cssi/SciSciGPT-SciSciNet huggingface dataset:
Trust, Protocol, Gender, and Power in Interwar British Biomedical Research: Kathleen Chevassut and the "Germ" of Multiple Sclerosis

In March 1930, reports of the discovery of an organism causative of multiple sclerosis circulated in the British press. At the same time, news of a therapeutically efficacious vaccine also reached the ears of neurologists and patients afflicted with the debilitating degenerative disease. It was soon shown that no organism had been discovered. The events leading up to this ultimately painful episode reveal many of the central problems created when social conventions and a sense of decorum scripted received understanding of good scientific practice rather than actual regulatory frameworks. In the absence of such frameworks, few means were present to censor inappropriate scientific conduct. This story thus provides a window into an emergent world of state-sponsored biomedical research; a world where recrimination, gossip, misogyny, uncertainty, exaggeration, and dreams and delusions of scientific and therapeutic progress were collapsed together.
On the construction of preconditioners by subspace decomposition

Abstract A preconditioner for the iterative solution of symmetric linear systems which arise in Galerkin's method is obtained by decomposition of the space into orthogonal subspaces. The preconditioner corresponds to a particular bilinear form and is actually a 2-level multigrid method. Applications are presented to the numerical solution of elliptic problems by the finite-element method and to the numerical solution of first-kind Fredholm integral equations by Tikhonov regularization.
Genetic barriers to resistance and impact on clinical response

The development of drug resistance and cross-resistance continues to pose a challenge to successful long-term antiretroviral therapy despite the availability of new antiretroviral agents. The genetic barrier to resistance of a regimen does not directly correlate with its effectiveness. For some regimens with a low genetic barrier to resistance, however, the emergence of only 1 or 2 key resistance mutations may confer drug resistance not only to that regimen but also to other agents, thereby limiting subsequent treatment options. In addition to the genetic barrier to resistance, factors such as efficacy, safety, tolerability, convenience, and adherence must be considered when choosing a regimen.
Managing therapeutic despair.

CASE REPORT Ms. A., a 22-year-old single white woman, has been on locked units of various private and public hospitals continuously since the age of 16. Her diagnoses are major depression - recurrent, posttraumatic stress disorder, and mixed eating disorder on Axis I; and borderline personality disorder on Axis 11. The patient is the youngest of six children born to an unemployed alcoholic mother. She has never known her biologic father. She reports that as an infant she was left in an unheated apartment, often with no food, for hours at a time. At the age of 2 she fell off the second-story porch of her home but was not medically evaluated. She was electively mute from ages 3 to 7. During her early childhood she was left in the care of a male landlord who allegedly sexually abused her. She also reports having been sexually molested, which included intercourse, by several of her mother’s boyfriends. When the patient was 6 the state child welfare agency removed the children from the mother’s custody after finding that they had been abused and neglected. For the next 10 years the patient often stayed home from school to take care of infants in her foster mother’s unlicensed family care center. At age 14 she reported to her foster mother that the foster mother’s boyfriend had made sexual advances toward her, but the foster mother apparently did not believe the patient. The patient’s eating difficulties (starving, binging, and purging) began shortly thereafter. Beginning at age 14 Ms. A. made several suicidal gestures of varying degrees of lethality, usually by ingesting over-thecounter medication. She was preoccupied with injuring her
Leading Small Molecule Inhibitors of Anti-Apoptotic Bcl-2 Family Members

Anti-apoptotic members of the Bcl-2 protein family are commonly overexpressed in human malignancies, where they contribute to tumorigenesis and the development of resistance to chemo-, radio-, and immunotherapies. Considerable effort is being invested in academic and pharmaceutical settings to identify and design effective small molecule inhibitors of the anti-apoptotic Bcl-2 family members. This chapter will focus on recent advances in the development and application of three small molecule inhibitors (ABT-737, ABT-263, GX15-070), with a particular emphasis on progress that has been made in the evaluation of these compounds in preclinical in vivo models and clinical trials.
Opsoclonus in a patient with increased titers of anti-GAD antibody provides proof for the conductance-based model of saccadic oscillations

Paucity in gamma-amino butyric acid (GABA) due to blockage in the action of glutamic acid decarboxylase (GAD), as seen in the syndrome of anti-GAD antibody, causes adult onset cerebellar ataxia, muscle rigidity, and episodic spasms. Downbeat nystagmus, saccadic dysmetria, impaired ocular pursuit, and impaired cancelation of vestibular ocular reflex are typical ocular motor deficits in patients with syndrome of anti-GAD antibody. We describe opsoclonus, in addition to downbeat nystagmus, in a patient with increased titers of anti-GAD antibody. Paucity in GABA leading to disinhibition to Purkinje target neurons at deep cerebellar and vestibular nuclei might have caused downbeat nystagmus in our patient. Anti-GAD antibody can also increase levels of glutamate the precursor of GABA and the substrate for the action of GAD. We propose that opsoclonus might be due to increased levels of glutamate and subsequent hyperexcitability of excitatory and inhibitory burst neurons leading to reverberation in their reciprocally innervating circuit.
Controversies Regarding Lipid Management and Statin Use for Cardiovascular Risk Reduction in Patients With CKD

Adults with chronic kidney disease (CKD) are at heightened risk for dying of cardiovascular disease. Results from randomized clinical trials of statin drugs versus placebo demonstrate that statin drugs or statin plus ezetimibe reduce the absolute risk for coronary heart disease and mortality among adults with non–dialysis-dependent CKD. The Kidney Disease: Improving Global Outcomes 2013 clinical practice guideline for lipid management in CKD recommends that adults 50 years or older with non–dialysis-dependent CKD be treated with a statin or statin plus ezetimibe regardless of low-density lipoprotein cholesterol levels. However, at least 9 guidelines published during the last 5 years address lipid management for primary and secondary prevention of atherosclerotic cardiovascular disease, and not all guidelines address the utility of lipid-lowering therapy in adults with CKD. Because most patients with CKD receive most of their clinical care from non-nephrologists, differences in recommendations for lipid-lowering therapy for cardiovascular disease prevention may negatively affect the clinical care of adults with CKD and cause confusion for both patients and providers. This review addresses the identification and management of lipid levels in patients with CKD and discusses the existing controversies regarding testing and treatment of lipid levels in the CKD population.
Treatment of one beef animal per herd with permethrin for horn fly control.

Unrestrained cattle were treated on summer pasture with a CO2-propelled hand sprayer operated from a pickup truck by the driver. Treatment of an individual bull, cow, or steer per herd (10–32 head) with permethrin EC spray (0.1–2.0% AI) eliminated all horn flies, Haematobia irritans (L.), from the herds within one day, usually with 90–100% reductions for at least one wk.
Is Marketing Education Drifting

As marketing becomes more scientific in its orientation and methodology, are the collegiate schools of business responding with more rigorous programs or merely drifting along?Here is the available...
The Walnut Husk Fly (Rhagoletis Juglandis Cression)

An infestation of this trypetid in English walnuts in southern California has undoubtedly existed for several years though the correct identity of the insect concerned was not known until the beginning of the 1928 season. It appears to be a potentially serious pest of English walnuts causing the most injury to the later ripening thick-husked commercial varieties. The nature of the injury is described. Notes on life history studies are given with a brief discussion of possible control.
Left in the Genes

Researchers have sought a handedness gene for over a century. The twentieth century saw two basic approaches to this search. Single-gene models propose one genetic locus with several variants ( alleles ) as the major mechanism of inheritance of right- versus left-handedness. These models try to explain both the human population bias toward right-handedness and the handedness patterns observed in families and in samples of identical (MZ or monozygotic) and fraternal (DZ or dizygotic) twins. Some theories were successful in accounting for the observed data while others were not. The second approach argues that handedness is determined by a number of genes but it is also influenced by nongenetic factors both biological and environmental. This paradigm sought to partition the variation in human handedness patterns into genetic and environmental components. The twenty-first century ushered in a shift in research emphasis. Genomic mapping studies seek to relate handedness patterns to specific locations on specific chromosomes. Structural equation models use complex correlational designs to partition the observed handedness variation in twins into genetic and environmental components. Researchers have concluded that there is a biological and probably genetic component to the development of human handedness but this component is not direct but linked to genes affecting body asymmetries and brain development.
19: RESVERATROL IMPROVES INSULIN RESISTANCE WITH ANTI-INFLAMMATORY AND “BROWNING” EFFECTS IN ADIPOSE TISSUE OF OVERWEIGHT HUMANS

Purpose of Study Resveratrol is a plant-derived polyphenol whose beneficial metabolic effects in rodents include improved insulin sensitivity, reduced inflammation, and increased muscle mitochondrial biogenesis. We set out to confirm these findings in insulin resistant human subjects, by examining the effects of resveratrol on insulin sensitivity, muscle mitochondria, and adipose inflammation. Methods Used Specifically, resveratrol 2 gm/day (RV) or placebo (PL) were administered for 28 days in a randomized, double-blinded fashion to n=21 non-diabetic subjects (17 M; Age=52±2; BMI=31.9±0.9 kg/m 2 ; HOMA-IR=3.9±0.2). All subjects participated in 6-hour, stepped euglycemic hyperinsulinemic (30 and 80 mU/m 2 .min) ‘pancreatic clamp’ studies to assess hepatic and peripheral insulin sensitivity, with biopsies of vastus lateralis muscle and subcutaneous abdominal adipose tissue, before and after RV and PL. Muscle mitochondria were analyzed for quantity, size, area in a field, and the % area covered, using electron microscopy with Volocity image analysis. Summary of Results RV induced a 22% (p=0.035) increase in glucose uptake, but did not affect glucose production. There were no changes in quantity (p=0.829) or percent area (p=0.897) of muscle mitochondria. There were no changes in basal or resting energy expenditure (Kcal/day) or respiratory quotient, as assessed by indirect calorimetry (Deltatrac), or in muscle strength in these healthy middle-aged subjects. However, RV reduced adipose tissue inflammation, with decreased expression of the pro-inflammatory cytokines TNFα and IL6 in whole fat (by 68% and 52%, p Conclusions Thus, while improved insulin sensitivity was not accompanied by changes in size or number of muscle mitochondria, anti-inflammatory and ‘browning’ effects in adipose tissue could contribute to resveratrol9s favorable metabolic effects in insulin resistant humans.
Congenital Fiber Type Disproportion Genetics

Novel heterogeneous missense mutations in five families with congenital fiber type disproportion (CFTD) were identified in a study at Children's Hospital at Westmead, University of Sydney, and other centers in Australia, Canada, and France.
Learning periodic motions from human demonstrations using transverse contraction analysis

In this paper, an algorithm called transverse contracting dynamic system primitive (CDSP) to learn the dynamics of periodic motions from demonstrations is presented. Learning motion plans is essential in making robot programming possible by non-expert programmers as well as realizing human-robot collaboration. The complex periodic motion of the human arm is generated by an orbitally stable closed-loop dynamical system. To capture the complexity, a neural network (NN) model is used to represent the dynamics of the human arm motion states. To take into consideration the orbitally stable nature of the human arm motion dynamics, the unknown motion model learning is subjected to transverse contraction analysis constraints. To learn the model parameters, an optimization problem is formulated by relaxing the non-convex transverse contraction constraints using sum of squares (SOS) programming. The NN model is approximated by using a polynomial approximation of the activation function in order to pose the optimization problem as an SOS problem. A negative gradient of a repulsive potential function is added to the learned transverse contracting model to incorporate obstacle avoidance. Experimental results indicate that the model learning via CDSP can generate periodic motions learned from human demonstrated data recorded using Microsoft Kinect sensor. The CDSP algorithm is able to adapt to situations for which the demonstrations are not available, e.g., an obstacle placed in the path. The comparison between the CDSP algorithm and rhythmic dynamic movement primitives (DMPs) shows that the CDSP algorithm performs better in terms of periodic trajectory reproduction accuracy and the time taken by the reproductions to enter the periodic orbit from random initial conditions.
On calculating HR bond enthalpies using computational data

Abstract A method (AIIR) for calculating H R bond enthalpies based on the A verage of several I sogyric and I sodesmic hydrogen abstraction R eactions is discussed and evaluated by comparing calculated values to experimentally determined values for a number of H X bond enthalpies. At the G4 level of theory, the AIIR method calculated H R bond enthalpies with a mean-absolute-deviation (MAD) of 0.5 kcal mol −1 , compared to a MAD of 1.1 kcal mol −1 when the bond enthalpy is calculated directly.
Advertising Localization Overshadows Standardization

ABSTRACT The controversy over the use of standardized advertising campaigns has not been settled. Very little research has examined the role of American and non-American subsidiaries in designing and implementing campaigns for nondomestic markets. This study investigates the attitudes of these executives in two European countries. The findings reveal that almost two-thirds of the subsidiaries use the localized approach and that many major obstacles still impede the standardization of advertising campaigns. The study suggests that the use of similar appeals, symbols, and even themes to target foreign countries is ill advised.
The alcohol-sensitive period during early octavolateral organ development in zebrafish (Danio rerio)

Fetal alcohol exposure can cause Fetal Alcohol Spectrum Disorders (FASD), completely preventable developmental disabilities characterized by permanent birth defects. However, specific gestational timing when developing organs are most sensitive to alcohol exposure is unclear. In this study, we examined the temporal effects of embryonic alcohol exposure on octavolateral organs in zebrafish (Danio rerio), including inner ears and lateral line neuromasts that function in hearing, balance, and hydrodynamic detection, respectively. To determine an alcohol-sensitive period in the first 24 hours post fertilization (hpf), Et(krt4:EGFP)sqet4 zebrafish that express green fluorescent protein in sensory hair cells were treated in 2% alcohol for 2, 3, and 5-hours. Octavolateral organs of control and alcohol-exposed larvae were examined at 3, 5, and 7 days post fertilization (dpf). Using confocal and light microscopy, we found that alcohol-exposed larvae had significantly smaller otic vesicles and saccular otoliths than control larvae at 3 dpf. Only alcohol-exposed larvae from 12-17 hpf had smaller otic vesicles at 5 dpf, smaller saccular otoliths at 7 dpf and fewer saccular hair cells, neuromasts and hair cells per neuromast at 3 dpf. In addition, auditory function was assessed by microphonic potential recordings from inner ear hair cells in response to 200-Hz stimulation. Hearing sensitivity was reduced for alcohol-exposed larvae from 7-12 and 12-17 hpf. Our results show that 12-17 hpf is an alcohol-sensitive time window when morphology and function of zebrafish octavolateral organs are most vulnerable to alcohol exposure. This study implies that embryonic alcohol exposure timing during early development can influence severity of hearing deficits. © 2017 Wiley Periodicals, Inc.
Efficient memory disaggregation with INFINISWAP

Memory-intensive applications suffer large performance loss when their working sets do not fully fit in memory. Yet, they cannot leverage otherwise unused remote memory when paging out to disks even in the presence of large imbalance in memory utilizations across a cluster. Existing proposals for memory disaggregation call for new architectures, new hardware designs, and/or new programming models, making them infeasible. This paper describes the design and implementation of INFINISWAP, a remote memory paging system designed specifically for an RDMA network. INFINISWAP opportunistically harvests and transparently exposes unused memory to unmodified applications by dividing the swap space of each machine into many slabs and distributing them across many machines' remote memory. Because one-sided RDMA operations bypass remote CPUs, INFINISWAP leverages the power of many choices to perform decentralized slab placements and evictions. We have implemented and deployed INFINISWAP on an RDMA cluster without any modifications to user applications or the OS and evaluated its effectiveness using multiple workloads running on unmodified VoltDB, Memcached, PowerGraph, GraphX, and Apache Spark. Using INFINISWAP, throughputs of these applications improve between 4× (0:94×) to 15:4× (7:8×) over disk (Mellanox nbdX), and median and tail latencies between 5:4× (2×) and 61× (2:3×). INFINISWAP achieves these with negligible remote CPU usage, whereas nbdX becomes CPU-bound. INFINISWAP increases the overall memory utilization of a cluster and works well at scale.
Dynamic behavior of thick magnetorheological elastomers

This work is focused on the study of the dynamic behavior of thick magnetorheological elastomers at high frequencies. Experimental and theoretical studies are conducted to investigate the dynamic s...
Aggregated Randomly Generated Math Curriculum-Based Measurements for Middle School Students: Reliability, Predictive Validity, and Cut Score Precision.

Approximately, 283 sixth-grade students completed four randomly generated Math Curriculum–Based Measures (M-CBMs) from interventioncentral.org twice during a fall semester. These M-CBMs measured fo...
The Baptized Muse: Early Christian Poetry as Cultural Authority

(2017). The Baptized Muse: Early Christian Poetry as Cultural Authority. Journal of Early Christian History: Vol. 7, No. 2, pp. 91-95.
A Convex Programming Approach to Transistor Sizing

In Chapter 3, the transistor sizing problem was defined, and various approaches that have been used to tackle this problem were described. The chief shortcoming of most of these approaches, as pointed out in Section 3.7, was that the simplifying assumptions made by these algorithms to make the optimization problem more tractable may lead to a suboptimal solution.
Lycopenes and Related Compounds

Lycopene, a carotene with bright red pigment in ripe red tomatoes, is routinely consumed by humans today. The foods rich in lycopene are usually tomato products, such as, catsup, tomato sources, tomato juice, etc., and some other fruit, such as watermelon. Lycopene can be detected in human circulation and in tissues in both all- trans and cis forms. As a lipophilic antioxidant, it has been demonstrated as one of the most efficient singlet-oxygen-quenchers. Human studies linked intakes of tomato and lycopene and serum or plasma lycopene concentrations to the subsequent development of cancers, reduction of degenerative disease, and reduced risks of cardiovascular disease.
Policing the Lesbian and Gay Community: The Perceptions of Lesbian and Gay Police Officers

This exploratory research conducted in the U.S. examines the workplace views and shared perceptions of lesbian and gay police officers about community policing. Using survey responses from 134 officers and 3 focus group sessions, advantages and disadvantages are identified for lesbian and gay officers and the communities and departments they service. While representative community policing is valued, officers report that cultural competence for officers and good police skills—regardless of sexual orientation—are the most important factors for being an effective officer.
Modeling HPV vaccination scale-up among urban young men who have sex with men in the context of HIV

Abstract Introduction Young men who have sex with men (YMSM) are at high risk to contract human papillomavirus (HPV). While an effective vaccination exists, its use among YMSM is markedly lower compared to non-MSM and women. This study compares scaling up HPV vaccination in conjunction with other prevention strategies. Methods An agent-based model of urban YMSM (≤26 years of age) reflective of the demography of Philadelphia, PA, simulated for up to ten years of follow-up to examine anal and oral transmission of the HPV genotypes covered in the nonavalent (9v) vaccine: 6, 11, 16, 18, 31, 33, 45, 52, 58. Starting HPV prevalences ranged from a high of 18% (type 6) to a low of 6% (type 31); overall 65% of individuals carried any HPV genotype. Simulated levels of vaccination were ranged from 0% to 13% (present-day level), 25%, 50%, 80% (Healthy People 2020 target), and 100% in conjunction with condom use and HIV seroadaptive practices. The primary outcome was the relative reduction in HPV infection. Results Compared to present-day vaccination levels (13%), scaling-up vaccination led to expected declines in 10-year post-simulation HPV prevalence. Anal HPV (any 9v types) declined by 9%, 27%, 46%, and 58% at vaccination levels of 25%, 50%, 80%, and 100%, respectively. Similarly, oral HPV (any 9v types) declined by 11%, 33%, 57%, and 71% across the same levels of vaccine uptake. Comparing the prevention strategies, condoms blocked the greatest number of anal transmissions when vaccination was at or below present-day levels. For oral transmission, vaccination was superior to condom use at all levels of coverage. Conclusions Public health HPV preventions strategies should continue to emphasize the complementary roles of condoms and vaccination, especially for preventing oral infection. Improving vaccination coverage will ultimately have the greatest impact on reducing HPV infection among YMSM.
STUDY OF THE 2007 APRIL 20 CME-COMET INTERACTION EVENT WITH AN MHD MODEL

This study examines the tail disconnection event on 2007 April 20 on comet 2P/Encke, caused by a coronal mass ejection (CME) at a heliocentric distance of 0.34 AU. During their interaction, both the CME and the comet are visible with high temporal and spatial resolution by the STEREO-A spacecraft. Previously, only current sheets or shocks have been accepted as possible reasons for comet tail disconnections, so it is puzzling that the CME caused this event. The MHD simulation presented in this work reproduces the interaction process and demonstrates how the CME triggered a tail disconnection in the April 20 event. It is found that the CME disturbs the comet with a combination of a 180° sudden rotation of the interplanetary magnetic field (IMF), followed by a 90° gradual rotation. Such an interpretation applies our understanding of solar wind-comet interactions to determine the in situ IMF orientation of the CME encountering Encke.
New imaging techniques in colorectal cancer

The ability to visualize biochemical processes in tumor tissues by PET and correlate these findings with anatomic imaging such as CT and MRI gives new insight into the metabolic and physiologic aspects of the tumor tissue. This may permit discrimination between recurrent colorectal carcinoma and some benign lesions. The potential for its use in pharmacology or in monitoring drug therapy is just beginning to be explored. Improvements in acquisition techniques such as whole body imaging, and in methods of absolute quantitation will be important for standardizing image information and making it more widely applicable. Careful evaluation of the impact on patient outcome and clinical decision making are vital in determining the further use of this technology and the planned multicenter trial evaluating cost-effectiveness is welcome step in this direction.
The Quality of Internal Life

So far, in this consideration of quality of life, the focus has been on the social nature of people . Two groups have been considered using their numeric nature, that is, the accretion of information from more than one person, to infer the quality of life in the age of sailing ships. We now turn to internal aspects of the human experience in order to recognize the subjective aspect of quality of life.
RSA key generation: new attacks

We present several new side-channel attacks against RSA key generation. Our attacks may be combined and are powerful enough to fully reveal RSA primes generated on a tamper-resistant device, unless adequate countermeasures are implemented. More precisely, we describe a DPA attack, a template attack and several fault attacks against prime generation. Our experimental results confirm the practicality of the DPA and template attacks. To the best of our knowledge, these attacks are the first of their kind and demonstrate that basic timing and SPA countermeasures may not be sufficient for high-security applications.
Site-specific graph neural network for predicting protonation energy of oxygenate molecules.

Bio-oil molecule assessment is essential for the sustainable development of chemicals and transportation fuels. These oxygenated molecules have adequate carbon, hydrogen, and oxygen atoms that can be used for developing new value-added molecules (chemicals or transportation fuels). One motivation for our study stems from the fact that a liquid phase upgrading using mineral acid is a cost-effective chemical transformation. In this chemical upgrading process, adding a proton (positively charged atomic hydrogen) to an oxygen atom is a central step. The protonation energies of oxygen atoms in a molecule determine the thermodynamic feasibility of the reaction and likely chemical reaction pathway. A quantum chemical model based on coupled cluster theory is used to compute accurate thermochemical properties such as the protonation energies of oxygen atoms and the feasibility of protonation-based chemical transformations. However, this method is too computationally expensive to explore a large space of chemical transformations. We develop a graph neural network approach for predicting protonation energies of oxygen atoms of hundreds of bioxygenate molecules to predict the feasibility of aqueous acidic reactions. Our approach relies on an iterative local nonlinear embedding that gradually leads to global influence of distant atoms and a output layer that predicts the protonation energy. Our approach is geared to site-specific predictions for individual oxygen atoms of a molecule in comparison with commonly used graph convolutional networks that focus on a singular molecular property prediction. We demonstrate that our approach is effective in learning the location and magnitudes of protonation energies of oxygenated molecules.
Optical and photodynamic properties of carbon/TiO2 hybrid dots in different nanoscale configurations

Abstract Carbon/TiO2 hybrid dots with the general configuration of nanoscale carbon domains incorporated with TiO2 nanoparticles of different sizes (8 and 25 nm in diameter) were prepared and characterized, and their optical and photodynamic properties were studied. The properties were found to be affected dramatically by the relative sizes and configurations of the nanoscale carbon domains and TiO2 nanoparticles in the hybrid dots, as reflected by the observed major difference in their photodynamic inactivation of bacteria under visible light. Mechanistic implications of the results are discussed.
Severe Hypoxemia Prevents Spontaneous and Naloxone-induced Breathing Recovery after Fentanyl Overdose in Awake and Sedated Rats

Background As severe acute hypoxemia produces a rapid inhibition of the respiratory neuronal activity through a nonopioid mechanism, we have investigated in adult rats the effects of hypoxemia after fentanyl overdose-induced apnea on (1) autoresuscitation and (2) the antidotal effects of naloxone. Methods In nonsedated rats, the breath-by-breath ventilatory and pulmonary gas exchange response to fentanyl overdose (300 µg · kg · min iv in 1 min) was determined in an open flow plethysmograph. The effects of inhaling air (nine rats) or a hypoxic mixture (fractional inspired oxygen tension between 7.3 and 11.3%, eight rats) on the ability to recover a spontaneous breathing rhythm and on the effects of naloxone (2 mg · kg) were investigated. In addition, arterial blood gases, arterial blood pressure, ventilation, and pulmonary gas exchange were determined in spontaneously breathing tracheostomized urethane-anesthetized rats in response to (1) fentanyl-induced hypoventilation (7 rats), (2) fentanyl-induced apnea (10 rats) in air and hyperoxia, and (3) isolated anoxic exposure (4 rats). Data are expressed as median and range. Results In air-breathing nonsedated rats, fentanyl produced an apnea within 14 s (12 to 29 s). A spontaneous rhythmic activity always resumed after 85.4 s (33 to 141 s) consisting of a persistent low tidal volume and slow frequency rhythmic activity that rescued all animals. Naloxone, 10 min later, immediately restored the baseline level of ventilation. At fractional inspired oxygen tension less than 10%, fentanyl-induced apnea was irreversible despite a transient gasping pattern; the administration of naloxone had no effects. In sedated rats, when PaO2 reached 16 mmHg during fentanyl-induced apnea, no spontaneous recovery of breathing occurred and naloxone had no rescuing effect, despite circulation being maintained. Conclusions Hypoxia-induced ventilatory depression during fentanyl induced apnea (1) opposes the spontaneous emergence of a respiratory rhythm, which would have rescued the animals otherwise, and (2) prevents the effects of high dose naloxone.
Left Ventricular Thrombus Formation in the Setting of Normal Systolic Function.

Abstract We describe the case of a 42-year-old female with recurrent left ventricular (LV) thrombus and multiple embolic events despite having normal LV systolic function. The clinical presentation, associated conditions, diagnostic evaluation and treatment of patients with LV thrombus in the setting of normal LV systolic function are discussed. (Level of Difficulty: Beginner.)
Moderately Inducing Autophagy Reduces Tertiary Brain Injury After Perinatal Hypoxia-Ischemia

Recent studies of cerebral hypoxia-ischemia (HI) have highlighted slowly progressive neurodegeneration whose mechanisms remain elusive, but if blocked, could considerably improve long-term neurological function. We previously established that the cytokine transforming growth factor (TGF)β1 is highly elevated following HI and that delivering an antagonist for TGFβ receptor activin-like kinase 5 (ALK5) -SB505124 - 3 days after injury in a rat model of moderate pre-term HI significantly preserved the structural integrity of the thalamus and hippocampus as well as neurological functions associated with those brain structures. To elucidate the mechanism whereby ALK5 inhibition reduces cell death, we assessed levels of autophagy markers in neurons and found that SB505124 increased numbers of autophagosomes and levels of lipidated LC3 (light chain 3), a key protein known to mediate autophagy. However, those studies did not determine whether 1) SB was acting directly on the CNS and 2) whether directly inducing autophagy could decrease cell death and improve outcome. Here we show that administering an ALK5 antagonist 3 days after HI reduced actively apoptotic cells by ~90% when assessed one week after injury. Ex vivo studies using the lysosomal inhibitor chloroquine confirmed that SB505124 enhanced autophagy flux in the injured hemisphere, with a significant accumulation of the autophagic proteins LC3 and p62 in SB505124 + chloroquine treated brain slices. We independently activated autophagy using the stimulatory peptide Tat-Beclin1 to determine if enhanced autophagy is directly responsible for improved outcomes. Administering Tat-Beclin1 starting 3 days after injury preserved the structural integrity of the hippocampus and thalamus with improved sensorimotor function. These data support the conclusion that intervening at this phase of injury represents a window of opportunity where stimulating autophagy is beneficial.
RS2: Assessing Conversion to Transdermal Fentanyl or Methadone during Transition on Hospice Admission

Background: Transdermal fentanyl (TDF) or oral methadone are often select as effective options for patients transitioning to hospice. Compared to other opioid options (e.g. oxycodone, morphine, hyd...
Optimal Policy in Single-Server Multi-Class Queuing Systems with Abandonment

We study a multi-class queuing system with a single server and customer abandonment. We fully characterize the structure of the server's optimal scheduling policy that minimizes the long-run average customer abandonment cost. We show that the optimal service policy is a static priority policy. We derive sufficient conditions under which the so-called b.mu-rule is optimal. Under the b.mu-rule, it is optimal to give priority to the customer type that has higher service rate (mu) and higher abandonment cost (b), i.e., higher index b.mu.
Comparison of Diversion Strategies for Management of Acute Complicated Diverticulitis in a US Nationwide Cohort.

Importance Diverticulitis of the colon is an increasingly prevalent disease with significant implications for patient quality of life and health system resource expenditure. Although several randomized clinical trials and meta-analyses of Hartman procedure (HP) and primary anastomosis and proximal diversion (PAPD) have found surgical equipoise, questions regarding the relative performance of these treatments when applied broadly remain. Objective To examine use of and outcomes after urgent sigmoid colectomy with end colostomy (ie, HP) vs PAPD in management of complicated diverticulitis. Design, Setting, and Participants This retrospective cross-sectional study was a multicenter, population-based examination of inpatient hospitalizations, not including long-term rehabilitation facilities, using data from the 2014 to 2017 Nationwide Readmissions Database. It was performed from November 2020 to January 2021. Included patients were adults admitted with acute diverticulitis requiring HP or PAPD within 48 hours of admission. Exposures Undergoing HP vs PAPD. Main Outcomes and Measures Inverse probability treatment analysis was used to compare outcomes, including index mortality, composite complications (ie, neurologic, infectious, and cardiovascular complications), length of stay, and readmissions within 90 days. Results During the study period, an estimated 1 072 395 adults (615 954 [57.4%] women; median [IQR] age, 64 [52-76] years) required nonelective hospitalization for acute colonic diverticulutus. A total of 34 126 patients required diversion, with 32 326 patients (94.7%) undergoing HP and 1800 patients (5.3%) undergoing PAPD within 48 hours of admission. Patients undergoing PAPD had a decreased median (IQR) age (60 [51-70] years vs 65 [54-74] years; P < .001) and decreased rates of end organ dysfunction (520 patients [28.9%] vs 11 514 patients [35.6%]; P < .001). In inverse probability treatment weight analysis, the odds of mortality (adjusted odds ratio [aOR], 0.63; 95% CI, 0.32-1.40), complications (aOR, 0.86; 95% CI, 0.66-1.13), and nonhome discharge (aOR 1.15; 95% CI, 0.83-1.60) were similar for PAPD compared with HP. Among 1772 patients who underwent PAPD and survived index hospitalization, there was an increased incidence of 90-day readmission compared with 30 851 patients who underwent HP and survived index hospitalization (393 patients [22.2%] vs 4384 patients [14.2%]; P < .001) with increased hazard of ostomy reversal (hazard ratio, 1.46; 95% CI, 1.08-1.99). Conclusions and Relevance This study found that the use of PAPD was associated with comparable index hospitalization outcomes vs use of HP, while readmission rate and ostomy risk were statistically significantly increased among patients who underwent PAPD compared with patients who underwent HP. These findings suggest that further delineation of criteria for appropriate application of PAPD in the urgent setting are warranted.
The costs of bankruptcy

Abstract Bankruptcy-related costs may be categorized into four areas: (1) Real costs borne by the distressed firm; (2) Real costs borne directly by the claimants; (3) Losses to the distressed firm that are offset by gains to other entities; (4) Real costs borne by parties other than the distressed firm or its claimants. Cost categories 1, 2, and 3 are relevant for claimants, while Categories 1, 2, and 4 are relevant for society. Focusing on the first three categories, the present study reaches the following conclusions: First, after allowing for their costs of collections, claimsholders recover approximately 56% of the bankrupt firm's predistress value (PDV). Second, dealing with financial distress generally consumes between 12% and 20% of the distressed firm's PDV. Taking the midpoint of this range (16%) implies that the losses that lead to the firm's distress average approximately 28% of its PDV. These estimated values demonstrate the importance of bankruptcy costs in determining an optimal capital structure and explaining the level of risk premiums. Because of its impact on risk premiums, the cost of capital and needed tax rates, the cost of dealing with financial distress has an adverse impact on resource allocations throughout the economy.
Mouse cytochrome P-450EF, representative of a new 1B subfamily of cytochrome P-450s : cloning, sequence determination and tissue expression

Abstract A novel benz[a]anthracene and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-inducible cytochrome P-450 (P450EF), which is very active in polycyclic aromatic hydrocarbon metabolism, has been purified from C3H10T1/2 mouse embryo fibroblasts (Pottenger, L. H., Christou, M., and Jefcoate, C. R. (1991) Arch. Biochem. Biophys. 286, 488-497). P450EF was shown to be immunologically unrelated to the major known P-450 families. A 4.9-kilobase (kb) cDNA encoding P450EF has been isolated from a lambda ZAP cDNA expression library generated from mRNA of TCDD-induced C3H10T1/2 cells. This cDNA comprises 175-base pair (bp) 5'-noncoding, 1629-bp open reading, and about 3100-bp 3'-noncoding sequence. A SmaI fragment of the 4.9-kb cDNA hybridized to a 5.2-kb mRNA species equally induced by benz[a]anthracene (10 microM) and TCDD (10 nM) in C3H10T1/2 cells, consistent with the involvement of the Ah receptor in this induction process. The deduced amino acid sequence (543 amino acids), the longest of any known cytochrome P-450, exhibits 41 and 38% identity to mouse CYP1A1 and CYP1A2, respectively, and less but substantial similarity (30-33% identity) to many members of the CYP2 family. There are five extended regions of > or = 50% identity to CYP1A1 as follows: (a) 51-118; (b) 199-222; (c) 326-343 (I-helix, O2-binding threonine); (d) 357-430; and (e) 460-487 (heme-binding cysteine). These sequence relationships suggest that P450EF is a member of a new CYP1B subfamily (mouse CYP1B1). Hybridization of mRNA and immunoblot analyses of microsomes both demonstrated beta-naphthoflavone (beta-NF) inducibility of Cyp1b-1 expression in C3H mouse lung, liver, and uterus although at lower levels relative to Cyp1a-1. The mobility of the beta-NF-inducible immunoreactive liver protein was significantly higher than that of the CYP1B1 protein detected in mouse lung, uterus, and C3H10T1/2 cells. Compared with the beta-NF-induced uterus, polycyclic aromatic hydrocarbon-induced uterine fibroblasts exhibited 10-20-fold higher levels of CYP1B1, suggesting that stromal fibroblasts are a major source of the protein.
Hormonal regulation of glycogen synthase: Insulin decreases protein kinase sensitivity to cyclic AMP

Rat hemidiaphragms incubated with epinephrine exhibited increases in cyclic AMP content and protein kinase activity which were proportional to the logarithm of the hormone concentration from 0.1--2 microM. The fraction of glycogen synthase made independent of glucose-6-P for activity (%I) decreased concomitantly, but correlated only with epinephrine concentrations up to 0.2 microM. Insulin (0--100 mU/ml) increased glycogen synthase %I in a dose-dependent manner with no change in cyclic AMP concentration. Protein kinase activity increased slightly at the lowest insulin concentration, then decreased slightly as glycogen synthase %I increased. Insulin was without effect when administered with a supramaximal dose of epinephrine. In the presence of submaximal epinephrine, insulin produced a dose-dependent increase in glycogen synthase %I which correlated with a decrease in protein kinase activity, without changing cyclic AMP. Insulin had no effect on the increases in cyclic AMP produced by varying levels of epinephrine. However, the activation of protein kinase activity by endogenous cyclic AMP was inhibited in the presence of insulin. The glycogen synthase %I response to epinephrine also was less sensitive in the presence of insulin. Insulin antagonizes the activation of cyclic AMP-dependent protein kinase by epinephrine without altering cyclic AMP levels.
Abstract 18516: Regional Dysfunction of Left Atrial Appendage and its Association with Stroke in Atrial Fibrillation

Background: Atrial Fibrillation (AF) is associated with an increased risk of cardioembolic stroke. Previous studies demonstrate that the Left atrial appendage (LAA) is the most common site of intracardiac thrombus, and the LAA morphology alone may determine the risk of stroke. We aimed to determine the association between LAA regional dysfunction using novel, noninvasive, image-based motion-estimation CT (iME) and prior history of stroke in patients with AF. Methods: Among the patients with history of AF referred for ablation who underwent pre-ablation CT with retrospective ECG gating, we identified 18 patients with a prior history of stroke or TIA, and 18 age- and gender-matched controls. The patients in AF at the time of CT were excluded. Four-dimensional motion vector field was estimated from reconstructed CT images using iME at every 5% RR interval. To assess myocardial deformation, area change ratio and area change rate were calculated over the endocardial surface of the LA and LAA. Univariate and multivariate comparisons were made by using binary logistic regression model. Results: A total of 36 patients (mean age 67.6 ± 8.1 years, 66.7% male, 16.7% persistent AF) were included in the study. Univariate analysis showed that the LA pre-atrial contraction area change ratio and LAA maximum area change ratio were significantly lower (P= 0.02 and 0.04, respectively) in the stroke/TIA group compared to the control group. These changes remained statistically significant in multivariate analysis (P=0.03 and 0.04, respectively) after adjusting for age, sex, body mass index, LV ejection fraction, type of AF, and CHADS score. Conclusions: LAA regional dysfunction is associated with stroke/TIA in patients with AF. LAA regional dysfunction detected by iME could represent a marker for stroke and a possible therapeutic target.
Cognate CD40-CD40L interaction is important for maintenance of thymic B cells. (IRM8P.705)

B cells are present in the thymus in numbers similar to dendritic cells and epithelial cells, but the functional roles of thymic B cells and the mechanisms that support this population are unclear. Previously, we showed B cells are essential for endogenous superantigen-mediated thymocyte negative selection. In this study, we investigated mechanisms regulating thymic B cells. Thymic B cell frequency and absolute number are markedly lower in TCRa KO mice, indicating the necessity of SP-T cells for maintenance of thymic B cells. Thymic B cell numbers are also reduced in mice expressing a TCR Tg in absence of antigenic ligand, but dramatically increased in mice expressing both TCR and corresponding ligand, demonstrating TCR recognition and thymocyte activation strongly influence thymic B cells. To elucidate molecular interactions that underlie the requirement for activated T cells, we tested the role of CD40L expressed on activated SP-T cells interacting with CD40 to mediate thymic B cell maintenance. In CD40L and CD40 KO, thymic B cell frequency is substantially reduced. In mixed BM-chimeras in which CD40 KO and WT donor-derived cells co-exist, cell autonomous CD40 expression is important for thymic B cell maintenance, whereas mixed BM-chimeras using MHCII KO and WT showed that cell autonomous MHCII expression plays no detectable role. Thus, CD40L-CD40 cognate interaction, but not MHCII-TCR cognate interaction, between T cells and B cells supports the thymic B cell population.
A beamline design and data acquisition with the 20-MeV, 20-ps electron beam for the higher-order mode studies of the APS SR-RF cavities

A beamline has been designed and assembled to use the ANL Chemistry Division 20-MeV electron linac for the testing of higher-order mode excitation and damping in RF cavities. The beamline consists of two sections (a beam collimating section with a 1.5"-OD vacuum line, and a cavity test section with a 3"-OD vacuum line), separated by two double aluminum foil windows. The beam diagnostics consist of a stripline beam position monitor, integrating current transformers, fluorescent screens, and a Faraday cup. EPICS (Experimental Physics and Industrial Control System) is used for beamline control, monitoring and data acquisition. Also described is the diagnostic system used for beam image capture and analysis using EPICS-controlled hardware and PV-WAVE software. The RF cavity measurement will be described in a separate paper. >