cssi/SciSciGPT-SciSciNet huggingface dataset:
The effect of timing and graft dysfunction on survival and cardiac allograft vasculopathy in antibody-mediated rejection.

Background Antibody-mediated rejection (AMR) has been associated with increased death and cardiac allograft vasculopathy (CAV). Early studies suggested that late AMR was rarely associated with graft dysfunction, whereas recent reports have demonstrated an association with increased mortality. We investigated the timing of AMR and its association with graft dysfunction, death, and CAV. Methods This retrospective cohort study identified all adult orthotopic heart transplant (OHT) recipients ( N = 689) at Columbia University Medical Center from 2004 to 2013. There were 68 primary cases of AMR, which were stratified by early ( 1 year post-OHT) AMR. Kaplan-Meier survival analysis and modeling was performed with multivariable logistic regression and Cox proportional hazards regression. Results From January 1, 2004, through October 1, 2015, early AMR (median 23 days post-OHT) occurred in 43 patients and late AMR (median 1,084 days post-OHT) occurred in 25. Graft dysfunction was less common with early compared with late AMR (25.6% vs 56%, p = 0.01). Patients with late AMR had decreased post-AMR survival compared with early AMR (1 year: 80% vs 93%, 5 years: 51% vs 73%, p p p = 0.009), whereas all other groups were all similar to the general transplant population. Conclusions Late AMR is frequently associated with graft dysfunction. When graft dysfunction is present in late AMR, there is an early and sustained increased risk of death and rapid development of de novo CAV despite aggressive treatment.
Health Survey on Star-Rated Hotel Rooms of Olympic Authorized

[Objective] To understand the problems of health status of rooms among different types of Olympic authorized star-rated hotels,and guide operators to take improved measures.[Methods] Sanitary quality of rooms in 45 Olympic authorized hotels were sampled and tested in Chaoyang District of Beijing during June to August in 2007.[Results] Most qualified rates of indicators are more than 90%,that of formaldehyde,respirable particulate matter and total number of bacteria in the air was lower,with 88.1%、75.5%、86.8% respectively.Qualified rate of public appliances disinfection efficacy monitoring was higher.Indicators of formaldehyde,respirable particulate matter,relative humidity,noise detection between different star-rated hotels was significant.(χ2=9.487,P=0.009;χ2=52.600,P=0.000;χ2=8.164,P=0.017;χ2=6.097,P=0.047)[Conclusion] Sanitation quality of Olympic authorized hotels rooms is high,but it should be raised further to ensure public health in good status during the Olympic Games.
On Oil－Gas Migration Systems and Their Control over the Formation of Reservoir．

 Through the analysis of migration systems in subground rocks this paper indicates that the oil－gas migration system is consisted of three main element i．e． the pore fracture and the pore－fracture combination． This paper puts forward the simple migration system consisting of connecting sand body fault and unconformity surface as well as the compound migration system consisting of sand body－unconformity surface sand body－fault unconformity surface－fault or sand body－unconformity surface－fault and both kinds of subground migration systems provide a three diamentional channel network for oil－gas migration． The type of oil－gas migration systems control the forming pattern of oil－gas reservoir． Connecting sand body migration systems may controls the forming of oil－gas reservoir due to bottom bed overlap lithologic pinch out and／or the fault hairier． The migration system consisting of unconformity surface sand body－unconformity surface and／or unconformity surface－fault may control the forming of the bedrock weathered crust type oil－gas reservoir． The migration system consists of fault sand body－fault and／or sand body－unconformity surface may control formation of oil－gas reservoir due to fault block anticline structure－lithologic and／or fault－lithology．
Petal Tool for Analyzing and Transforming Legacy MPI Applications

Legacy MPI applications are an important and economically valuable category of parallel software that rely on the MPI-1, MPI-2 and, more recently, MPI-3 standards to achieve performance and portability. Many of these applications have been developed or ported to MPI over the past two decades, with the implicit dual goal of achieving acceptably high performance and scalability, and a high level of portability between diverse parallel architectures. However they were often created implicitly using MPI in ways that exploited how a particular underlying MPI behaved at the time such as those with polling progress and poor implementation of some operations. Thus, they did not necessarily take advantage of the full potential for describing latent concurrency or for loosening the coupling of the application thread from the message scheduling and transfer. This paper presents a first transformation tool, Petal, that identifies calls to legacy MPI primitives. Petal is implemented on top of the ROSE source-to-source infrastructure and automates the analysis and transformation of existing codes to utilize non-blocking MPI and persistent MPI primitives. We use control flow and pointer alias analysis to overlap communication and computation. The transformed code is capable of supporting better application bypass, yielding better overlapping of communication, computation, and I/O. We present the design of the tool and its evaluation on available benchmarks.
Influence of varying levels of blood progesterone upon estrous behavior in cattle.

The effect of four levels of progesterone on the occurrence and intensity of estrous behavior was determined in ovariectomized cows. Twelve Holsteins were bilaterally ovariectomized at least 2 mo before treatment. Progesterone (P4) was administered im two times/day for 5 d followed 72 h later with 2 mg estradiol (E2) im to induce estrous behavior. Treatments were control = oil, 100 mg P4/d, 300 mg P4/d and 500 mg P4/d. Each animal received all P4 treatments in a 4 X 4 Latin-square design. From d 2 through 6, with d 1 being the first day of P4 treatment, serum P4 concentrations averaged .3, 2.5, 6.1 and 12.3 ng/ml in treatments I to IV, respectively. Progesterone levels at the time of peak E2 (d9) were less than 1 ng/ml for treatments I, II and III and 1.8 ng/ml for treatment IV. Peak E2 levels for all groups averaged 23.9 pg/ml (12 h after E2 injection). Cows were observed continuously for 48 h after E2 injection to quantitate estrous behavior. Behavioral traits measured were: mounts initiated, mounts received, standing when mounted, chin rests initiated and chin rests received. Progesterone treatment caused a decrease in frequency of all five traits measured. As P4 levels increased, there was a linear (P less than .01) decrease in frequency of a behavioral trait. The percentage of the cows that showed each behavioral trait and mean time to first occurrence of each trait were not different after progesterone treatment, with the exception of standing behavior.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of Wastewater Disinfection on Human Health

Wastewater disinfection is practiced with the goal of reducing risks of human exposure to pathogenic microorganisms. Ideally, this goal is to be met without introducing other risks, such as those that could be associated with disinfection by-products. The purpose of this research was to assess the effects of wastewater disinfection on human health. Fecal coliforms and enterococci were both critically examined in terms of their ability to function as indicator organisms. Both bacterial groups were observed to be easily inactivated by chlorine and UV, and both indicators were observed to be relatively sensitive to these disinfectants, as compared with the remaining bacterial population. These observations are even more important when it is recognized that these indicator species represent a small fraction of the total bacterial population in wastewater effluent samples. Total culturable bacteria (TCB) were suggested as a possible alternative to coliform bacteria and enterococci as bacterial indicators. TCB represents a larger fraction of the bacterial population. However, the TCB assay requires a longer incubation time than is required for either coliforms or enterococci, and provides essentially no specificity in the analysis of water samples. Taken together, and when considered in conjunction with previously published research, the results of these experiments illustrate several important limitations of common disinfection processes as applied in the treatment of municipal wastewaters. In general, it is not clear that disinfection processes, as commonly implemented, are effective for control of the risks of disease transmission, particularly as associated with viral pathogens. Microbial and chemical quality in receiving streams may not be substantially improved by the application of these methods; under some circumstances, it could be argued that disinfection may actually yield a decrease in effluent and receiving water quality. Decisions regarding the need for effluent disinfection must account for site-specific characteristics, but it is not clear that disinfection of municipal wastewater effluents is necessary or beneficial for all facilities. When direct human contact or ingestion of municipal wastewater effluents is likely (i.e., close to an outfall or in cases of discharge to bathing areas or food production areas), disinfection appears to be necessary. Under these circumstances, the data from these experiments illustrate clear advantages of UV irradiation over chlorination in terms of microbial quality, as well as chemistry and toxicology. This advantage is more evident in effluents that contain appreciable quantities of ammonia-N or organic-N. This title belongs to WERF Research Report Series ISBN: 9781843396734 (Print) ISBN: 9781780403274 (eBook)
The Max-Pressure Controller for Arbitrary Networks of Signalized Intersections

The control of an arbitrary network of signalized intersections is considered. At the beginning of each cycle, a controller selects the duration of every stage at each intersection as a function of all queues in the network. A stage is a set of permissible (non-conflicting) phases along which vehicles may move at pre-specified saturation rates. Demand is modeled by vehicles entering the network at a constant average rate with an arbitrary burst size and moving with pre-specified average turn ratios. The movement of vehicles is modeled as a “store and forward” queuing network. A controller is said to stabilize a demand if all queues remain bounded. The max-pressure controller is introduced. It differs from other network controllers analyzed in the literature in three respects. First, max-pressure requires only local information: the stage durations selected at any intersection depends only on queues adjacent to that intersection. Second, max-pressure is provably stable: it stabilizes a demand whenever there exists any stabilizing controller. Third, max-pressure requires no knowledge of the demand, although it needs turn ratios. The analysis is conducted within the framework of “network calculus,” which, for fixed-time controllers, gives guaranteed bounds on queue size, delay, and queue clearance times.
The Name of the Game Is Money — But the Disputes Are about Where the Jobs Are

International finance is a game with two sets of players: one set includes the politicians and bureaucrats and the central bankers in different countries and the other set includes the chief financial officers and treasurers of giant, large, medium-large, medium, medium-small, and small firms and banks and hedge funds, and other financial institutions. The government officials want to win elections and secure a niche in the histories of their countries for enhancing economic well-being and financial stability. The cliche is ‘good jobs at good wages.’ A few aspire to get their portraits on the national currency. And to do so, they want to manage their economies to provide more and better-paying jobs and greater financial security for their voters. These officials want to avoid sharp increases in inflation rates and sharp declines in the prices of their currencies.
Scientific intuitions about the mind are wrong, misled by consciousness.

Logic is a fundamental reason why computational accounts of the mind have failed. Combinatorial complexity preventing computational accounts is equivalent to the Godelian incompleteness of logic. The mind is not logical, but only logical states and processes in the mind are accessible to subjective consciousness. For this reason, intuitions of psychologists, cognitive scientists, and mathematicians modeling the mind are biased toward logic. This is also true about the changes proposed in After Phrenology (Anderson 2014).
Tourette Syndrome with Gyrus Rectus Cysts

Multicystic changes in the gyrus rectus of the left frontal lobe were demonstrated by brain magnetic resonance imaging in an 11-year-old boy with Tourette syndrome reported from Children’s Regional Hospital at Cooper Hospital/University Medical Center, Camden, NJ.
Estimation of Heat Transfer Coefficients for Biomass Particles by Direct Numerical Simulation Using Microstructured Particle Models in the Laminar Regime

Direct numerical simulation of convective heat transfer from hot gas to isolated biomass particle models with realistic morphology and explicit microstructure was performed over a range of conditions in the laminar regime. Steady-state results demonstrated that convective interfacial heat transfer is dependent on the wood species. The computed heat transfer coefficients were shown to vary between the pine and aspen models by nearly 20%. These differences are attributed to the species-specific variations in the exterior surface morphology of the biomass particles. We also quantify variations in heat transfer experienced by the particle when positioned in different orientations with respect to the direction of fluid flow. These results are compared to previously reported heat transfer coefficient correlations in the range of 0.1 < Pr < 1.5 and 10 < Re < 500. Comparison of these simulation results to correlations commonly used in the literature (Gunn, Ranz–Marshall, and Bird–Stewart–Lightfoot) shows that the...
Heteronormativity made me lesbian: Femme, butch and the production of sexual embodiment projects:

Queer theory argues that ruling heteronormative discourses are productive of sexualities. How then does heteronormativity produce lesbians? We theorize femme and butch as sexual embodiment projects...
Individualism-Collectivism and Reaction to Diversity

With the acceleration of globalization and diversification of the workforce in contemporary organizations, managing diversity to realize much potential benefits in diverse work groups has become mo...
Wet-Site Excavation and Field Methodology at Butrint, Albania: The Roman Forum Excavations Project

ABSTRACTSince the start of archaeological research at the UNESCO World Heritage Site of Butrint (Bouthrotos/ Buthrotum) in southern Albania, archaeologists have allowed the water table to serve as a limit to archaeological excavation. From 2011 to 2013, the Roman Forum Excavations (RFE) Project conducted the first wet-site excavations at Butrint, reaching depths of up to 4 m below the water table in the ancient urban center. Well-preserved wood and other organic remains were recovered from waterlogged deposits, dating as early as the 7th century b.c. Major changes in RFE Project methodology emerged in response to wet-site archaeology. Unskilled local workers were trained to become local excavators. This significantly improved excavation techniques and recording procedures and enhanced the quality of the archaeological data, showing the high degree to which seemingly disparate elements of field methodology are intertwined.
Mercury Safety Reform in the 21st Century: Advancing the New Framework for Toxic Substances Control

The articles that follow are the latest in Environment Magazine's series looking back at seminal articles in the magazine's history that helped define a field of study or offered alternative explorations of new ideas. In this installment, we focus on the latest news in the hazards of the mercury toxin, juxtaposed with Environment's groundbreaking article on mercury published in 1969.
Impact of Noninvasive Follicular Thyroid Neoplasm With Papillary-Like Features on Adequacy Criteria and Risk of Malignancy of Thyroid Fine-Needle Aspiration.

Objectives The impact of noninvasive follicular thyroid neoplasm with papillary-like features (NIFTP) on nondiagnostic and benign diagnoses is not well characterized. Methods The results of all thyroid fine-needle aspirates (FNAs) performed from 1997 to June 2016 with corresponding resections were reviewed. Results From 12,764 aspirates, there were 8,106 (64%) benign diagnoses with 412 (5%) resections and 1,888 (14.8%) nondiagnostic diagnoses with 329 (17%) resections. Before the use of NIFTP, there were 18 (4.3%) malignancies in the benign aspirates and 39 (11.9%) malignancies in the nondiagnostic aspirates. There were 12 NIFTP cases on review. After reclassification using NIFTP, there were 10 of 412 (2.4%) malignancies in the benign aspirates. When cases with 10 to 60 benign follicle cells without atypia or Hurthle cell change were reclassified as benign rather than nondiagnostic, the malignancy rate for a benign aspirate decreased (12/506, 2.3%; P = 1.0) when NIFTP cases were recognized. Conclusions With NIFTP, reducing the threshold for adequacy from 60 to 10 cells led to nonsignificant decrease in the risk of malignancy of a benign diagnosis (2.4% to 2.3%). Thyroid fine-needle aspirates with 10 to 60 benign cells without atypia or Hurthle cell change should be diagnosed as benign.
Commentary on “Effectiveness of Treatment Modalities on Kidney Stone Recurrence”

In this evidence-based nephrology review, Zisman ([1][1]) comprehensively summarizes the evidence regarding dietary and pharmacologic interventions for the prevention of kidney stone recurrence. As the author notes, the preponderance of this evidence relates to prevention of calcium oxalate stone
Salivary intercellular adenosine triphosphate testing in primary caretakers: An examination of statistical significance versus diagnostic predictability

A primary caretaker is a potential reservoir of bacteria for an infant child and can be evaluated during a child's caries risk assessment. The aim of this study was to investigate an indirect method for assessing Streptococcus mutans and Streptococcus sobrinus (MS) and lactobacillus (LB) levels in a caretaker's saliva. Thirty-eight primary caretakers participated in the study to determine whether a 2-step method to assess the intracellular adenosine triphosphate (ATP) levels in saliva (saliva i-ATP method) predicted higher MS and LB levels. This method was tested against a 1-step swab-based total ATP testing of dental plaque (plaque t-ATP method). Receiver operating characteristic (ROC) curves were used to examine the relationship between specificity and sensitivity of the two diagnostic tests. Although the area under the ROC curves of both the saliva i-APT (0.823) and the plaque t-ATP (0.774) methods were shown to be statistically different (p < .05) than the null hypothesis test of a random coin flip, the diagnostic predictability of the ATP tests to assess high levels of MS and LB remained low. The optimal cutoff, which was defined by the Youden index, for the saliva i-ATP method produced a sensitivity/specificity of 60.7/100.0 for MS and 78.6/88.9 for LB. Applying these results to populations of low or high bacterial level prevalence produced undesirable positive and negative predictive values for future potential patients. A pair-wise comparison of both area under the ROC curve values of the saliva i-ATP and plaque t-ATP did not find a statistically significant difference in using one test over the other (MS, p = .629; LB, p = .737). The findings of this study can educate dental clinicians that diagnostic tests, such as the 2-step saliva i-ATP method, can be found to be statistically significant but not ideal for patient use in terms of diagnostic predictability.
Acute Myeloid Leukemias with Recurrent Cytogenetic Abnormalities

Acute leukemias are clonal malignant disorders resulting from genetic alterations in hematopoietic stem cells that limit the ability of stem cells to differentiate into red cells, granulocytes, and platelets, and lead to the proliferation of abnormal leukemic cells or “blasts.” Acute myeloid leukemias (AML), also referred to as acute nonlymphocytic leukemias, are heterogeneous disorders. The current World Health Organization (WHO) classification scheme of acute myeloid leukemia and myelodysplastic syndrome (MDS) has evolved away from the French–American–British (FAB) classification scheme, which only uses morphologic features for classifying those neoplasms. The current WHO classification scheme includes not only morphologic features, but also clinical, immunophenotypic, and cytogenetic features. The current 2008 WHO classification includes four main categories of AML: AML with recurrent genetic abnormalities, AML with myelodysplasia-related changes, therapy-related myeloid neoplasms, and AML not otherwise specified (Table 34.1). The pathogenesis and underlying molecular processes substantially differ between each of these AML groups: AMLs with recurrent cytogenetic abnormalities are discussed in this chapter after a general introduction to the topic. However, AMLs with mutated NPM1 and AMLs with mutated CEBPA will be discussed in Chap. 35, as will AMLs with normal cytogenetics. AMLs with myelodysplasia-related changes and therapy-related AMLs are discussed in Chap. 36.
Cancer of the Periauricular Region

Although carcinomas of the auricular and periauricular regions can be diagnosed early and often can be cured, many of these tumors become difficult to treat because of local spread and regional metastasis. Those tumors that are not treated early often require more aggressive treatment. Mohs histographic surgery combined with conventional excision affords the best marginal control for local eradication of these tumors.
Mechanisms for efficiency in blackboard systems

The RETE algorithm had a great impact on the development of efficient production systems by providing a fast pattern matching mechanism for activation. No similar mechanism has been available to speed up activation and scheduling in blackboard systems. In this paper we describe efficient, general-purpose efficiency mechanisms that are better suited to blackboard systems than RETE-like networks. We describe a knowledge source compiler that produces match networks and demons for efficient activation and rating while compiling the entire system for increased execution speed. Experiments using the enhancements in a general-purpose blackboard shell illustrate a substantial improvement in run time, including an 80-92% decrease in activation time. The mechanisms we describe are general enough to be used in most existing blackboard systems.
Evaluation of WebxPST: a browser-based authoring tool for problem-specific tutors

Authoring tools enable the more rapid creation of intelligent tutoring systems. Such tools are essential for tutors to become more widespread. In this study we evaluate WebxPST, a browser-based authoring system that enables non-programmers to create model-tracing-like intelligent tutors. Five authors, two course instructors and three undergraduates, created 74 problems suitable for use in an undergraduate statistics curriculum. A subset of these problems was deployed in a classroom. These authors quickly mastered the authoring interface showing the feasibility of the tool.
Uncertainties in soil physicochemical factors controlling phosphorus mineralization and immobilization processes

Abstract It became increasingly important to regulate phosphorus (P) loss from P-rich agricultural fields because of accelerated eutrophication and hypoxia in freshwater and coastal marine systems in the world. Understanding the P stabilization mechanisms in soils, such as mineralization and immobilization, will help in adopting good agricultural management practices and implementing watershed-scale monitoring programs. This review examined the current knowledge of P mineralization and immobilization in soils and physicochemical factors that are influencing the terrestrial P cycle. It has been our common knowledge that a ratio of C:P in organic residue controls the fate of P in soils. Accepted thresholds for mineralization and immobilization are approximately 200:1 and 300:1, respectively. However, it was found that various abiotic and biotic factors influence the P mineralization and immobilization in soils. In this chapter, we reviewed P mineralization/immobilization studies that examined the impact of microbial C:P ratio, pH, labile organic and inorganic P, aeration, moisture content, types of organic C and N, microbial biomass, vegetation type, and microbial- and plant-driven phosphatase activity, and intensity of anthropogenic management. In summary, we presented uncertainties from conflicting results that require further examination.
Representing uncertainty in natural hazard risk assessment with Dempster Shafer (Evidence) theory

Mathematical frameworks are developed to address the representation of inherent uncertainties in the assessment of natural hazard risk for the built environment. Lack of exploration of such theorie...
Methane adsorption capacity of shale samples from Western Australia

AbstractTo examine the influence of clay minerals on methane adsorption in shales, shale samples with low total organic carbon (TOC), ranging from 0.23 to 3.2 wt%, were collected from the Canning a...
Atrial Fibrillation and Stroke: The View from Neurology

Atrial fibrillation is the most frequent cardiac disorder associated with ischemic stroke. Most, but certainly not all strokes in patients with atrial fibrillation, are due to an embolus dislodged from a left atrial thrombus. A large number of these patients also have cerebrovascular disease that may be responsible for their stroke. Thus the diagnostic dilemma in these patients is to determine which potential stroke mechanism is in fact responsible for their stroke. Once the mechanism is determined a course of rational, if not scientifically proven, therapy can be instituted. What follows is a summary of our current criteria for the diagnosis of cardiogenic brain embolism, observations on the nature of stroke in patients with nonvalvular atrial fibrillation (NVAF), and some recommendations regarding the anticoagulant management of these patients.
Effects of ecgonine methyl ester on cognition in scopolamine-impaired and aged rats.

Searches for antidotes to cocaine, and for cognition enhancers potentially applicable to Alzheimer’s disease, have revealed a novel regulatory site on nicotinic acetylcholine receptors. In the presence of an agonist, inhibitors binding to this site changed the ion channel equilibrium from the open-channel form towards the closed form. Other, related, molecules could bind to the site without changing the equilibrium. These latter compounds were predicted to displace the inhibitors without affecting receptor function per se. These compounds alleviated the inhibition. One of them is ecgonine methyl ester (EME), which is generally described as inactive, but this work suggested a beneficial effect on cognition. This in vivo study tested for cognitive enhancement by EME in scopolamine-impaired, and aged, rats. Memory was the primary endpoint, but thigmotaxis became an important secondary endpoint in the light of observations made during the study. Impaired cognition was pharmacologically induced by scopolamine in young rats, and spontaneously present in aged rats. Learning ability before and after administration of EME was tested in Morris water maze protocols. Concentrations of EME in the brain and plasma were analyzed by gas chromatography-mass spectrometry. A single dose of EME reversed scopolamine impairment, indicating involvement of acetylcholine receptors. Longer-term treatment improved cognition in aged rats, with enhanced rates of learning in the absence of an exogenous cognition-impairing compound. Impairment returned with a new challenge; the improvement could be re-established with continued dosing. EME also reversed thigmotaxis seen in aged rats; thigmotaxis is believed to indicate anxiety. The concentrations of EME in the brain proved adequate drug exposure. Since other investigators have shown cognition impairment caused by cocaine in aged rats, this work shows that cocaine and EME have opposite effects in Morris water maze models. EME might induce cognitive enhancement and relief of anxiety in cocaine-impaired humans, and in other cognitive disorders.
Spatial Structured Prediction Models: Applications, Challenges, and Techniques

Spatial structure patterns are prevalent in many real-world data and applications. For example, in biochemistry, the geometric topology of a molecular surface indicates protein functions; in hydrology, irregular geographic terrains and topography on the Earth’s surface control water flows and distributions; in civil engineering, wetland parcels in remote sensing imagery are often made up of contiguous patches. Spatial structured prediction aims to learn a prediction model whose input and output data contain a spatial structure. Modeling spatial structural information in prediction models is critical for interdisciplinary applications due to two reasons. First, explicit spatial structural information often indicates the underlying physical process, and thus enhances model interpretability. Second, spatial structural constraints also have positive side-effects of enhancing model robustness against noise and obstacles and regularizing model learning when training labels are limited. However, spatial structured prediction also poses several unique challenges, such as the existence of implicit spatial structure in continuous space, structural complexity in geometric topology, and high computational costs. Over the years, various techniques have been proposed for spatial structured prediction in different applications. This paper aims to provide an overview of the spatial structured prediction problem. We provide a taxonomy of techniques based on the underlying approaches. We also discuss several future research directions. The paper can potentially not only help interdisciplinary researchers find relevant techniques but also help machine learning researchers identify new research opportunities.
Nutraceutical and pharmaceutical cocktails did not preserve diaphragm muscle function or reduce muscle damage in D2-mdx mice.

NEW FINDINGS What is the central question of this study? We previously demonstrated that quercetin transiently preserved respiratory function in dystrophin-deficient mice. To gain lasting therapeutic benefits, we tested quercetin in combination with nicotinamide riboside, lisinopril and prednisolone in the D2-mdx model. What is the main finding and its importance? We demonstrated that these quercetin-based cocktails did not preserve respiratory or diaphragmatic function or reduce histological damage after 7 months of treatment starting at 4 months of age. ABSTRACT Duchenne muscular dystrophy is characterized by the absence of dystrophin protein and causes muscle weakness and muscle injury, culminating in respiratory failure and cardiomyopathy. Quercetin transiently improved respiratory function but failed to maintain long-term therapeutic benefits in mdx mice. In this study, we combined quercetin with nicotinamide riboside (NR), lisinopril and prednisolone to assess the efficacy of quercetin-based cocktails. We hypothesized that quercetin, NR and lisinopril independently would improve respiratory function and decrease diaphragmatic injury and when combined would have additive effects. To address this hypothesis, in vivo respiratory function, in vitro diaphragmatic function and histological injury were assessed in DBA (healthy), D2-mdx (dystrophic) and D2-mdx mice treated with combinations of quercetin, NR and lisinopril from 4 to 11 months of age. Respiratory function, assessed using whole-body plethysmography, was largely similar between healthy and dystrophin-deficient mice. Diaphragm specific tension was decreased by ∼50% in dystrophic mice compared with healthy mice (P < 0.05), but fatigue resistance was similar between groups. Contractile area was decreased by ∼10% (P < 0.05) and fibrotic area increased from 3.5% in healthy diaphragms to 27% (P < 0.05) in dystrophic diaphragms. Contrary to expectations, these functional and histological parameters of disease were not offset by any intervention. These data suggest that quercetin, NR and lisinopril, independently and in combination, did not prevent diaphragmatic injury or preserve respiratory function.
Despite early Medicaid expansion, decreased durable virologic suppression among publicly insured people with HIV in Washington, DC: a retrospective analysis

Despite widely available access to HIV care in Washington, DC, inequities in HIV outcomes persist. We hypothesized that laboratory monitoring and virologic outcomes would not differ significantly based on insurance type. We compared HIV monitoring with outcomes among people with HIV (PWH) with private (commercial payer) versus public (Medicare, Medicaid) insurance receiving care at community and hospital clinics. The DC Cohort follows over 8000 PWH from 14 clinics. We included those ≥18 years old enrolled between 2011 and 2015 with stable insurance. Outcomes included frequency of CD4 count and HIV RNA monitoring (> 2 lab measures/year, > 30 days apart) and durable viral suppression (VS; HIV RNA < 50 copies/mL at last visit and receiving antiretroviral therapy (ART) for ≥12 months). Multivariable logistic regression models examined impact of demographic and clinical factors. Among 3908 PWH, 67.9% were publicly-insured and 58.9% attended community clinics. Compared with privately insured participants, a higher proportion of publicly insured participants had the following characteristics: female sex, Black race, heterosexual, unemployed, and attending community clinics. Despite less lab monitoring, privately-insured PWH had greater durable VS than publicly-insured PWH (ART-naive: private 70.0% vs public 53.1%, p = 0.03; ART-experienced: private 80.2% vs public 69.4%, p < 0.0001). Privately-insured PWH had greater durable VS than publicly-insured PWH at hospital clinics (AOR = 1.59, 95% CI: 1.20, 2.12; p = 0.001). Paradoxical differences between HIV monitoring and durable VS exist among publicly and privately-insured PWH in Washington, DC. Programs serving PWH must improve efforts to address barriers creating inequity in HIV outcomes.
Mobilization, Management, and the Modern American Presidency

Presidents mobilize the electorate and manage the state. As in other modern democracies, the assumption is that these two features of national political leadership are complementary, essential features of good government. In America, however, the relationship between political mobilization and presidential management has always been fraught, and in 2016, the candidates divvied up the job description, forcing a stark choice between an insurgent promising to hold the government to account and an inside operative promising to make the government work. This problem can be traced back to the constitutional construction of the presidency, where the popular connection was purposefully attenuated in pursuit of management without mobilization. Though that proved a non-starter, subsequent adaptations have had the characteristic drawbacks of add ons; they have jerry-rigged the machinery without ever producing a coherent synthesis. In the Trump presidency, where we find management completely submerged in mobilization, the problem has finally come home to roost.
CHAPTER I – Distributions

Publisher Summary This chapter discusses what motivates the notion of distribution. Testing the functions of compact support mirror the distributions of arbitrary support, while testing the functions of arbitrary support reflect the distributions of compact support. The smoothness of the testing functions implies that of the distributions. The coarseness of the testing functions, that is, their lack of smoothness, reflects in the coarseness of the corresponding duals. The chapter discusses a class of distributional spaces. It focuses on the significant extension of the notion of Fourier transform; it introduces testing functions together with its dual.
Metallo-β-lactamase domain-containing protein 2 is S-palmitoylated and exhibits acyl-CoA hydrolase activity

Members of the metallo-β-lactamase (MBL) superfamily of enzymes harbor a highly conserved αββα MBL-fold domain and were first described as inactivators of common β-lactam antibiotics. In humans, these enzymes have been shown to exhibit diverse functions, including hydrolase activity toward amides, esters, and thioesters. An uncharacterized member of the human MBL family, MBLAC2, was detected in multiple palmitoylproteomes, identified as a zDHHC20 S-acyltransferase interactor, and annotated as a potential thioesterase. In this study, we confirmed that MBLAC2 is palmitoylated and identified the likely S-palmitoylation site as Cys254. S-palmitoylation of MBLAC2 is increased in cells when expressed with zDHHC20, and MBLAC2 is a substrate for purified zDHHC20 in vitro. To determine its biochemical function, we tested the ability of MBLAC2 to hydrolyze a variety of small molecules and acylprotein substrates. MBLAC2 has acyl-CoA thioesterase activity with kinetic parameters and acyl-CoA selectivity comparable with acyl-CoA thioesterase 1 (ACOT1). Two predicted zinc-binding residues, Asp87 and His88, are required for MBLAC2 hydrolase activity. Consistent with a role in fatty acid metabolism in cells, MBLAC2 was cross-linked to a photoactivatable fatty acid in a manner that was independent of its S-fatty acylation at Cys254. Our study adds to previous investigations demonstrating the versatility of the MBL-fold domain in supporting a variety of enzymatic reactions.
A New Panel Dataset for Studies Using Substate Units of Analysis and Indicators of Drug Activity

This research note reports on the creation of a new panel dataset using multiple waves of substate estimates from the National Survey on Drug Use and Health. It also provides identifying informatio...
Evaluation of optimal timing for post-treatment imaging after primary chemoradiotherapy in patients with locally advanced cervical cancer

Objectives: Computed tomography (CT) and positron emitted tomography (PET) are used to assess disease response to chemoradiotherapy in locally advanced cervical cancer (LACC), however inconclusive imaging leads to repeat studies, biopsies and added cost. This study aimed to determine optimal timing of post-treatment imaging to optimize detection of residual disease and lower cost without impairing outcomes. Methods: We performed a retrospective review of 260 patients (pts) with LACC who received primary chemoradiotherapy or radiation at a single institution between 2009 and 2020. Demographic and clinical information was abstracted from medical records. Pts had at least one post-treatment CT or PET. Primary outcome was accuracy of post-treatment imaging as measured by Area Under the Curve (AUC) with AUC = 1 indicating perfect prediction. Pts were grouped by imaging timing: 0-2 months (mos), 2-4 mos, 4-6 mos, or >6 mos. Statistical tests were analysis of variance, chi-square, and Cox proportional hazards. Results: 156 pts were included. Median age at diagnosis was 51 yrs, 57% were White, and 35% had private insurance. 78% had squamous histology, 60% had stage III disease, 78% underwent PET and 22% underwent CT. The most common timing for imaging was 2-4 mos (43%), followed by 4-6 mos (22%), >6 mos (22%), and 0-2 mos (13%). A trend toward later imaging was seen in Black pts (37% Black vs 53% White 0-2 mos, 16% Black vs 66% White 2-4 mos, 31% Black vs 57% White 4-6 mos, 46% Black vs 43% White, >6 mos p=0.15). A similar trend occurred comparing uninsured and insured pts (0-2 mos 21% vs 58%, 2-4 mos 28% vs 39%, 4-6 mos 29% vs 37%, >6 mos 31% vs 14%, p=0.08). Post-treatment imaging, regardless of timing, was an accurate indicator of complete response (negative predictive value 99%). Imaging performed between 0-2 mos had the highest AUC, 1.0 (p 6 mos (AUC 0.94, p=0.007), 4-6 mos (AUC 0.8, p=0.77), and 2-4 mos (AUC 0.78, ref). Pts with imaging at 2-4 mos were more likely to need repeat imaging (0% (0-2 mos), 22% (2-4 mos), 6% (4-6 mos), and 6% (> 6 mos) [p Conclusions: Though limited by sample size and retrospective design, these data suggest that imaging 2-4 mos post-treatment for LACC leads to increased need for repeat imaging likely due to indeterminate results. We suspect the high performance of 0-2 mo and >6 mo scans were influenced by selection bias; pts who received imaging 6mo group had surpassed the time during which post-treatment effect was evident on PET, and also likely had high concordance with concerning exam findings. While no survival differences were noted, further study is needed to determine timing of post-treatment imaging that optimizes assessment of treatment response while avoiding unnecessary interventions and preserving patient outcomes.
[Advances in the Treatment of RET Fusion-Positive Advanced Non-Small-Cell Lung Cancer].

Rearranged during transfection (RET) fusions are found in 0.7% to 2% of non-small cell lung cancers (NSCLC). Fusions between RET gene and other domains represent the distinct biological and clinicopathological subtypes of NSCLC. Recent years have witnessed the remarkable advancement of RET fusion-positive advanced NSCLC therapy. Conventional chemotherapy produced moderate clinical benefits. Prior to the introduction of targeted therapy or in the context of unavailability, platinum-based systemic regimens are initial therapy options. Immunotherapy predicted minimal response in the presence of RET fusions while currently available data have been scarce, and the single-agent immunotherapy or in combination with chemotherapy regimens are not recommended as initial systemic therapy in this population. The repurpose of multi-target kinase inhibitors in patients with RET fusion-positive NSCLC showed encouraging therapeutic activity, with only cabozantinib and vandetanib being recommended as initial or subsequent options under certain circumstances. However, there are still unmet clinical needs. Pralsetinib and selpercatinib have been developed as tyrosine kinase inhibitors (TKI) selectively targeting RET variation of fusions or mutations, and both agents significantly improved the prognosis of patients with RET fusion-positive NSCLC. Pralsetinib and selpercatinib have been established as preferred first-line therapy or subsequent therapy options. As observed with other TKIs treatment, resistance has also been associated with RET targeted inhibition, and the acquired resistance eventually affect the long-term therapeutic effectiveness, leading to limited subsequent treatment options. Therefore, it is essential to identify resistance mechanisms to TKI in RET fusion-positive advanced NSCLC to help reveal and establish new strategies to overcome resistance. Here, we review the advances in the treatment of RET fusion-positive advanced NSCLC. .
Far-field brainstem responses evoked by vestibular and auditory stimuli exhibit increases in interpeak latency as brain temperature is decreased.

The effect of decreasing of brain temperature on the brainstem auditory evoked response (BAER) in rats was investigated. Voltage pulses, applied to a piezoelectric crystal attached to the skull, were used to evoke stimuli in the auditory system by means of bone-conducted vibrations. The responses were recorded at 37 C and 34 C brain temperatures. The peaks of the BAER recorded at 34 C were delayed in comparison with the peaks from the 37 C wave, and the later peaks were more delayed than the earlier peaks. These results indicate that an increase in the interpeak latency occurs as the brain temperature is decreased. Preliminary experiments, in which responses to brief angular acceleration were used to measure the brainstem vestibular evoked response (BVER), have also indicated increases in the interpeak latency in response to the lowering of brain temperature.
Ways of Bureaucracy

What attributes should a manager of new technology possess? The Kellex story suggests some answers.
Engineering in the Soil Conservation Service

Outlines of engineering activities of Soil Conservation Service with particular emphasis on engineering aspects of new Watershed Protection and Flood Prevention Program, Public Law 566.
Structural characterization of Escherichia coli phosphatidylserine decarboxylase.

Phosphatidylserine decarboxylase of Escherichia coli is one of a small group of pyruvoyl-dependent enzymes (Satre, M., and Kennedy, E.P. (1978) J. Biol. Chem. 253, 479-483). The DNA sequence of the structural gene (psd) and partial protein sequence studies demonstrate that the enzyme contains two nonidentical subunits, alpha (Mr = 7,332) and beta (Mr = 28,579), which are derived from a single proenzyme. These two subunits are blocked at their respective amino termini. Reduction of the enzyme with NaCNBH3 in the presence of radiolabeled phosphatidylserine resulted in association of the label with the alpha subunit. Similar reduction in the presence of ammonium ions exposed a new amino terminus for the alpha subunit beginning with alanine. Therefore, the pyruvate prosthetic group is in amide linkage to the amino terminus of the alpha subunit. The amino terminus of the beta subunit was determined to be formylmethionine. The carboxyl terminus of the beta subunit was determined to be glycine as predicted by the DNA sequence. Comparison of the DNA sequence and protein sequence information revealed that the decarboxylase is made as a proenzyme (Mr = 35,893), and the predicted amino acid at the position of the pyruvate within the open reading frame of the proenzyme is serine. Therefore, as with other pyruvoyl-dependent decarboxylases, the prosthetic group is derived from serine through a post-translational cleavage of a proenzyme.
Untangling the Privacy Paradox in Arbitration

Arbitration is private but not secret. This truism regarding arbitration seems contradictory and nonsensical. However, common understandings of privacy in arbitration often lull individuals into assuming personal information revealed in arbitration may not become public. They assume privacy and confidentiality are synonymous. The reality is that arbitration is private but not necessarily confidential, or secret. This is the privacy paradox: it defies common conceptions of arbitration's secrecy, but is nonetheless true. This paradox is problematic because it leads to shortsighted contracting and simplistic assumptions about arbitral justice. Moreover, it may foster injustice when repeat players unduly benefit from unpublished awards as well as pro-drafter confidentiality provisions. This Article thus calls contracting parties to more carefully draft their arbitration contracts, and invites policymakers to craft transparency reforms that consider tensions created by the privacy paradox. It seeks to spark discussion of multi-perspective transparency reforms by proposing a two-prong approach toward transparency: (1) Require publication of arbitration awards in arbitrations involving statutory discrimination, consumer protection, corruption, and fraud; and (2) Establish default rules protecting personal and proprietary information from use or disclosure outside of arbitration hearings. The key is to balance all parties' interests in confidentiality and privacy with the public's legitimate interests in accessing information that may affect health, safety or wellbeing. Indeed, tempered and properly guided secrecy standards could enhance arbitration's value for disputing parties, as well as the public.