these two versions produce distinct features that are not sufficiently flexible to accommodate versatile performance preferences in practice. In this paper, we provide a comprehensive overview of the augmented designs with DSD structures and show how to construct compromise designs that share the desirable traits of both DSD-augment and ORTH-augment designs. In addition to the DSD-augment and ORTH-augment designs, we suggest routine consideration of nondominated compromise designs as described in the paper. Additionally, we provide some theoretical properties of randomly assigned augmented DSDs.
Performance during competition and competition outcome in relation to testosterone and cortisol among women

A contribution to a special issue on Hormones and Human Competition. This study investigated the relation between competition, testosterone (T), and cortisol (C) in women. One hundred and twenty female participants competed against a male confederate in a computerized laboratory task. The task was preprogrammed so that half the women won and half of the women lost the competition. T and C concentrations were measured in saliva samples collected at four time points before and after the competition. Accuracy and reaction time during the competition were recorded. T and C increased directly after the competition, though not significantly for C, and then decreased over time regardless of the competition outcome. Regression analyses demonstrated that baseline T was significantly and positively associated with competition accuracy, though only in individuals who were low in C. Individuals who were high in C showed no relation between T and accuracy. This relation was further qualified by competition outcome. Losers of the competition showed a significant positive relation between baseline T levels and competition accuracy, though only if they were low in C. No relation was found between T and accuracy in losers who were high in C. Winners of the competition showed no relation between T and accuracy, regardless of whether C levels were high or low. These results are in line with the dual-hormone hypothesis, whereby the effects of T on status-seeking behaviors are dependent on C levels for individuals whose status is threatened.