cssi/SciSciGPT-SciSciNet huggingface dataset:
Bioinformatics Workflow for Clinical Whole Genome Sequencing at Partners HealthCare Personalized Medicine.

Effective implementation of precision medicine will be enhanced by a thorough understanding of each patient’s genetic composition to better treat his or her presenting symptoms or mitigate the onset of disease. This ideally includes the sequence information of a complete genome for each individual. At Partners HealthCare Personalized Medicine, we have developed a clinical process for whole genome sequencing (WGS) with application in both healthy individuals and those with disease. In this manuscript, we will describe our bioinformatics strategy to efficiently process and deliver genomic data to geneticists for clinical interpretation. We describe the handling of data from FASTQ to the final variant list for clinical review for the final report. We will also discuss our methodology for validating this workflow and the cost implications of running WGS.
Interlinking life-cycle data spaces to support decision making in highway asset management

Abstract Technology advances have changed highway project delivery and asset management from relying on 2D paper documents to n-D digital data sets. However, the implementation of diverse software applications imposes big challenges for integrating life-cycle data to support decision making in highway asset management due to the potential inconsistencies of levels of detail, data syntax and semantics. This paper presents an ontology based exchange mechanism that enables unification and interconnection of life-cycle data spaces to support decision making in highway asset management. The mechanism consists of the following key components: (1) domain and merged ontologies, (2) data wrappers and (3) a data query and reasoning system. The mechanism was tested on a sample roadway project retrieved from Landxml.org , and the results indicated the success in integrating fragmented life-cycle data spaces and extracting information for asset management.
Differential diagnosis and treatment of intractable seizures.

Not all intractable seizures are due to epilepsy, and episodes of uncertain origin call for assessment by appropriate diagnostic methods. Once the disorder is found to be epileptic in nature, seizures can be controlled in many patients. Techniques of diagnosis and treatment are reviewed.
Aerodynamic Sensitivity Analysis based on Modified Navier-Stokes Equations

T he use of gradient-based optimization algorithms is highly advantageous for aerodynamic design of fluid-structure interaction (FSI) problems. A typical scheme involves techniques to calculate the solution of the Navier-Stokes equations and also the sensitivity response. Usually, due to use of body conformal meshes, modifying the mesh topology is required when changing the shape of immersed solid. This becomes cumbersome when the boundaries are complex. In this research, we introduce a method based on adding force terms to the Navier-Stokes equations to decouple the solid boundary definition from the mesh. Therefore, the governing equations can be solved on a Cartesian grid with efficient solvers. Decoupling the solid boundary from the mesh enables us to deform the solid domain without modifying the mesh. This allows a significant reduction in computational costs. To calculate the sensitivity response of the system, the continuum sensitivity method is used. Using the force terms to represent the solid boundaries, the convective terms are removed in boundary conditions sensitivity equations. This is because the boundaries do not depend on domain configuration. The methodology is verified using the laminar flow over a circular cylinder. The force terms are applied using the regularized Heaviside function to satisfy the no-slip condition in the solid domain. The results show the applicability of this method for solving the governing equations and also the sensitivity response for flow fields with low Reynolds numbers.
User cost model of highway work zone during discrete periods under influence of uncertain factors

The traffic situation of highway work zone during discrete periods was analyzed.By dispersing the work periods,the relationships between the capacities of work zones and user costs during different discrete periods were compared,and the calculation models of user costs during corresponding periods were set up.The uncertain factors of user cost for highway work zone were analyzed.Based on the probability distributions of uncertain factors,the fluctuation scope of user cost was predicted by using Monte Carlo simulation and verified by the example of Qinglian Highway.Calculation result indicates by using the proposed model,the average user cost under the day-time work scheme is 193 148 021yuan,and the maximum and minimum costs are 466 820 060, 117 342 849yuan respectively.The average user cost under the night-time work scheme is 1 795 047yuan,and the maximum and minimum costs are 3 443 468,1 417 274 yuan respectively.It is found that the application of proposed model can show the influences of uncertain factors well.3tabs,5figs,18refs.
MANUALIZATION, FEASIBILITY, AND EFFECTIVENESS OF THE SCHOOL‐BASED SOCIAL COMPETENCE INTERVENTION FOR ADOLESCENTS (SCI‐A)

Despite the movement toward identification of evidence-based practices (EBPs), there is a discrepancy in the availability of school-based EBPs targeting the unique needs of students with high functioning forms of autism and related social needs. Based on calls for systematic intervention development and evaluation processes, the current study describes the manualization, feasibility, and effectiveness testing of the school-based Social Competence Intervention for Adolescents (SCI-A) curriculum. School personnel were trained to implement SCI-A to a targeted student population. Fidelity and social validity data indicated curriculum feasibility and acceptability within secondary school settings. Student social functioning, executive functioning, and theory of mind demonstrated postintervention gains with moderate effect sizes. Results are promising for SCI-A's continued positive trajectory within the phases of EBP evaluation research. Challenges for intervention effectiveness testing within schools and future considerations for evaluating EBPs are discussed.
The Place of Ionizing Radiation in the Treatment of Thyroid Carcinoma

The use of ionizing radiation is not confined to the treatment of metastatic disease. Indeed, in undifferentiated tumors the treatment of choice is ionizing radiation, utilizing refined dosimetry and the sophisticated equipment available today. However, one must not forget the important palliation and prophylaxis that ionizing radiation can achieve in patients with metastases from the differentiated as well as undifferentiated forms of thyroid carcinoma.
THE FATE OF PESTICIDE PLANT METABOLITES IN VERTEBRATES

Plant metabolites of pesticides may be classified into three broad groups: free compounds, conjugates, and bound residues. The most characteristic of all plant conjugates are glucose derivatives known as glucosides. In the monogastric animal, glucosides are readily absorbed and partially hydrolyzed to the free exocons which may undergo further metabolism before being reconjugated and eliminated as typical mammalian sulfate or glucuronide conjugates. The glucoside does not undergo direct oxidation to the corresponding glucuronide. In ruminants, complete hydrolysis of the glucoside occurs in the rumen before the liberated exocons undergo further metabolism, reconjugation, and elimination. Unlike glucosides, bound residues pass through the gastrointestinal tract of the rat unchanged. The fate of bound residues in the ruminant is less clear and may depend on the type of material to which the residue is bound.
A Survey of Inflation Theory

Since 1945 the geographical extent and temporal stubbornness of The Great Inflation 2 have shaken many economists’ faith in the orthodoxies of preceding generations. Neo-orthodoxies, including restatements, are only dimly in evidence. Our survey is accordingly more of a guide through chaos than a history of received doctrine or a systematic critique of a few rival positions.
Neonatal Myasthenia Gravis

The advantages of electrodiagnosis in a premature infant with neonatal myasthenia gravis are proposed by the Dept of Rehabilitation Medicine, Children’s Hospital and Medical Center, Univ of Washington School of Medicine, Seattle, WA.
The History and Physical Examination of the Cardiovascular System

In this chapter, we outline the general approach to the patient with known or suspected cardiovascular disease with specific emphasis on the history and physical examination. Time constraints challenge the development of a detailed history, yet a properly obtained patient narrative can serve to guide the examination and subsequent diagnostic testing. Special attention should be given to the family history as genetic testing and personalized medicine grow in importance. A general examination that includes assessment of the major organ systems, coupled with specific attention to the venous and arterial waveforms, as well as inspection, palpation, and auscultation of the heart, makes for a complete cardiovascular evaluation. This chapter provides a guide to recognizing and applying the findings on physical examination to the diagnosis and assessment of a variety of cardiovascular disorders. The history and physical examination constitute the foundation of the doctor-patient relationship and should serve as the springboard for diagnosis and management.
Revisional bariatric surgery: A review of the current recommendations

Revisional bariatric surgery is increasingly becoming popular as the number of primary procedures for the treatment of obesity gains popularity. It is estimated that about 10% of patients who underwent a bariatric procedure will need revisional surgery. The most common indications for revisional bariatric surgery are inadequate weight loss (<25% of excess body weight loss) and weight regain (gain of more than 10 kg based on the nadir weight); however, procedure-specific complications are also indication of the need for revisional surgery. In this article, we review the current most common bariatric procedures with its complications, indications for revision, alternative procedures, and outcomes.
Impaired Signal Transduction in Tumor Infiltrating T Cells from Patients with Renal Cell Carcinoma

T cell activation in response to antigen requires interaction of multiple receptor-coreceptor pairs (1–3). Important outcomes of T cell stimulation include cellular proliferation, cytokine secretion and cytotoxic activity (1). The induction of these various functions is dependent on the activation of intracellular signal transduction pathways which are linked to the different receptors (4). Activation of the T-cell receptor complex (TCR-CD3) involves antigen recognition through the α /β subunits and intracellular signaling via CD3 (γ,δ,e) and ζ chains (1,2,5). Tyrosine phosphorylation of several proteins such as TCR ζ, CD3 e, and phospholipase C- γ represent an important early event (1,2, 4–6). Three different proteins kinases (PTK) have been implicated in TCR/CD3 signaling and they include p56lck, p59fyn and ZAP-70 (2,4,5,7–9). Tyrosine phosphorylation leads to several intermediate signaling events that include the formation of second messengers and the activation of serine/threonine kinases along with phosphatases which are important for downstream gene expression (4). IL2 binding to its receptor is an important step in T cell activation and proliferation (10). This receptor is a trimolecular complex in which the IL2Rα chain is necessary for high affinity receptor expression while the β and γ chains are involved in signal transduction (11–14). Although the IL2R signaling pathway is not well defined, tyrosine phosphorylation of several substrates appears to be an essential early event (12,14–16).
Propidium—a Fluorescence Probe for a Peripheral Anionic Site on Acetylcholinesterase

Propidium (3, 8-diamino-5, 39-diethylmethylamino-n-propyl-6-phenylphenanthridium) diiodide binds with high affinity to a purified acetylcholinesterase isolated by lytic procedures from Torpedo californica. Complex formation results in 10-fold enhancement of fluorescence for the ligand in the bound state. The fluorescent ligand can be dissociated from the enzyme by back-titration with d-tubocurarine and gallamine under conditions of low ionic strength (Γ/2 ≅ 0.001). At higher ionic strength, in 0.1 M NaCl, 0.04 M MgCl2, and 0.01 M Tris-Cl, pH 8.0 (Γ/2 = 0.23), the above ligands are relatively ineffective in dissociating propidium from the enzyme. Edrophonium, an inhibitor that appears specific for the active center, does not dissociate propidium under conditions of high and low ionic strength. This specificity is consistent with propidium acting as a fluorescence probe for a peripheral anionic site on acetylcholinesterase.
Tribes Cymbidieae and Epidendreae

Eulophia alta and E. ecristata occur in North America north of Florida and Mexico, but their pollination has not been studied here. Although autogamy has been reported elsewhere, a recent Florida study of E. alta found that autogamy was rare and produced seeds that developed more slowly than seed produced by other treatments. Morphology of the flower of Epidendrum magnoliae, along with its production of an intense nocturnal fragrance, suggests pollination by nocturnal moths. Hexalectris revoluta var. colemanii is an obligate outbreeder, whereas H. nitida, H. spicata var. arizonica, and H. revoluta var. revoluta are autogamous. H. revoluta and H. nitida appear to be resource limited.
Functional and structural consequences of chemokine (C-X-C motif) receptor 4 activation with cognate and non-cognate agonists.

Chemokine (C-X-C motif) receptor 4 (CXCR4) regulates cell trafficking and plays important roles in the immune system. Ubiquitin has recently been identified as an endogenous non-cognate agonist of CXCR4, which activates CXCR4 via interaction sites that are distinct from those of the cognate agonist C-X-C motif chemokine ligand 12 (CXCL12). As compared with CXCL12, chemotactic activities of ubiquitin in primary human cells are poorly characterized. Furthermore, evidence for functional selectivity of CXCR4 agonists is lacking, and structural consequences of ubiquitin binding to CXCR4 are unknown. Here, we show that ubiquitin and CXCL12 have comparable chemotactic activities in normal human peripheral blood mononuclear cells, monocytes, vascular smooth muscle, and endothelial cells. Chemotactic activities of the CXCR4 ligands could be inhibited with the selective CXCR4 antagonist AMD3100 and with a peptide analogue of the second transmembrane domain of CXCR4. In human monocytes, ubiquitin- and CXCL12-induced chemotaxis could be inhibited with pertussis toxin and with inhibitors of phospholipase C, phosphatidylinositol 3 kinase, and extracellular signal-regulated kinase 1/2. Both agonists induced inositol trisphosphate production in vascular smooth muscle cells, which could be inhibited with AMD3100. In β-arrestin recruitment assays, ubiquitin did not sufficiently recruit β-arrestin2 to CXCR4 (EC50 > 10 μM), whereas the EC50 for CXCL12 was 4.6 nM (95% confidence interval 3.1–6.1 nM). Both agonists induced similar chemical shift changes in the 13C-1H-heteronuclear single quantum correlation (HSQC) spectrum of CXCR4 in membranes, whereas CXCL11 did not significantly alter the 13C-1H-HSQC spectrum of CXCR4. Our findings point towards ubiquitin as a biased agonist of CXCR4.
The littoral Drift Problem at Shoreline Harbors

For shoreline harbors where littoral drift occurs along shoreline, certain design, construction, and maintenance problems are present; summary of basic considerations in generalized terms; case histories of typical shoreline harbors for which operational information extending over long period of years is available. (64 refs.)
Emergency department length of stay for ethanol intoxication encounters.

Abstract Background Emergency Department (ED) encounters for ethanol intoxication are becoming increasingly common. The purpose of this study was to explore factors associated with ED length of stay (LOS) for ethanol intoxication encounters. Methods This was a multi-center, retrospective, observational study of patients presenting to the ED for ethanol intoxication. Data were abstracted from the electronic medical record. To explore factors associated with ED LOS, we created a mixed-effects generalized linear model. Results We identified 18,664 eligible patients from 6 different EDs during the study period (2012–2016). The median age was 37 years, 69% were male, and the median ethanol concentration was 213 mg/dL. Median LOS was 348 min (range 43–1658). Using a mixed-effects generalized linear model, independent variables associated with a significant increase in ED LOS included use of parenteral sedation (beta = 0.30, increase in LOS = 34%), laboratory testing (beta = 0.21, increase in LOS = 23%), as well as the hour of arrival to the ED, such that patients arriving to the ED during evening hours (between 18:00 and midnight) had up to an 86% increase in LOS. Variables not significantly associated with an increase in LOS included age, gender, ethanol concentration, psychiatric disposition, using the ED frequently for ethanol intoxication, CT use, and daily ED volume. Conclusion Variables such as diagnostic testing, treatments, and hour of arrival may influence ED LOS in patients with acute ethanol intoxication. Identification and further exploration of these factors may assist in developing hospital and community based improvements to modify LOS in this population.
Problems in Achieving Health-Care Reform

A serious problem with the concept of MC is that similar arrangements have not contained costs; administrative costs in U.S. hospitals are exorbitant. Woolhandler, Himmelstein, and Lewontin (1993) studied administrative costs for virtually all acute-care hospitals in the United States in 1990. Hospital administration accounted for an average of 24.8% of total costs (twice as high as those in Canada), ranging from 20.5% to 30.6% for individual hospitals. A discouraging fact was that administrative costs were not lower, but were slightly higher in states in which health-care management organization (HMO) enrollments included more than 25% of the population (California, Massachusetts, Minnesota, and Oregon—administrative costs were 25.6%) as compared to those with low HMO enrollment (administrative costs were 24.6%). This suggests that introducing MC will not solve the problem of high administrative costs—at least it did not in those states. No state had administrative costs as low as the 9–11% reported for Canadian hospitals, or the 10–15% reported for France. The 24.8% estimate of administrative costs in the United States is too low, because it did not include most hospital advertising and marketing costs, which add another 1% to total hospital costs, nor did it include clinical expenses for clerical personnel in clinical units, such as ward clerks, receptionists, and secretaries.
Toxic Plants: What the Horse Practitioner Needs to Know

Horses poisoned by a plant may show a myriad of clinical signs. Awareness of the poisonous plants growing in a given area and those that are likely to appear in hay and their associated clinical signs can be instrumental in making diagnoses. More importantly, the information can be shared with clients to help prevent plant poisonings in horses. This article offers a discussion of the geographical distributions, descriptions, toxic agents, mechanisms, clinical signs, prognoses, and necropsy findings for poisonous plants affecting equine practice.
Abstract WP93: Long-term Use of the Grip Strength and Automated Von Frey Tests in the Mouse Photothrombotic Model of Stroke

Improvement of impaired neurological function(s) is a primary endpoint in experimental stroke recovery studies, making the choice and nature of the functional tests crucial for proper execution and...
Environmental impact assessments of heat pump–gas fired water heater hybrid system for space heating application

Hybrid systems combining heat pump and gas heater can demonstrate the economic benefits, while their environmental performance is rarely investigated. In this paper, a comprehensive environmental performance investigation has been conducted to reveal the potential for emission reductions. A new environmental impact methodology has been built, and various influencing factors are evaluated. In respect of the climates, the hourly energy consumption emission first increases and then declines, which is the result of multiple effects from the weighting factors of fuel source emissions and each heating sector’s performance. Under the operation condition map for the current study, the effects of the target (final) water temperatures, electricity generation emission factor reduction, and price ratios are revealed to be the top 3 heaviest fluctuations for emissions for hourly system operation energy consumption, followed by each heating sector’s efficiency enhancements. The environmental impacts due to hourly system operation do not closely follow the hourly energy consumption profile for the effect of climate conditions and can be quite opposite when considering the effect of fuel source price ratios. In addition, the lifetime environmental performance has been examined for typical cities in China. In the cold region, such as Shenyang, the emission due to the natural gas contributor shares more than 46% of the total emissions. For warm cities (Shanghai, Wuhan, and Chengdu), the emission of the natural gas is only responsible for ~ 9% or even less of the total emissions. A switch from R410A (GWP100:1924) to R452B (GWP100:675) can also lead to ~ 11% emission total reductions for city of Shanghai, Wuhan, and Chengdu. It is anticipated that the viewpoints and insights from this study can be beneficial for the engineers, policymakers, scholars, public, and manufactures to maintaining the maximum sustainability and economic benefits.
Loss of bronchoprotection with ICS plus LABA treatment, β-receptor dynamics, and the effect of alendronate

Background Loss of bronchoprotection (LOBP) with a regularly used long-acting β2-adrenergic receptor agonist (LABA) is well documented. LOBP has been attributed to β2-adrenergic receptor (B2AR) downregulation, a process requiring farnesylation, which is inhibited by alendronate. Objective We sought to determine whether alendronate can reduce LABA-associated LOBP in inhaled corticosteroid (ICS)–treated patients. Methods We conducted a randomized, double-blind, placebo-controlled, parallel-design, proof-of-concept trial. Seventy-eight participants with persistent asthma receiving 250 μg of fluticasone twice daily for 2 weeks were randomized to receive alendronate or placebo while initiating salmeterol for 8 weeks. Salmeterol-protected methacholine challenges (SPMChs) and PBMC B2AR numbers (radioligand binding assay) and signaling (cyclic AMP ELISA) were assessed before randomization and after 8 weeks of ICS plus LABA treatment. LOBP was defined as a more than 1 doubling dose reduction in SPMCh PC20 value. Results The mean doubling dose reduction in SPMCh PC20 value was 0.50 and 0.27 with alendronate and placebo, respectively (P = .62). Thirty-eight percent of participants receiving alendronate and 33% receiving placebo had LOBP (P = .81). The after/before ICS plus LABA treatment ratio of B2AR number was 1.0 for alendronate (P = .86) and 0.8 for placebo (P = .15; P = .31 for difference between treatments). The B2AR signaling ratio was 0.89 for alendronate (P = .43) and 1.02 for placebo (P = .84; P = .44 for difference). Changes in lung function and B2AR number and signaling were similar between those who did and did not experience LOBP. Conclusion This study did not find evidence that alendronate reduces LABA-associated LOBP, which relates to the occurrence of LOBP in only one third of participants. LOBP appears to be less common than presumed in concomitant ICS plus LABA–treated asthmatic patients. B2AR downregulation measured in PBMCs does not appear to reflect LOBP.
Beyond Traditional Response to Intervention: Helping Rural Educators Understand English Learners’ Needs:

Response to intervention (RTI) allows schools to support the academic success of English learners (ELs) while helping educators rule out cultural or linguistic differences and educational backgroun...
Breast Adipocyte Co-culture Increases the Expression of Pro-angiogenic Factors in Macrophages.

Obese individuals with breast cancer have a poorer prognosis and higher risk of metastatic disease vs. non-obese patients. Adipose tissue in obese individuals is characterized by an enhanced macrophage infiltration, creating a microenvironment that favors tumor progression. Here, we demonstrate a role for adipocyte-macrophage interactions in the regulation of angiogenesis. Co-culture of THP-1 macrophages with human breast adipocytes led to increased expression of the pro-angiogenic growth factor, vascular endothelial growth factor A (VEGFA). Several adipocyte-derived proteins including leptin, insulin, IL-6, and TNF-alpha were each capable of increasing VEGFA expression in THP-1 macrophages, identifying these as possible mediators of the changes that were observed with co-culture. Furthermore, analysis of THP-1 culture media by antibody array revealed that THP-1 secrete several other pro-angiogenic signals in response to adipocyte co-culture, including interleukin 8 (IL-8), matrix metalloproteinase 9 (MMP9), pentraxin 3 (PTX3), and serpin E1 (plasminogen activator inhibitor 1, PAI1) after co-culture with human adipocytes. We used an in vitro endothelial tube formation assay with human vascular endothelial cells to evaluate the effects of THP-1 culture media on angiogenesis. Here, culture media from THP-1 cells previously exposed to human adipocytes stimulated endothelial tube formation more significantly than THP-1 cells cultured alone. In summary, we find that adipocyte co-culture stimulates the expression of pro-angiogenic mediators in macrophages and has pro-angiogenic effects in vitro, thus representing a possible mechanism for the enhanced risk of breast cancer progression in obese individuals.
The Influence of a University Homeschool Physical Education Program on Fundamental Motor Skills and Self-Confidence

Individuals are both more likely to participate in sports, exercise, and physical activity when they are skilled. Therefore, motor skills and skilled movement should be viewed as prerequisites to a physically active lifestyle. Children and adolescents who have achieved fundamental motor competence are also believed to perceive themselves as being competent although there is inconsistency in the results so far reported in the literature. Despite the unprecedented growth home homeschool education, studies have not examined the development of motor competency of homeschool students or its relationship to confidence. The current investigation examined the influence fundamental motor skill development and self-confidence of students enrolled in a university homeschool physical education program. Results from the pre-test (M = 13.92, SD = 2.8) and post-test (M = 20.75, SD = 3.5) fundamental motor skill observations indicate that the homeschool program led to an improvement in overall skill, t(52) = 12.05, p< .001 (E.S. = 1.06). Dependent-samples t -test produced significant results from pre to post for research participants [t (1,52) = 27.26 , p<.05, E.S. = 1.10], who improved their self-efficacy over the course of the study [baseline M self-efficacy = 71.92, SD= 16.52, endline M self-efficacy = 88.87, SD =15.34]. This study showed that a university homeschool physical education program can lead to improvements in the developmental of fundamental motor skills and self-confidence.
Knockdown of liver-derived factor XII by GalNAc-siRNA ALN-F12 prevents thrombosis in mice without impacting hemostatic function.

Abstract Background Plasma coagulation Factor XII (FXII) plays a crucial role in contact activation, ultimately regulating both the kinin-kallikrein system and the intrinsic pathway of coagulation. A growing body of evidence suggests that inhibition of FXII can prevent thrombosis. Given FXII does not appear to modulate hemostasis, targeting FXII is a promising strategy for the prevention of pathological thrombus formation without the hemostatic risks typically associated with anticoagulants. To this end, a subcutaneously administered investigational RNAi therapeutic targeting liver F12 mRNA (ALN-F12) was developed. Aim To investigate the thrombo-protective and hemostatic effects of FXII reduction by ALN-F12 in rodent thrombosis and hemostasis models. Methods A single dose of ALN-F12 was subcutaneously administered to C57Bl/6 mice. After reaching steady state FXII reduction, the impact on thrombosis (ferric chloride arterial thrombosis and electrolytic injury induced venous thrombosis models) and hemostasis (saphenous vein injury and tail tip transection bleeding models) was evaluated. Result Administration of ALN-F12 resulted in dose-dependent reductions of both liver F12 mRNA and plasma FXII protein. In mice, ALN-F12 led to dose-dependent reductions in platelet and fibrin accumulation in the venous electrolytic-injury model and in the time to occlusion in the ferric chloride arterial thrombosis model. At 10 mg/kg ALN-F12, the top dose level evaluated, this resulted in >95% reduction of FXII and ~10 fold reduction in fibrin deposition. Finally, hemostasis models showed that >95% reduction of FXII had no impact on bleeding time or blood loss. Conclusion Our findings support that reduction of plasma Factor XII by ALN-F12 provided thrombo-protective effects with no increased bleeding risk in rodent models of thrombosis and hemostasis.
Treatment of aplastic anemia.

Results of treating aplastic anemia patients with immunosuppressive therapy in Seattle are compared with those obtained at other centers. Our clinical experience in HLA- identical marrow transplantation for severe aplastic anemia is reviewed in the context of clinical results of other transplantation centers. Approaches taken to overcome the problem of graft rejection and minimize the incidence and severity of acute and chronic graft-versus-host disease are discussed.
Localizability and elementary particles

The well-definedness of particles of any kind depends on the limits, approximations, or other conditions that may or may not be involved, for example, whether there are interactions and whether ostensibly related energy is localizable. In particular, their theoretical status differs between its non-relativistic and relativistic versions: One can properly define interacting elementary particles in single-system non-relativistic quantum mechanics, at least in the case of non-zero mass systems; by contrast, one is severely challenged to define even these properly in the relativistic quantum field theories that now underlie the study of particle physics. Here, the impact of localizability on this status is reviewed in relation to the work of Paul Busch on positive operator valued measures that significantly probes the relevance of quantum unsharpness to it.
Liver transplantation: expanding the donor and recipient pool

Liver transplantation is an exemplar model of complex surgery and the only curative option for patients with end-stage liver disease. Although historically associated with poor outcomes, liver cancer management has also been revolutionised with liver transplantation and in some instances, survival outcomes are comparable to surgical resection. As such, the key elements underpinning the major advances in surgical technique, immunological therapies and allocation policies combined with improved patient and graft survival outcomes have created a huge demand for organ donation. Despite improvements in donor and recipient selection, there is a persistent disparity between organ supply and demand. Candidate wait-list mortality and dropout rates remain problematic and this concern has resulted in increased efforts to expand the donor pool to meet the unmet needs of the population. This is even more challenging when coupled with an ever-growing recipient pool, candidate waiting lists and an ageing population. Over the past two decades, there has been a considerable focus on extended criteria organs, donations after cardiac death and alternative avenues for marginal liver use. With careful donor selection and recipient matching, these livers may help bridge the gap between supply and demand and placate the ever-expanding recipient pool. Here, we present a summary of recent developments by the transplant community addressing the issues of a growing donor and recipient pool.
High-protein vs. standard-protein diets in overweight and obese patients with heart failure and diabetes mellitus: findings of the Pro-HEART trial

Author(s): Evangelista, Lorraine S; Jose, Mini M; Sallam, Hanaa; Serag, Hani; Golovko, George; Khanipov, Kamil; Hamilton, Michele A; Fonarow, Gregg C | Abstract: AimsThe intermediate-term effects of dietary protein on cardiometabolic risk factors in overweight and obese patients with heart failure and diabetes mellitus are unknown. We compared the effect of two calorie-restricted diets on cardiometabolic risk factors in this population.Methods and resultsIn this randomized controlled study, 76 overweight and obese (mean weight, 107.8n±n20.8nkg) patients aged 57.7n±n9.7nyears, 72.4% male, were randomized to a high-protein (30% protein, 40% carbohydrates, and 30% fat) or standard-protein diet (15% protein, 55% carbohydrates, and 30% fat) for 3nmonths. Reductions in weight and cardiometabolic risks were evaluated at 3nmonths. Both diets were equally effective in reducing weight (3.6 vs. 2.9nkg) and waist circumference (1.9 vs. 1.3ncm), but the high-protein diet decreased to a greater extent glycosylated haemoglobin levels (0.7% vs. 0.1%, Pn=n0.002), cholesterol (16.8 vs. 0.9nmg/dL, Pn=n0.031), and triglyceride (25.7 vs. 5.7nmg/dL, Pn=n0.032), when compared with the standard-protein diet. The high-protein diet also significantly improved both systolic and diastolic blood pressure than the standard-protein diet (Pnln0.001 and Pn=n0.040, respectively).ConclusionsBoth energy-restricted diets reduced weight and visceral fat. However, the high-protein diet resulted in greater reductions in cardiometabolic risks relative to a standard-protein diet. These results suggest that a high-protein diet may be more effective in reducing cardiometabolic risk in this population, but further trials of longer duration are needed.
The Patent-Antitrust Debate Annotated

These materials, which originally appeared on the Patently-O blog, address the back-and-forth between Makan Delrahim, the Assistant Attorney General for the Antitrust Division of the Department of Justice, and attorneys both objecting to and supporting his views on standard-essential patents (SEPs) and standard-setting organizations (SSOs). For parties who are interested in this controversy but who do not have time to locate, review, and compare the documents, the materials are annotated with Acrobat sticky notes keyed to highlighting of text, in an effort to emphasize the points of disagreement.
Measurement Precision and Efficiency of Computerized Adaptive Testing for the Activities-specific Balance Confidence Scale in People With Stroke.

Objective Administrative burden often prevents clinical assessment of balance confidence in people with stroke. A computerized adaptive test (CAT) version of the Activities-specific Balance Confidence Scale (ABC CAT) can dramatically reduce this burden. The objective of this study was to test balance confidence measurement precision and efficiency in people with stroke with an ABC CAT. Methods We conducted a retrospective cross-sectional simulation study with data from 406 adults approximately 2-months post-stroke in the Locomotor-Experience Applied Post-Stroke (LEAPS) trial. Item parameters for CAT calibration were estimated with the Rasch model using a random sample of participants (n = 203). Computer simulation was used with response data from remaining 203 participants to evaluate the ABC CAT algorithm under varying stopping criteria. We compared estimated levels of balance confidence from each simulation to actual levels predicted from the Rasch model (Pearson correlations and mean standard error (SE)). Results Results from simulations with number of items as a stopping criterion strongly correlated with actual ABC scores (full item, r = 1, 12-item, r = 0.994; 8-item, r = 0.98; 4-item, r = 0.929). Mean SE increased with decreasing number of items administered (full item, SE = 0.31; 12-item, SE = 0.33; 8-item, SE = 0.38; 4-item, SE = 0.49). A precision-based stopping rule (mean SE = 0.5) also strongly correlated with actual ABC scores (r = .941) and optimized the relationship between number of items administrated with precision (mean number of items 4.37, range [4-9]). Conclusions An ABC CAT can determine accurate and precise measures of balance confidence in people with stroke with as few as 4 items. Individuals with lower balance confidence may require a greater number of items (up to 9) and attributed to the LEAPS trial excluding more functionally impaired persons. Impact statement Computerized adaptive testing can drastically reduce the ABC's test administration time while maintaining accuracy and precision. This should greatly enhance clinical utility, facilitating adoption of clinical practice guidelines in stroke rehabilitation. Lay summary If you have had a stroke, your physical therapist will likely test your balance confidence. A computerized adaptive test version of the ABC scale can accurately identify balance with as few as 4 questions, which takes much less time.
Crisis as Catalyst: Crisis in Conversion to Islam Related to Radicalism Intentions

In Western democracies, Muslim converts are overrepresented in Islamist terrorism compared to born-and-raised Muslims. Consequently, researchers have begun to consider how the process of conversion...
Calcium Signaling Silencing in Atrial Fibrillation: Implications for Atrial Sodium Homeostasis.

Atrial fibrillation (AF) is the most common type of cardiac arrhythmia, affecting more than 33 million people worldwide. Despite important advances in therapy, AF’s incidence remains high, and treatment often results in recurrence of the arrhythmia. A better understanding of the cellular and molecular changes that (1) trigger AF and (2) occur after the onset of AF will help to identify novel therapeutic targets. Over the past 20 years, a large body of research has shown that intracellular Ca2+ handling is dramatically altered in AF. While some of these changes are arrhythmogenic, other changes counteract cellular arrhythmogenic mechanisms (Calcium Signaling Silencing). The intracellular Na+ concentration ([Na+])i is a key regulator of intracellular Ca2+ handling in cardiac myocytes. Despite its importance in the regulation of intracellular Ca2+ handling, little is known about [Na+]i, its regulation, and how it might be changed in AF. Previous work suggests that there might be increases in the late component of the atrial Na+ current (INa,L) in AF, suggesting that [Na+]i levels might be high in AF. Indeed, a pharmacological blockade of INa,L has been suggested as a treatment for AF. Here, we review calcium signaling silencing and changes in intracellular Na+ homeostasis during AF. We summarize the proposed arrhythmogenic mechanisms associated with increases in INa,L during AF and discuss the evidence from clinical trials that have tested the pharmacological INa,L blocker ranolazine in the treatment of AF.
Adventures and Misadventures: The Bizarre Story of the Dupetit-Thouars Brothers

The year 1789 passed without a word from La Perouse and without any report of wreckage sighted. As the months went by, the probability of shipwreck had to be recognized within the ministry of the marine; but one could hope for the possibility of survivors ashore on some remote island living in expectation of rescue by compassionate compatriots. The mobilization of any such effort by official Paris during the confused opening months of the Revolution was obviously out of the question, leaving the way open, at least for the moment, for private individuals to take an initiative that was a mixture of audacity and madness. Indeed, their plan, hatched in 1790, proved to be so costly to organize in both money and time that the belated official rescue expedition had finally left port some months before the private venture put out to sea.
Parameterized unit testing with Pex

This hands-on tutorial will teach the principles of Parameterized Unit Testing [5,4] with Pex [2], an automatic test input generator for .NET which performs a systematic program analysis, similar to path bounded model-checking. A parameterized unit test is simply a method that takes parameters, calls the code under test, and states assertions.
Genetic expression of aryl hydrocarbon hydroxylase induction. VI. Control of other aromatic hydrocarbon-inducible mono-oxygenase activities at or near the same genetic locus.

Abstract When mice are administered aromatic hydrocarbons, the induction of aryl hydrocarbon (benzo[ a ]pyrene) hydroxylase, p -nitroanisole O -demethylase, 7-ethoxycoumarin O -deethylase, and 3-methyl-4-methylaminoazobenzene N -demethylase activities—all membrane-bound mono-oxygenases having cytochrome P 450 associated with their active sites—is associated with the same genetic locus or with closely linked loci; we have previously proposed that this genetic region be designated the Ah locus for aromatic hydrocarbon responsiveness. Expression of these four inducible enzyme activities occurs as a single autosomal dominant trait in offspring from a genetic cross between inbred C57BL/6N and DBA/2N mice and from the appropriate backcrosses and intercross. There are no striking differences in relative thermolability or ontogenetic expression among these four closely linked aromatic hydrocarbon-induced mono-oxygenase activities. All four of these microsomal enzyme activities exist in two forms—one predominantly present in control or aromatic hydrocarbon-treated genetically nonresponsive mice and the other predominantly present in aromatic hydrocarbon-treated genetically responsive mice; the latter form is preferentially inhibited in vitro by such compounds as α-naphthoflavone. Whether a single induction-specific protein or a group of induction-specific proteins is associated with the Ah locus remains uncertain. The expression of aminopyrine N -demethylase, d -benzphetamine N -demethylase, NADPH-cytochrome c reductase, and NADPH-cytochrome P 450 reductase activities in aromatic hydrocarbon-treated genetically responsive and nonresponsive mice is not correlated with the Ah locus.
GIS decision model for global replication of hybrid closed-loop renewable energy systems

Larger Geographically isolated populations do not typically have access to primary grid power, and thus rely on generating plants that depend on external supplies of fossil fuels to provide consistent access to power. The application of hybrid closed-loop renewable energy systems can alleviate this dependence and significantly reduce the carbon footprint by reducing the effective combustion byproducts per unit of energy provided. Using case study data, a GIS decision model is presented for determining feasible locations for implementing such a switch, based on successive GIS data layers. Data layers include urban, electrification, geographic topography, soil/ground composition, and wind. Further consideration may exist for investigating constraints on the location choice through the application of restriction layers, including conservation areas, historic sites, etc. The probability density function can then be maximized based on the successive layers as a metric for optimizing or prioritizing initial location choice. The quality of GIS layers with respect to information content for varying international locations directly influences the optimization function in this decision model.
Ideal and Reality

Administrators may hope to save money by reducing staff when the acquisitions process is automated. Some employees may dream of the ergonomic office. In times of limited funding reality approaches neither goal. It means instead a long, difficult transition period, increased work loads, backlogs and limited goals, the attainment of which seems to move ever farther into the future. Nearly two years and less than half way toward ultimate goals, an acquisitions librarian can pause to evaluate where we are, how we got there, what lies ahead and what we wish we had known when we started.
RHIC Performance with Polarized Protons in Run-6

The RHIC polarized proton run (Run‐6) in 2006 started on February 1 and continued for 21 weeks. The Run‐6 included the machine operation at different beam energies and with different orientation of beam polarization at the collision points. The machine operation at 100GeV and 31.2 GeV provided physics data of polarized proton collisions to the STAR, PHENIX and BRAHMS experiments. Record levels of the luminosity (up to 3.5⋅1031 cm−2 s−1 peak) and proton beam polarization (up to 65%) were achieved during the 100GeV operation. The beam polarization was preserved during the acceleration by using Siberian Snakes, based on helical magnets. The polarization orientation at STAR and PHENIX experiments was controlled with helical spin rotators. During different stages of the run the physics data were provided with longitudinal, vertical and horizontal orientations of the beam polarization at the collision points. Total luminosity integrals of 45 pb−1 at 100 GeV and 0.35 pb−1 at 31.2 GeV were delivered to the experiments.
Transmembrane topography of the nicotinic acetylcholine receptor delta subunit.

Current folding models for the nicotinic acetylcholine receptor (AChR) predict either four or five transmembrane segments per subunit. The N-terminus of each subunit is almost certainly extracellular. We have tested folding models by determining biochemically the cellular location of an intermolecular disulfide bridge thought to lie at the delta subunit C-terminus. Dimers of AChR linked through the delta-delta bridge were prepared from Torpedo marmorata and T.californica electric organ. The disulfide's accessibility to hydrophilic reductants was tested in a reconstituted vesicle system. In right-side-out vesicles (greater than 95% ACh binding sites outwards), the bridge was equally accessible whether or not vesicles had been disrupted by freeze--thawing or by detergents. Control experiments based on the rate of reduction of entrapped diphtheria toxin and measurements of radioactive reductant efflux demonstrated that the vesicles provide an adequate permeability barrier. In reconstituted vesicles containing AChR dimers in scrambled orientations, right-side-out dimers were reduced to monomers three times more rapidly than inside-out dimers, consistent with the measured rate of reductant permeation. These observations indicate that in reconstituted vesicles the delta-delta disulfide bridge lies in the same aqueous space as the ACh binding sites. They are most easily reconciled with folding models that propose an even number of transmembrane crossing per subunit.
Role of endoscopy in the investigation of upper gastrointestinal symptoms in HIV-infected patients

Endoscopy plays a pivotal role in the management of patients with the acquired immunodeficiency syndrome (AIDS), because tissue documentation of opportunistic processes is often necessary to establish a definitive diagnosis. With progression of immunodeficiency, endoscopy becomes more important because the predisposition to opportunistic disorders of the gastrointestinal tract is greatly increased. The yield of upper endoscopy in human immunodeficiency virus (HIV)-infected patients is dependent upon the indication for the procedure, including the clinical presentation and the stage of immunodeficiency. Indications for which endoscopy has a high yield include AIDS with esophageal symptoms refractory to empirical antifungal therapy, small bowel biopsy for chronic severe diarrhea and upper gastrointestinal bleeding. Although processes can be identified, a diagnosis is less likely in patients who present with nausea and vomiting or nonspecific abdominal pain. By tailoring the use of endoscopy to the presenting symptoms and CD4 lymphocyte count, the diagnostic benefit can be increased.