cssi/SciSciGPT-SciSciNet huggingface dataset:
Oral quercetin administration transiently protects respiratory function in dystrophin-deficient mice.

Key point PGC-1α pathway activation has been shown to decrease disease severity and can be driven by quercetin. Oral quercetin supplementation protected respiratory function for 4-6 months during a 12 month dosing regimen. This transient protection was probably due to a failure to sustain elevated SIRT1 activity and downstream PGC-1α signalling. Quercetin supplementation may be a beneficial treatment as part of a cocktail provided continued SIRT1 activity elevation is achieved. Abstract Duchenne muscular dystrophy (DMD) impacts 1 : 3500 boys and leads to muscle dysfunction culminating in death due to respiratory or cardiac failure. There is an urgent need for effective therapies with the potential for immediate application for this patient population. Quercetin, a flavonoid with an outstanding safety profile, may provide therapeutic relief to DMD patients as the wait for additional therapies continues. This study evaluated the capacity of orally administered quercetin (0.2%) in 2 month old mdx mice to improve respiratory function and end-point functional and histological outcomes in the diaphragm following 12 months of treatment. Respiratory function was protected for the first 4-6 months of treatment but appeared to become insensitive to quercetin thereafter. Consistent with this, end-point functional measures were decreased and histopathological measures were more severe in dystrophic muscle compared to C57 and similar between control-fed and quercetin-fed mdx mice. To better understand the transient nature of improved respiratory function, we measured PGC-1α pathway activity, which is suggested to be up-regulated by quercetin supplementation. This pathway was largely suppressed in dystrophic muscle compared to healthy muscle, and at the 14 month time point dietary quercetin enrichment did not increase expression of downstream effectors. These data support the efficacy of quercetin as an intervention for DMD in skeletal muscle, and also indicate the development of age-dependent quercetin insensitivity when continued supplementation fails to drive the PGC-1α pathway. Continued study is needed to determine if this is related to disease severity, age or other factors.
Visualization of Criminal Activity in an Urban Population

Alex Breuer, Joshua Hursey, Tonya Stroman & Arvind Verma Indiana UniversityBloomington Abstract Crime is a multi-dimensional and complex activity. In order to understand its nature one has to comprehend not only its spatio-temporal dimensions but also the nature of crime, the victimoffender relationship, the role of guardians and history of similar previous incidents. Visualization of all the dimensions is a formidable task due to the limitations of the present methods. Both for the police department and criminal justice researcher the need to deal with a vast amount of data is a pre-requisite to the task of controlling the crime. This paper presents an interactive visualization technique intended to present the viewer with an accurate and intuitive view of the criminal activity in a cityscape. The technique employs many different visualization elements, which taken together presents a useful methodology to handle the important the associated factors of crime. The paper also describes the software technique and discusses avenues for future investigation.
Political Economy and the Problem of Conduct

Karl Marx insists that nineteenth-century political economy is too enamored of Adam Smith’s invisible hand — not only does the ‘free trader vulgaris’ (1981: 280) build on this turn-of-phrase a substantial ideological apparatus that conceals the real forces that shape political-economic life, he also hides from view the disharmonious character of these forces. For Marx, harmony in exchange is not the result of approbative sociality or the management of circumstance, but is an appearance — merely the ideological surface of an inherently disharmonious set of social relations that fuel the production of commodities and the accumulation of wealth. In Volume I of Capital (1867), Marx (1981: 280) argues that the views, concepts, and standards of political economy are derived from only its most visible dimension — ‘the sphere of circulation or commodity exchange’. From the surface of exchange, political economy appears harmonious — a realm of freedom in which buyers and sellers come together to exchange commodities (including labor-power) by their own free will, equal before the law, and looking only to their own advantage. Within the sphere of circulation, ‘either in accordance with the pre-established harmony of things, or under the auspices of an omniscient providence, they all work together to their mutual advantage, for the common weal, and in the common interest’ (1981: 280). To the harmonizer, the domain of political economy is ‘the exclusive realm of Freedom, Equality, Property and Bentham’ (1981: 280).
Subjective and Logical Approaches

We shall now consider that style of statistical inference called subjectivistic or personalistic or (in a special sense) Bayesian. It is based on a conception of probability altogether different from that underlying the investigations of the previous chapters. It was suggested at one point in the last chapter that there might be difficulty in motivating an agent to follow the recommendations of a minimax policy if he had certain convictions concerning the relative likelihood of the various alternative hypotheses. The subjectivistic approach takes this likelihood, and not long-run frequency or propensity, to be the subject matter of probability. Adopting this technique has profound consequences for the theory of statistical inference.
Science Teachers’ Representations of Classroom Practice in the Process of Formative Assessment Design

Formative assessment has been recognized as an essential element of effective classroom practice; as a result, teachers are increasingly required to create formative assessments for their classrooms. This study examines data drawn from a long-term, site-based professional development program that supported a department of biology teachers in the iterative design and enactment of common formative assessment tools. We analyze teacher conversations to understand how teachers collaborated to design formative assessments. Results indicate that when teachers attended to problems of practice related to teaching evolution, increased transparency in their talk helped build consensus about the design of formative assessment tools. These results highlight the importance of encouraging transparency in teacher dialog when they are engaged in collaborative design of formative assessments.
Teaching Economic Evaluation of Health Promotion Programs

One of the essential functions of public health is evaluating the effectiveness and quality of population-based health services. To do this, health professionals and lawmakers must understand the t...
Imprecision: Limitations to Interpretation of a Large Randomized Clinical Trial.

Randomized controlled trials are viewed as providing gold standard evidence, and the declaratively named PRECISION trial (Prospective Evaluation of Celecoxib Integrated Safety versus Ibuprofen or Naproxen)1 implies the final word on the comparative cardiovascular safety of nonsteroidal anti-inflammatory drugs (NSAIDs). The analgesic efficacy of NSAIDs derives largely from suppressing cyclooxygenase 2 (COX-2)–derived prostaglandins E2 and I2 (prostacyclin), whereas their gastrointestinal adverse effects result from the inhibition of cyclooxygenase 1 (COX-1)–derived gastroduodenal prostaglandins E2 and I2 and COX-1–derived thromboxane A2 in platelets. This prompted the development of NSAIDs engineered to inhibit COX-2 specifically, such as rofecoxib, celecoxib, and valdecoxib. Randomized comparisons, such as VIGOR (Vioxx Gastrointestinal Outcomes Research), comparing rofecoxib and naproxen, showed fewer complicated gastrointestinal events with the COX-2 inhibitors.2 The value of randomized trials was also evident when evidence, first from clinical pharmacology and then from experiments in model systems, predicted that cardiovascular events would complicate COX-2 inhibition of prostaglandin I2 in the vasculature. Evidence consistent with this hypothesis emerged from VIGOR with more serious thromboembolic events with rofecoxib. Definitive evidence of cardiovascular hazard subsequently emerged from 10 placebo-controlled trials of structurally distinct COX-2 inhibitors.2 Last, overview analysis of individual data derived from ≈750 randomized trials3 provided a risk estimate of the magnitude of this hazard from COX-2 inhibitors with a rate ratio (RR) for serious vascular events of 1.37 (95% confidence interval, 1.14–1.66). As mechanistically predicted,2 the RRs for celecoxib (average daily dose, 400 mg) and rofecoxib (average daily dose, 25 mg) were superimposable. By contrast, information on older …
Quantifying Myocardial Contractility Changes Using Ultrasound-Based Shear Wave Elastography

Background Myocardial contractility, a significant determinant of cardiac function, is valuable for diagnosis and evaluation of treatment in cardiovascular disorders including heart failure. Shear wave elasticity imaging (SWEI) is a newly developed ultrasound-based elastographic technique that can directly assess the stiffness of cardiac tissue. The aim of this study was to verify the ability of this technique to quantify contractility changes in the myocardium. Methods In 12 isolated rabbit hearts, SWEI measurements were made of systolic stiffness at five different coronary perfusion pressures from 0 to 92 mm Hg. The changes in coronary perfusion were used to induce acute stepwise reversible changes in cardiac contractility via the Gregg effect. The Gregg effect is the dependency of contractility on coronary perfusion. In four of the hearts, the measurements were repeated after delivery of gadolinium, which is known to block the Gregg effect. Results Systolic stiffness measured by SWEI changed linearly with coronary perfusion pressure, with a slope of 0.27 kPa/mm Hg (mean of 95% CI, R 2 = 0.73). As expected, the change in contractility due to the Gregg effect was blocked by gadolinium, with a significant reduction of the slope to 0.08 kPa/mm Hg. Conclusions SWEI measurements of systolic stiffness provide an index of contractility in the unloaded isolated rabbit heart. Although this study was done under ideal imaging conditions and with nonphysiologic loading conditions, it reinforces the concept that this ultrasound technique has the potential to provide a direct and noninvasive index of cardiac contractility.
Differential correlation for sequencing data.

Several methods have been developed to identify differential correlation (DC) between pairs of molecular features from –omics studies. Most DC methods have only been tested with microarrays and other platforms producing continuous and Gaussian-like data. Sequencing data is in the form of counts, often modeled with a negative binomial distribution making it difficult to apply standard correlation metrics. We have developed an R package for identifying DC called Discordant which uses mixture models for correlations between features and the Expectation Maximization (EM) algorithm for fitting parameters of the mixture model. Several correlation metrics for sequencing data are provided and tested using simulations. Other extensions in the Discordant package include additional modeling for different types of differential correlation, and faster implementation, using a subsampling routine to reduce run-time and address the assumption of independence between molecular feature pairs. With simulations and breast cancer miRNA-Seq and RNA-Seq data, we find that Spearman’s correlation has the best performance among the tested correlation methods for identifying differential correlation. Application of Spearman’s correlation in the Discordant method demonstrated the most power in ROC curves and sensitivity/specificity plots, and improved ability to identify experimentally validated breast cancer miRNA. We also considered including additional types of differential correlation, which showed a slight reduction in power due to the additional parameters that need to be estimated, but more versatility in applications. Finally, subsampling within the EM algorithm considerably decreased run-time with negligible effect on performance. A new method and R package called Discordant is presented for identifying differential correlation with sequencing data. Based on comparisons with different correlation metrics, this study suggests Spearman’s correlation is appropriate for sequencing data, but other correlation metrics are available to the user depending on the application and data type. The Discordant method can also be extended to investigate additional DC types and subsampling with the EM algorithm is now available for reduced run-time. These extensions to the R package make Discordant more robust and versatile for multiple –omics studies.
The Longitudinal Career Experiences of Interdisciplinary Neuroscience PhD Recipients.

ABSTRACTInterest in interdisciplinary programs in science, technology, engineering, and mathematics (STEM)-related fields at the graduate-degree level is widespread across American higher education. Using longitudinal qualitative interviews, this article considers the early career experiences of scholars who hold an interdisciplinary PhD in neuroscience. The scholars were interviewed first as doctoral students and then 6 years later. The findings illustrate the challenges of marketability, professional development, and balancing personal and career demands for interdisciplinary PhD recipients in STEM-related fields.
Muscle contraction induced arterial shear stress increases endothelial nitric oxide synthase phosphorylation in humans

Elevations in brachial artery shear in response to forearm exercise increased endothelial nitric oxide synthase Ser1177 phosphorylation in brachial artery endothelial cells of healthy humans. Our p...
Recombinant Synthesis of Hybrid Lipid-Peptide Polymer Fusions that Self-Assemble and Encapsulate Hydrophobic Drugs.

Inspired by biohybrid molecules that are synthesized in Nature through post-translational modification (PTM), we have exploited a eukaryotic PTM to recombinantly synthesize lipid-polypeptide hybrid materials. By co-expressing yeast N-myristoyltransferase with an elastin-like polypeptide (ELP) fused to a short recognition sequence in E. coli, we show robust and high-yield modification of the ELP with myristic acid. The ELP's reversible phase behavior is retained upon myristoylation and can be tuned to span a 30-60 °C. Myristoylated ELPs provide a versatile platform for genetically pre-programming self-assembly into micelles of varied size and shape. Their lipid cores can be loaded with hydrophobic small molecules by passive diffusion. Encapsulated doxorubicin and paclitaxel exhibit cytotoxic effects on 4T1 and PC3-luc cells, respectively, with potencies similar to chemically conjugated counterparts, and longer plasma circulation than free drug upon intravenous injection in mice.
Juggling Multiple Bottom Lines: The Interplay of Feedback from Financial and Environmental Goals

Calls for firms to manage their triple bottom line raise the question of how firms respond to multiple performance indicators that are at different organizational levels and potentially interrelati...
The importance of data curation

The long-term value of data can be dramatically affected, for better or worse, by how well those data are curated. Unfortunately, many valuable datasets are poorly curated, which contributes to errors, redundant effort, and obstacles to replication.. This chapter focuses on four primary challenges to data curation: (1) data integration, allowing interoperability across time and across data sources; (2) electronic dissemination, including online tools for data discovery and manipulation; (3) sustainability, including planning for long-run preservation and access, and the creation of persistent identifiers; and (4) metadata, machine-processable structured documentation. Best practices, including use of the standards for metadata, digital object identifiers, and preservation, are also discussed.
Sustained-release amorphous solid dispersions

The use of amorphous solid dispersions (ASD) to overcome poor drug solubility has gained interest in the pharmaceutical industry over the past decade. ASDs are challenging to formulate because they are thermodynamically unstable, and the dispersed drugs tend to recrystallize. Until now, most research on ASDs has focused on immediate-release formulations, supersaturation, and stability; only a few studies have recently reported on the manufacturing of sustained-release ASDs. Sustained-release ASDs can minimize the frequency of administration and prevent high concentrations that can lead to toxicity. Sustained-release ASDs can also decrease the reprecipitation rate in the medium, which can lead to increased bioavailability. However, sustained-release ASDs also pose some significant challenges, such as intramatrix recrystallization, inhibition of drug release as a result of drug-polymer gelling, and low supersaturation due to a slow dissolution rate. This review details the challenges and the formulation approaches that have been investigated to manufacture sustained-release ASDs. In particular, the advantages and drawbacks of hydrophilic polymers, hydrophobic polymers, and lipid-based systems are discussed.
Managing Client Portfolio in a Two-Tier Supply Chain

Suppliers in a variety of industries today face the challenge of managing their business where the utilization of their capacities fluctuates dramatically over time. The fluctuations can be attributed to the business cycle of the economy, as well as to the amplification of demand variability as one moves upstream (i.e., the bullwhip effect). In this chapter, we investigate the source of the fluctuations by analyzing a two-tier supply chain where the supplier serves many clients whose demands are subject to individual trends and the business cycle of the general economy. We present conditions under which the bullwhip effect or the stabilizing effect of the clients’ orders is felt by the supplier. We also analyze how the supplier can build an efficient client portfolio by analyzing the impact of a new client on the expected profit to the supplier in a newsvendor setting. We derive the key performance indicators that can guide a supplier in the right direction of the client portfolio. Thus, by understanding the clients’ ordering behaviors and its impact on capacity decisions, the supplier can strategically select an efficient client portfolio, so that the risk-neutral supplier would maximize the expected long-term profit.
Basic fibroblast growth factor stimulates myelopoiesis in long-term human bone marrow cultures

We previously showed that basic fibroblast growth factor (bFGF) is a potent mitogen for human bone marrow (BM) stromal cells and significantly delays their senescence. In the present study, we demonstrated that low concentrations of bFGF (0.2 to 2 ng/mL) enhance myelopoiesis in long-term human BM culture. Addition of bFGF to long-term BM cultures resulted in an increase in (a) the number of nonadherent cells (sixfold), particularly those of the neutrophil granulocyte series; (b) the number of nonadherent granulocyte colony-stimulating factor (G-CSF)- and granulocyte-macrophage colony-stimulating factor (GM-CSF)-responsive progenitor cells; (c) the number of adherent foci of hematopoietic cells (10-fold); and (d) the number of progenitor cells in the adherent stromal cell layer. These effects were not noted with higher concentrations of bFGF (20 ng/mL). Thus, low concentrations of bFGF effectively augment myelopoiesis in human long-term BM cultures, and bFGF may therefore be a regulator of the hematopoietic system in vitro and in vivo.
Novel techniques for data warehousing and online analytical processing in emerging applications

A data warehouse is a collection of data for supporting of decision making process. Data cubes and on-line analytical processing (OLAP) have become very popular techniques to help users analyze data in a warehouse. Even though previous studies on a data warehouse and data cube have been proposed and developed, as new applications emerging, there are still technical challenges which have not been addressed well. We propose effective and efficient solutions to the challenging problems in the areas of (1) mining iceberg cube from multiple tables, (2) online answering ad-hoc aggregate queries on data streams, and (3) warehousing pattern-based clusters. Firstly, we argue that the materialized base table assumption in most of the previous studies on computing iceberg cubes is often infeasible in practice. Instead, a data warehouse is often organized with multiple tables in schemas such as star schema, snowflake schema, and constellation schema. We propose a novel approach to compute an iceberg cube from multiple tables in a data warehouse in order to avoid costly materialization of a base table. Secondly, it is infeasible to compute a full data cube for answering ad-hoc aggregate queries on data streams due to a rapid data input and the huge size of data. We develop a new method to answer online ad-hoc aggregate queries on data streams, which is to maintain and index a small subset of aggregate cells on a designed data structure. Last, we extend the data warehousing and OLAP techniques to tackle pattern-based clusters. We propose an efficient method to construct a data warehouse of non-redundant pattern-based clusters.
Zeolitic imidazolate framework membranes made by ligand-induced permselectivation

Zeolitic imidazolate framework (ZIF) membranes are emerging as a promising energy-efficient separation technology. However, their reliable and scalable manufacturing remains a challenge. We demonstrate the fabrication of ZIF nanocomposite membranes by means of an all-vapor-phase processing method based on atomic layer deposition (ALD) of ZnO in a porous support followed by ligand-vapor treatment. After ALD, the obtained nanocomposite exhibits low flux and is not selective, whereas after ligand-vapor (2-methylimidazole) treatment, it is partially transformed to ZIF and shows stable performance with high mixture separation factor for propylene over propane (an energy-intensive high-volume separation) and high propylene flux. Membrane synthesis through ligand-induced permselectivation of a nonselective and impermeable deposit is shown to be simple and highly reproducible and holds promise for scalability.
Monotonic and cyclic simple shear response of gravel-sand mixtures

Abstract Understanding the factors that affect the monotonic and cyclic response of gravelly soils during earthquake events is critical to infrastructure design. In this study a large-size Cyclic Simple Shear (CSS) device was utilized to perform monotonic and cyclic shear tests on mixtures of either subrounded 9 mm Pea Gravel or angular 8 mm Crushed Limestone (CLS8) with subrounded Ottawa C109 sand. Tests were performed in constant volume conditions and shear wave velocity was measured for each specimen. Monotonic and cyclic test results at Dr = 47% show that there is an optimum mixture percentage that results in the greatest shear strength and resistance to liquefaction (40% Sand for Pea Gravel Mixtures and 60% Sand for CLS8 Mixtures). The effects of particle angularity, cyclic stress ratio, and initial vertical stress on monotonic and cyclic response of loose and dense gravel mixtures were investigated and are presented. Comparison of the results from the cyclic simple shear tests with existing liquefaction triggering charts suggests the need for improved charts for gravelly soil liquefaction evaluation.
Broad Environmental Tolerance for a Salicola Host-Phage Pair Isolated from the Cargill Solar Saltworks, Newark, CA, USA.

Phages greatly influence the ecology and evolution of their bacterial hosts; however, compared to hosts, a relatively low number of phages, especially halophilic phages, have been studied. This study describes a comparative investigation of physicochemical tolerance between a strain of the halophilic bacterium, Salicola, isolated from the Cargill Saltworks (Newark, CA, USA) and its associated phage. The host grew in media between pH 6–8.5, had a salinity growth optimum of 20% total salts (ranging from 10%–30%) and an upper temperature growth limit of 48 °C. The host utilized 61 of 190 substrates tested using BIOLOG Phenotype MicroArrays. The CGφ29 phage, one of only four reported Salicola phages, is a DNA virus of the Siphoviridae family. Overall, the phage tolerated a broader range of environmental conditions than its host (salinity 0–30% total salts; pH 3–9; upper thermal limit 80 °C) and is the most thermotolerant halophilic phage ever reported. This study is the most comprehensive investigation to date of a Salicola host–phage pair and provides novel insights into extreme environmental tolerances among bacteriophages.
Climate vulnerability assessment for Pacific salmon and steelhead in the California Current Large Marine Ecosystem

Major ecological realignments are already occurring in response to climate change. To be successful, conservation strategies now need to account for geographical patterns in traits sensitive to climate change, as well as climate threats to species-level diversity. As part of an effort to provide such information, we conducted a climate vulnerability assessment that included all anadromous Pacific salmon and steelhead (Oncorhynchus spp.) population units listed under the U.S. Endangered Species Act. Using an expert-based scoring system, we ranked 20 attributes for the 28 listed units and 5 additional units. Attributes captured biological sensitivity, or the strength of linkages between each listing unit and the present climate; climate exposure, or the magnitude of projected change in local environmental conditions; and adaptive capacity, or the ability to modify phenotypes to cope with new climatic conditions. Each listing unit was then assigned one of four vulnerability categories. Units ranked most vulnerable overall were Chinook (O. tshawytscha) in the California Central Valley, coho (O. kisutch) in California and southern Oregon, sockeye (O. nerka) in the Snake River Basin, and spring-run Chinook in the interior Columbia and Willamette River Basins. We identified units with similar vulnerability profiles using a hierarchical cluster analysis. Life history characteristics, especially freshwater and estuary residence times, interplayed with gradations in exposure from south to north and from coastal to interior regions to generate landscape-level patterns within each species. Nearly all listing units faced high exposures to projected increases in stream temperature, sea surface temperature, and ocean acidification, but other aspects of exposure peaked in particular regions. Anthropogenic factors, especially migration barriers, habitat degradation, and hatchery influence, have reduced the adaptive capacity of most steelhead and salmon populations. Enhancing adaptive capacity is essential to mitigate for the increasing threat of climate change. Collectively, these results provide a framework to support recovery planning that considers climate impacts on the majority of West Coast anadromous salmonids.
Rapid Prototyping 3D Model in Treatment of Pediatric Hip Dysplasia: A Case Report

Background Rapid prototyping is an emerging technology that integrates common medical imaging with specialized production mechanisms to create detailed anatomic replicas. 3D-printed models of musculoskeletal anatomy have already proven useful in orthopedics and their applications continue to expand. Case description We present the case of a 10 year-old female with Down syndrome and left acetabular dysplasia and chronic hip instability who underwent periacetabular osteotomy. A rapid prototyping 3D model was created to better understand the anatomy, counsel the family about the problem and the surgical procedure, as well as guide surgical technique. The intricate detail and size match of the model with the patient's anatomy offered unparalleled, hands-on experience with the patient's anatomy pre-operatively and improved surgical precision. Conclusions Our experience with rapid prototyping confirmed its ability to enhance orthopedic care by improving the surgeon's ability to understand complex anatomy. Additionally, we report a new application utilizing intraoperative fluoroscopic comparison of the model and patient to ensure surgical precision and minimize the risk of complications. This technique could be used in other challenging cases. The increasing availability of rapid prototyping welcomes further use in all areas of orthopedics.
Authentic Language Learning through Telecollaboration in Online Courses

We describe the integration of telecollaborative language coaching sessions into an online Spanish program as the unifying thread for asynchronous learning and reflection activities. In survey responses, students reported improved language skills and cultural knowledge, and the ability to apply linguistic skills to “real-life” situations due to their virtual interactions with native speakers. The importance of authentic learning experiences in online language courses and online courses in other disciplines is discussed.
Ethical Considerations for Biotechnology Leaders

Abstract The dynamic world of corporate biotechnology is one of possibility, productivity, and progress. The biotechnology industry exists at the intersections of science, technology, and public policy, and there are successes, failures, and hazards along the way. This chapter introduces ethical issues and dilemmas that are serious questions about what ought to be done, often in situations of uncertainty. Ethical “arguments” make use of judgments, rules, principles, and theories that form a rational response to a set of circumstances in which one must decide the best course of action. In this chapter, I explain some important themes for biotechnology entrepreneurs, including informed consent, ownership of human tissues and cells and derivative products, intellectual property, patenting, and the possibility of biopiracy, to name a few. The biotechnology entrepreneur should be equipped with an understanding of ethics and embrace a broad concept of corporate social responsibility when making decisions that can benefit society and the industry as a whole.
Laryngitis, Tracheitis, Epiglottitis, and Bronchiolitis

A previously healthy 4-year-old female is seen at a local urgent care with 2 days of fever to 104 °F, fatigue, myalgias, runny nose, cough, hoarse voice, and pain with speaking. A nasopharyngeal swab is positive for influenza A virus. She is diagnosed with influenza infection with associated laryngitis and discharged home with supportive care. She slowly improves over the following 2 days. However, on day 5 of illness, her parents bring her to the Emergency Department for recurrence of high fevers and worsening lethargy, cough, and respiratory distress. Vital signs include a temperature of 40 °C, heart rate 150 beats per minute, respiratory rate of 35 breaths per minute, and a blood pressure of 90/50 mmHg. She is ill-appearing and in moderate respiratory distress, with inspiratory stridor and retractions. A dose of nebulized epinephrine is administered immediately for presumed laryngotracheobronchitis without any clinical improvement. The otolaryngology team is emergently consulted and performs an endotracheal intubation for airway stabilization. On laryngoscopy, exudative tracheitis is noted. Samples of the exudates are obtained and sent to the microbiology laboratory for culture. Empiric intravenous antibiotic therapy (vancomycin and ceftriaxone) for bacterial tracheitis are initiated. The bacterial cultures of the tracheal exudates isolate methicillin-susceptible Staphylococcus aureus. Her antibiotic regimen is then de-escalated to intravenous oxacillin.
‘There is a secret in love’: gender, care and HIV management in South Africa

Research within geography and cognate disciplines have worked to demonstrate the important ways care(ing) informs the emotive, bodily and obligatory nature of gendered health. Although acts of care...
A National Perspective of Patellar Instability in Children and Adolescents in the United States: MPFL Reconstruction Is Three Times Higher Than the Incidence of Isolated Lateral Release.

Purpose The objective was to (1) evaluate any recent changes in the United States in the incidences of medial patellofemoral ligament (MPFL) reconstruction and isolated lateral release for patellar instability in children and adolescents, (2) identify concomitant procedures with MPFL, and (3) report national complication rates after MPFL reconstruction with and without concomitant procedures in children and adolescents. Methods A national database was queried for patients aged 5 to 18 years who underwent operative treatment for patellar instability from 2010 to 2018. Inclusion criteria were either an MPFL reconstruction or lateral release for a diagnosis of patellar instability. Concomitant procedures with MPFL reconstruction assessed were tibial tubercle osteotomy, associated arthroscopic procedures, and lateral release. Changes in incidence in MPFL reconstruction, lateral release and concomitant procedures were assessed. The following postoperative complications were assessed: knee stiffness, infection, patella fracture, and growth arrest or angular deformity. Results 2,161 patients who underwent MPFL reconstruction and 1,159 patients who underwent isolated lateral release for patellar instability were identified. The incidence of MPFL reconstruction in adolescents from 2010 to 2018 did not change significantly (2010: 7.11, 2018: 5.91, P = .137), while isolated lateral release decreased (2010: 6.06, 2018: 1.83, P Conclusions The incidence of MPFL reconstruction remained high from 2010 to 2018, while isolated lateral release decreased during the same time period. Complications after MPFL reconstruction, isolated lateral release, and concomitant procedures were infrequent, with postoperative patella fracture the most common. Level of Evidence IV, case series
Empire of Difference: The Ottomans in Comparative Perspective

This book is a comparative study of imperial organization and longevity that assesses Ottoman successes as well as failures against those of other empires with similar characteristics. Barkey examines the Ottoman Empire's social organization and mechanisms of rule at key moments of its history, emergence, imperial institutionalization, remodeling, and transition to nation-state, revealing how the empire managed these moments, adapted, and averted crises and what changes made it transform dramatically. The flexible techniques by which the Ottomans maintained their legitimacy, the cooperation of their diverse elites both at the center and in the provinces, as well as their control over economic and human resources were responsible for the longevity of this particular 'negotiated empire'. Her analysis illuminates topics that include imperial governance, imperial institutions, imperial diversity and multiculturalism, the manner in which dissent is handled and/or internalized, and the nature of state society negotiations.
Evolution and the Structure of Worldview Change

As we know, as life changes ideology and worldview can change, although many times not. Receptivity toward evolution can follow suit. Respective of the recent move in science educational research to consider worldview, this chapter illustrates stark examples of students’ worlds in flux, and the terms by which conceptions of science change. I present three case studies that show how ideology and commitment toward evolution changes when one’s worldview is rearranged by the contingency of social life. In each of these cases, it was by dramatic upheaval or constant tension outside of the influence of science education. For two students, moving one’s position toward evolution required quite dramatic ontological shifts. For a third, maintaining an inclusivist view requires negotiating diametrically opposed perspectives within their immediate social life.
Endogenous Parkin Preserves Dopaminergic Substantia Nigral Neurons following Mitochondrial DNA Mutagenic Stress

Parkinson's disease (PD) is a neurodegenerative disease caused by the loss of dopaminergic neurons in the substantia nigra. PARK2 mutations cause early-onset forms of PD. PARK2 encodes an E3 ubiquitin ligase, Parkin, that can selectively translocate to dysfunctional mitochondria to promote their removal by autophagy. However, Parkin knockout (KO) mice do not display signs of neurodegeneration. To assess Parkin function in vivo, we utilized a mouse model that accumulates dysfunctional mitochondria caused by an accelerated generation of mtDNA mutations (Mutator mice). In the absence of Parkin, dopaminergic neurons in Mutator mice degenerated causing an L-DOPA reversible motor deficit. Other neuronal populations were unaffected. Phosphorylated ubiquitin was increased in the brains of Mutator mice, indicating PINK1-Parkin activation. Parkin loss caused mitochondrial dysfunction and affected the pathogenicity but not the levels of mtDNA somatic mutations. A systemic loss of Parkin synergizes with mitochondrial dysfunction causing dopaminergic neuron death modeling PD pathogenic processes.
On the existence of weakest failure detectors for mutual exclusion and k-exclusion

Research over the past two decades has identified the weakest failure detectors for several important problems in fault-tolerant distributed computing. A recent work has shown that, for a certain definition of the term "problem," every problem that is solvable using failure detectors has a weakest failure detector. In sharp contrast to these results, we prove that a fundamental problem in concurrent computing--FCFS Mutual Exclusion--is solvable using failure detectors, but has no weakest failure detector in the shared memory model. To the best of our knowledge, this is the first problem that is proved not to have a weakest failure detector. We also show that, if the FCFS requirement is dropped, the mutual exclusion problem has a weakest failure detector. In fact, we present the weakest failure detector for the more general problem of starvation-free k-exclusion, for any k.
Bilateral scrotal extramammary Paget's disease in a Chinese man.

A 67-year-old Chinese physician was seen for an eruption on his right scrotum, of several months’ duration. He complained of mild intermittent pruritus, but denied pain or other symptoms. The patient had a past history of extramammary Paget's disease (EMPD) involving the left side of his scrotum 12 years ago. The left scrotal lesion was excised en bloc. The histopathology confirmed that the margins were free of tumor. Periodic acid Schiff (PAS) and carcinoembryonic antigen (CEA) stains were positive, consistent with the diagnosis of EMPD. An evaluation for underlying gastrointestinal and urogenital neoplasia was negative. He continues to have annual examinations, including colonoscopy and prostate-specific antigen study, which have all been negative.
Decision-Centric Information Monitoring

We are interested in information management for decision support applications, especially those that monitor distributed, heterogeneous databases to assess time-critical decisions. Users of such applications can easily be overwhelmed with data that may change rapidly, may conflict, and may be redundant. Developers are faced with a dilemma: either filter out most information and risk excluding critical items, or gather possibly irrelevant or redundant information, and overwhelm the decision maker. This paper describes a solution to this dilemma called decision-centric information monitoring (DCIM). First, we observe that decision support systems should monitor only information that can potentially change some decision. We present an architecture for DCIM that meets the requirements implied by this observation. We describe techniques for identifying the highest value information to monitor and techniques for monitoring that information despite autonomy, distribution, and heterogeneity of data sources. Finally, we present lessons learned from building LOOKOUT, which is to our knowledge the first implementation of a top-to-bottom system performing decision-centric information monitoring.
Synthesis of poly(phosphonylhydrazides)

Phenylphosphonic diisocyanate has been prepared and polymers from its condensation with hydrazines using the interfacial technique are reported. The polymers are believed to contain the following repeating structure: Die Grenzflachenpolykondensation von Phenylphosphonsaurediisocyanaten mit verschiedenen Hydrazinen wird beschrieben. Die Polymeren haben wahrscheinlich die folgende Struktur:
Tissue time course and bioavailability of the pyrethroid insecticide bifenthrin in the Long-Evans rat

1. Pyrethroids are neurotoxic and parent pyrethroid appears to be toxic entity. This study evaluated the oral disposition and bioavailability of bifenthrin in the adult male Long-Evans rat. 2. In the disposition study, rats were administered bifenthrin (0.3 or 3 mg/kg) by oral gavage and serially sacrificed (0.25 h to 21 days). Blood, liver, brain and adipose tissue were removed. In the bioavailability study, blood was collected serially from jugular vein cannulated rats (0.25 to 24 h) following oral (0.3 or 3 mg/kg) or intravenous (0.3 mg/kg) administration of bifenthrin. Tissues were extracted and analyzed for bifenthrin by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). 3. Bifenthrin concentration in blood and liver peaked 1-2-h postoral administration and were approximately 90 ng/ml (or g) and 1000 ng/ml (or g) for both tissues at 0.3 and 3 mg/kg, respectively. Bifenthrin was rapidly cleared from both blood and liver. Brain concentrations peaked at 4-6 h and were lower than in blood at both doses (12 and 143 ng/g). Bifenthrin in adipose tissue peaked at the collected time points of 8 (157 ng/g) and 24 (1145 ng/g) h for the 0.3 and 3 mg/kg doses, respectively and was retained 21 days postoral administration. Following intravenous administration, the blood bifenthrin concentration decreased bi-exponentially, with a distribution half-life of 0.2 h and an elimination half-life of 8 h. Bifenthrin bioavailability was approximately 30%. These disposition and kinetic bifenthrin data may decrease uncertainties in the risk assessment for this pyrethroid insecticide.
Adaptable object request brokers for information survivability of evolvable real-time command and control systems

This paper describes an approach to building adaptable and evolvable real-time command and control (C2) systems. In particular, it presents an overview of the Evolvable and Adaptable Real-Time Distributed Object Management projects carried out at the MITRE Corporation and then discusses information survivability aspects for such systems. In particular issues on integrating security, real-time and fault tolerance requirements are discussed.
Vesicle dynamics in uniform electric fields: squaring and breathing.

We computationally investigate the dynamics of a vesicle exposed to uniform DC or AC electric fields. We employ the two-dimensional boundary integral method in order to simulate vesicle deformation under experimental conditions where peculiar drum-like (“squared”) shapes have been observed. The vesicle membrane is modeled as an infinitely thin, capacitive, area-incompressible interface, with the surrounding fluids acting as leaky dielectrics. Our simulations capture the “squaring” phenomenon, in which vesicles deform into rectangular profiles with corner-like regions of high curvature, as vesicles undergo dynamic transitions between oblate and prolate ellipsoidal shapes.
Epitaxy and misfit dislocations in large misfit systems

Abstract The manner in which an epitaxial overgrowth is accommodated to a substrate composed of a different material depends on such factors as the surface and interfacial energies and the lattice misfit. The former tends to control the growth mode whilst the latter is an important factor in determining the magnitude and presence of elastic strain and misfit dislocations. In small misfit systems the overgrowth tends to be pseudomorphic with the substrate up to a critical thickness beyond which the elastic strain decreases as the misfit dislocation density increases. In large misfit systems pseudomorphism does not occur because the critical thickness is less than a monolayer. Also the expected misfit dislocation spacing is less than that which can be resolved by conventional transmission electron microscopy. Experimental results, however, indicate relatively widely spaced dislocations with average spacings that are weakly if at all dependent on the overgrowth thickness. By contrast the elastic strains decrease in the expected manner as the film thickens. The inadequacy of the conventional lattice misfit theory in large misfit systems is not surprising because in this case one of the basic assumptions of the theory is violated,i.e. small areas of poor fit are not separated by large areas of good fit. In fact essentially the whole interface consists largely of regions of poor fit. For this reason it has been suggested that the coincidence lattice misfit theory may be more usefully applied to the growing bilayer in a manner analogous to the natural lattice misfit theory used for small misfit systems. Recent experimental results on various systems using smooth (111) face-centered cubic metal substrates have lent substantial support to this view.
Tumor necrosis factor‐alpha (TNF‐α) regulates Toll‐like receptor 2 (TLR2) expression in microglia

Microglia represent one effector arm of CNS innate immunity as evident by their role in pathogen recognition. We previously reported that exposure of microglia to Staphylococcus aureus (S. aureus), a prevalent CNS pathogen, led to elevated Toll-like receptor 2 (TLR2) expression, a pattern recognition receptor capable of recognizing conserved structural motifs associated with gram-positive bacteria such as S. aureus. In this study, we demonstrate that the proinflammatory cytokine tumor necrosis factor-α (TNF-α) enhances TLR2 expression in microglia, whereas interleukin-1β has no significant effect. To determine the downstream signaling events responsible for elevated microglial TLR2 expression in response to TNF-α, a series of signal transduction inhibitors were employed. Treatment with caffeic acid phenethyl ester, an inhibitor of redox-mediated nuclear factor-kappa B activation, significantly attenuated TNF-α-induced TLR2 expression. Similar results were observed with the IKK-2 and IκB-α inhibitors SC-514 and BAY 11-7082, respectively. In contrast, no significant alterations in TLR2 expression were observed with protein kinase C or p38 mitogen-activated protein kinase inhibitors. A definitive role for TNF-α was demonstrated by the inability of S. aureus to augment TLR2 expression in microglia isolated from TNF-α knockout mice. In addition, TLR2 expression was significantly attenuated in brain abscesses of TNF-α knockout mice. Collectively, these results indicate that in response to S. aureus, TNF-α acts in an autocrine/paracrine manner to enhance TLR2 expression in microglia and that this effect is mediated, in part, by activation of the nuclear factor-kappa B pathway.
Prediction of the secondary structure of mouse nerve growth factor and its comparison with insulin.

Abstract Five secondary structure prediction methods based on amino acid sequence have been used to predict the secondary structure of mouse nerve growth factor (NGF). The regions predicted helical do not correlate well with the proposal, based on the alignment of primary sequences, that the NGF peptide chain is structurally and evolutionarily related to proinsulin.