cssi/SciSciGPT-SciSciNet huggingface dataset:
Quality of life in children three and nine months after discharge from a paediatric intensive care unit: a prospective cohort study

Improved survival in children with critical illnesses has led to new disease patterns. As a consequence evaluation of the well being of survivors of Pediatric Intensive Care Units (PICU) has become important. Outcome assessment should therefore consist of evaluation of morbidity, functional health and Health Related Quality of Life (HRQoL). Awareness of HRQoL consequences and physical sequelae could lead to changes in support during the acute phase and thereafter. The aim of this study was to evaluate HRQoL in PICU survivors. Prospective follow-up study three and nine months after discharge from a 14-bed tertiary PICU. Eighty-one of 142 eligible, previously healthy children were included from December 2002 through October 2005. HRQoL was assessed with the TNO-AZL Preschool Children Quality of Life Questionnaire (TAPQOL-PF) for children aged 1 to 6 years of age, the TNO-AZL Children's Quality of Life Questionnaire Parent Form (TACQOL-PF) for children aged 6 to 12 years of age, and the TNO-AZL Children's Quality of Life Questionnaire Child Form (TACQOL-CF) for children aged 8 to 15 years of age. The studied patients were compared with age appropriate normative data using non-parametric tests and effect sizes. Thirty-one and 27 children, and 55 and 50 parents completed questionnaires respectively three and nine months after discharge. In 1–6 year old children parents reported more lung problems (3 and 9 months), worse liveliness (9 months) and better appetite and problem behaviour (3 months); in 6–12 year old children parents reported worse motor functioning (3 months); and 12–15 year old adolescents reported worse motor functioning (3 months). Large effect sizes indicating clinical significant differences in HRQoL with healthy control subjects were found on more domains. In this small group of PICU survivors differences in HRQoL with the normative population exist three and nine months after discharge. Calculated effect sizes were smaller nine months after discharge. These changes suggest that HRQoL improves over time. More research is necessary but we believe that HRQoL assessment should be incorporated in follow-up programs of PICU survivors.
Automated Microarray Image Analysis Toolbox for MATLAB

Summary: The Automated Microarray Image Analysis (AMIA) Toolbox for MATLAB is a flexible, open-source, microarray image analysis tool that allows the user to customize analyses of microarray image sets. This tool provides several methods to identify and quantify spot statistics, as well as extensive diagnostic statistics and images to evaluate data quality and array processing. The open, modular nature of AMIA provides access to implementation details and encourages modification and extension of AMIA's capabilities. Availability: The AMIA Toolbox is freely available at http://www.pnl.gov/statistics/amia. The AMIA Toolbox requires MATLAB 6.5 (R13) (MathWorks, Inc. Natick, MA), as well as the Statistics Toolbox 4.1 and Image Processing Toolbox 4.1 for MATLAB or more recentversions. Contact: amanda.white@pnl.gov
Local government IT implementation issues: a challenge for public administration

This paper addresses the issues affecting information technology development and deployment. The issues represented are addressed in the context of IT implementation processes, especially with regard to the question of the needs and perceptions of administrators from the local government arena.. This paper provides two primary results. The first is that strategic planning for IT is fundamental to the ultimate effectiveness of IT implementation. Secondly, it is shown that the expertise levels of executives with regard to IT has proven to be a contributing factor to effectiveness of the IT development and deployment process.
CACTI-FinFET: an integrated delay and power modeling framework for FinFET-based caches under process variations

We present CACTI-FinFET, an integrated framework for simulation of power, delay, temperature, as well as process variations of FinFET-based caches. We have developed a FinFET design library and process variation models to characterize the delay and leakage spreads of such caches. We present results for various FinFET design styles and show that mixing different design styles may be a promising strategy for optimizing cache delay and leakage.
Rural School Vehicle Routing Problem

The school bus routing problem traditionally has been defined in an urban context. However, because of the unique attributes of the problem in rural areas, traditional heuristic methods for solving the problem may produce impractical results. In many cases, these characteristics also provide the opportunity to investigate what size and mix of vehicles, whether large or small buses, conforming vans, or other modes, are most efficient. In addition, these vehicles may be further differentiated by the presence of equipment for transporting students with special needs. To address this situation, a mathematical model of the problem was constructed and a new heuristic was developed. This heuristic consists of two parts: constructing the initial route and then improving it by using a fixed tenure tabu search algorithm. This rural routing heuristic, in addition to several existing ones, is then applied to a randomly generated school district with rural characteristics. For the relevant measure, a function of stude...
Transient coupling reduction and design considerations in edge-coupled coplanar waveguide couplers

Edge-coupled coplanar waveguide (CPW) forward directional couplers are studied using an even/odd mode analysis. Specific height combinations of multilayer substrates are found which equalize the phase velocities of the even and odd modes. These modal velocity equalization points are seen to be relatively constant over a wide band of frequencies. Results of simulated pulse distortion are presented in a multilayer compensated structure showing a dramatic reduction in transient signal coupling and overall distortion. Design considerations for practical circuit designs are also discussed.
Nonperturbative many-body techniques applied to a Yang-Mills field theory.

Starting from the cutoff version of a field-theoretical Hamiltonian derived from an SU(n) Yang-Mills theory in the Coulomb gauge, we investigate the structure of the emerging many-body problem within a Bogoliubov approximation for the ground state ( = physical vacuum) and by considering suitable quasiparticle excitations for glueball states. The idea of the formation of a bag can be incorporated into this scheme. The energy expectation values are approximated by a cluster expansion. The (formal) results, allowing the numerical computation of the glueball spectrum at a later stage, are presented and the emerging structure is discussed. Special attention is hereby paid to the significance of the Gribov ambiguity and to the consequences of the singularity of the Hamiltonian at the Gribov horizon. It is suggested that the possibility of a rising potential between gluons be investigated, as such a potential could be a signal of confinement.
A potent and selective nonpeptide antagonist of the melanocortin-4 receptor induces food intake in satiated mice

Abstract Optimization on a series of piperazinebenzylamines resulted in analogues with low nanomolar binding at the human MC4 receptor but weak affinity (Ki > 500 nM) at the MC3 receptor. Compound 14c was identified to be a potent MC4R antagonist (Ki = 3.2 nM) with a selectivity of 240-fold over MC3R. It proved to be an insurmountable antagonist in a cAMP assay. Compound 14c potently stimulated food intake in satiated mice when given by intracerebroventricular administration.
ACR Appropriateness Criteria® on Advanced Cervical Cancer Expert Panel on Radiation Oncology-Gynecology.

*University of Utah Medical Center, Salt Lake City, UT; yMedical College of Wisconsin, Milwaukee, WI; zUniversity of Texas, M.D. Anderson Cancer Center, Houston, TX; xOhio State Comprehensive Cancer Center-James Cancer Hospital, Columbus, OH; {Long Beach Memorial Medical Center, Long Beach, CA; kIndiana University School of Medicine, Indianapolis, IN; American College of Obstetricians and Gynecologists, Washington, DC; **Tennessee Oncology, Nashville, TN; yyAmerican Society of Clinical Oncology, Alexandria, VA; zzRobert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL; xxUniversity of North Carolina Hospital, Chapel Hill, NC; {{University of Miami, Miami, FL; kkUniversity of California San Diego, San Diego, CA; Ohio State University, Columbus, OH; ***Indiana University Medical Center, Indianapolis, IN
Genome increase as a clock for the origin and evolution of life

Background: The size of non-redundant functional genome can be an indicator of biological complexity of living organisms. Several positive feedback mechanisms including gene cooperation and duplication with subsequent specialization may result in the exponential growth of biological complexity in macro-evolution. Results: I propose a hypothesis that biological complexity increased exponentially during evolution. Regression of the logarithm of functional non-redundant genome size versus time of origin in major groups of organisms showed a 7.8-fold increase per 1 billion years, and hence the increase of complexity can be viewed as a clock of macro-evolution. A strong version of the exponential hypothesis is that the rate of complexity increase in early (pre-prokaryotic) evolution of life was at most the same (or even slower) than observed in the evolution of prokaryotes and eukaryotes. Conclusion: The increase of functional non-redundant genome size in macro-evolution was consistent with the exponential hypothesis. If the strong exponential hypothesis is true, then the origin of life should be dated 10 billion years ago. Thus, the possibility of panspermia as a source of life on earth should be discussed on equal basis with alternative hypotheses of de-novo life origin. Panspermia may be proven if bacteria similar to terrestrial ones are found on other planets or satellites in the solar system.
Variation in the Properties of Superlattices with Band Offsets

The implications for recent reports of large valence band offsets the HgTe-CdTe heterojunction are examined. The variation of the band gap and effective mass for transport normal to the layers in the superlattice is examined in detail.
The Melting Temperature of Liquid Water with the Effective Fragment Potential

The direct simulation of the solid-liquid water interface with the effective fragment potential (EFP) via the constant enthalpy and pressure (NPH) ensemble was used to estimate the melting temperature (T(m)) of ice-I(h). Initial configurations and velocities, taken from equilibrated constant pressure and temperature (NPT) simulations at P = 1 atm and T = 305 K, 325 K and 399 K, respectively, yielded corresponding T(m) values of 378 ± 16 K, 382 ± 14 K and 384 ± 15 K. These estimates are consistently higher than experiment, albeit to the same degree as previously reported estimates using density functional theory (DFT)-based Born-Oppenheimer simulations with the Becke-Lee-Yang-Parr functional plus dispersion corrections (BLYP-D).
Efficient evaluation of xml queries

The contributions in this thesis focus on processing XML queries using an algebra and on exploiting optimization opportunities to enhance execution performance. Algebraic native XQuery implementation has focused on efficient evaluation of XPath expressions. However, little has been done on efficient evaluation of queries as a whole. As our first contribution, we introduce the Generalized Tree Pattern (GTP) as a concise representation of XQueries. Evaluating the query reduces to finding matches for its GTP. Using this idea we develop efficient evaluation plans that significantly outperform the competition. A bulk algebra requires manipulation of sets of objects that are structurally homogeneous; but this statement is in contrast with the nature of XML query processing. We address this problem with the introduction of Annotated Pattern Trees and Tree Logical Classes. We show that it is possible to define bulk operations on structurally heterogeneous sets of trees by inducing homogeneity through a tree logical class reduction. We define a Tree Logical Class (TLC) algebra and demonstrate its utility in evaluating XQuery. We show that TLC produces better performing evaluation plans than competing tree algebra techniques. XML and XQuery semantics are order sensitive. The order is determined upon elaborate explicit and implicit parameters. Determining the correct output order, as well as the order of each operator while optimizing the placement of SORTs is a non-trivial procedure that can significantly affect the query evaluation performance. Our solution uses Hybrid Collections annotated with Ordering and Duplicate Specifications. We show how we produce the correct output order while allowing for algebraic rewrites that enhance performance. XML is treated as schema-less to allow for evaluation techniques to be executed in the absence of schema. We assume schema knowledge exists and try to explore using it as a performance enhancing tool. For our last contribution, we show practical structures to store metadata knowledge, the Schema Information Graph (SIG) and the Alternate Paths, and algorithms that take advantage of them within the constraints of an optimizer. Optimized plans are shown to significantly outperform 'naive' ones.
Psychological Co-morbidities of COPD

Chronic obstructive pulmonary disease (COPD) is a chronic, debilitating disease characterized by airflow limitations that result in significant morbidity and mortality. This chapter will review the pathophysiology of COPD, the prevalence of both the disease and its psychological comorbidities, anxiety, panic disorder, and depression and explore evidence-based treatment options.
Discovery of VX-509 (Decernotinib): A Potent and Selective Janus Kinase 3 Inhibitor for the Treatment of Autoimmune Diseases.

While several therapeutic options exist, the need for more effective, safe, and convenient treatment for a variety of autoimmune diseases persists. Targeting the Janus tyrosine kinases (JAKs), which play essential roles in cell signaling responses and can contribute to aberrant immune function associated with disease, has emerged as a novel and attractive approach for the development of new autoimmune disease therapies. We screened our compound library against JAK3, a key signaling kinase in immune cells, and identified multiple scaffolds showing good inhibitory activity for this kinase. A particular scaffold of interest, the 1H-pyrrolo[2,3-b]pyridine series (7-azaindoles), was selected for further optimization in part on the basis of binding affinity (Ki) as well as on the basis of cellular potency. Optimization of this chemical series led to the identification of VX-509 (decernotinib), a novel, potent, and selective JAK3 inhibitor, which demonstrates good efficacy in vivo in the rat host versus graft mo...
Retinally induced aniseikonia: a case series.

Purpose To report the clinical findings for patients with binocular vision difficulties attributed to retinally induced aniseikonia. Methods Clinical records of patients referred to the author and diagnosed with retinally induced aniseikonia from 2006 to 2012 were retrospectively reviewed. Results Twelve patients with retinally induced aniseikonia attributed to epiretinal membrane, retinal detachment surgical repair, or age-related macular degeneration are reported. Eleven patients were male. The age range was 44 to 76 years. Diplopia occurred in 10 patients, and prism lenses were prescribed for seven patients by their referring practitioner. The amount of aniseikonia measured using either the computerized Aniseikonia Inspector (visual field angle, approximately 14.5 degrees) or the new Aniseikonia test (visual field angle, approximately 5.7 degrees) ranged from 1.7 to 11.3% and from 1.5 to 13.3% in the vertical and horizontal meridians, respectively. At other visual field angles, the amount of aniseikonia might have been different. Five patients perceived macropsia and seven patients perceived micropsia in the affected eye. Seven patients had measurable stereopsis. Use of Bangerter filters was the most frequent treatment modality. Detailed case reports on three patients are included. Conclusions Retinally induced aniseikonia is an increasingly important cause of binocular vision symptoms in the aging population. Long-term studies on its incidence, clinical course, and effect of treatment are needed.
The utility of the aortic dissection team: outcomes and insights after a decade of experience

Background: Mortality rates following acute type A aortic dissection (ATAAD) repair are reduced when operations are performed by a high-volume acute aortic dissection (AAD) team, leading to efforts to centralize ATAAD care. Here, we describe our experience with ATAAD repair by our AAD team over the last 10 years, with a focus on patient selection, transfer protocols, operative approach, and volume trends over time. Methods: An AAD team was implemented at our institution in 2005, with dedicated high-volume AAD surgeons, a multidisciplinary approach to thoracic aortic disease management, and a standardized protocol for ATAAD repair. Further process improvements were made in 2013 to facilitate the rapid transfer of ATAAD patients to our institution using stream-lined triage, diagnostic, and transfer protocols for patients with suspected ATAAD (RACE-AD protocol). Volume trends and outcomes were assessed longitudinally over this period. Results: Institutional ATAAD repair volume remained constant at 12±2 cases per year from 2005–2013, but increased nearly two-fold to 22±6 cases per year (P=0.004) from 2013–2015 following implementation of the RACE-AD protocol. To accommodate this increased volume, two additional surgeons were added to the AAD team. Surgeon ATAAD repair volume was unchanged over the 10-year interval (7.9±3.9 cases per year from 2005–2013 versus 5.5±1.5 cases per year from 2013–2015; P=0.36), and all AAD team surgeons consistently met or exceeded the high-volume surgeon threshold of 5 ATAAD repairs per year. Thirty-day/in-hospital mortality rates of less than 10% were maintained over the study period. Conclusions: Centralization of ATAAD care has begun to occur at our center, with maintenance of low mortality rates for ATAAD repair. These data confirm a net positive impact on regional ATAAD outcomes through transfer of patients to a high-volume center with dedicated AAD surgeons.
Importance of Raman Lidar Aerosol Extinction Measurements for Aerosol-Cloud Interaction Studies

Using a UV Raman Lidar for aerosol extinction, and combining Microwave Radiometer derived Liquid Water Path (LWP) with Multifilter Rotating Shadowband Radiometer derived Cloud Optical depth, to get cloud effective radius (R eff ), we observe under certain specialized conditions, clear signatures of the Twomey Aerosol Indirect effect on cloud droplet properties which are consistent with the theoretical bounds. We also show that the measurement is very sensitive to how far the aerosol layer is from the cloud base and demonstrate that surface PM25 is far less useful. Measurements from both the DOE ARM site and new results at CCNY are presented.
The Effects of Generative Visual Manipulation Strategies within Computer-Based Instruction

AbstractThe purpose of this study was to examine the effectiveness of a generative learning strategy involving learner manipulation of visual elements in computer-based instruction. Distinct from computer-controlled animated visuals, generative manipulation of visuals requires the learner to actively move and place visual elements in an attempt to induce cognitive processing of the content. Stratified random sampling based on prior knowledge of 184 subjects was used to assign students to three treatment groups representing two forms of learner-directed generative visual manipulation and one form of computer-controlled visual manipulation as well as a control. Results and conclusions are presented below.
Stability of Brillouin flow in the presence of slow-wave structure

Including a slow-wave structure (SWS) on the anode in the conventional, planar, and inverted magnetron, we systematically study the linear stability of Brillouin flow, which is the prevalent flow in crossed-field devices. The analytic treatment is fully relativistic and fully electromagnetic, and it incorporates the equilibrium density profile, flow profile, and electric field and magnetic field profiles in the linear stability analysis. Using parameters similar to the University of Michigan's recirculating planar magnetron, the numerical data show that the resonant interaction of the vacuum circuit mode and the corresponding smooth-bore diocotron-like mode is the dominant cause for instability. This resonant interaction is far more important than the intrinsic negative (positive) mass property of electrons in the inverted (conventional) magnetron geometry. It is absent in either the smooth-bore magnetron or under the electrostatic assumption, one or both of which was almost always adopted in prior analyt...
Developing an indicator for fatigue cracking in hot mix asphalt pavements using viscoelastic continuum damage principles

Fatigue cracking in asphalt pavements results in decreased ride quality, decreased fuel economy, and provides an avenue for intrusion of water. Design of the mixture is predominantly focused on volumetrically balancing the amount of air, asphalt, and aggregate in the system. Such an approach only implicitly considers performance and so the natural progression is to design through direct material property assessment and correlations to field performance. The objectives of this paper are to relate mixture stiffness, fatigue, and pavement system characteristics together for use in performance-based mixture design; identify a Simplified-Viscoelastic Continuum Damage model output parameter which produces the most separation between poorly and satisfactorily performing structures when combined with dynamic modulus and phase angle information; and evaluate the impact of reclaimed asphalt pavement on the performance of the indicator. Results show a relationship between fatigue life of the pavement system and an energy-based index. This approach holds promise because of its reliance on material attributes that can be derived on one testing machine. The constitutive model parameters can be found from the direct tension cyclic fatigue test and can be incorporated into prediction software, further enhancing the appeal of a performance specification.
The Effect of HIV-Centered Obstetric Care on Perinatal Outcomes Among a Cohort of Women Living With HIV

BACKGROUND Elimination of perinatal transmission is possible but limited by missed care opportunities. Our objective was to investigate the effects of HIV-centered obstetric care (HCC) on missed care opportunities and perinatal HIV transmission in 2 obstetric cohorts at our institution from 2000 to 2014. METHODS This was a retrospective cohort study of HIV-exposed mother-infant pairs delivering from 2000 to 2014, analyzed according to SQUIRE 2.0 (Standards for Quality Improvement Reporting Excellence) guidelines. Before 2009, women received care in high-risk obstetric care (HRC); subsequently, an HCC service was established. Women who received HRC vs HCC obstetric care were compared to determine differences in maternal and neonatal outcomes. Continuous variables were compared with Student t test and Wilcoxon rank sum tests. Categorical variables were compared using χ test and Fisher exact test. Logistic regression analyses were performed to determine factors associated with outcomes of interest. RESULTS Over 14 years, 161 women delivered 217 HIV-exposed infants; 78 (36%) women received HCC. Two perinatal HIV transmissions (1.5%) occurred in HRC group compared with none in the HCC group (P = 0.3). Women in HCC were more likely to have HIV RNA viral load <1000 copies per milliliter at delivery (12% vs 26%, P = 0.02), have a contraception plan before delivery (93% vs 60%, P < 0.001), return for postpartum evaluation (80% vs 63%, P = 0.01), and have undetectable HIV viral load postpartum (50 copies per milliliter vs 2067, P < 0.0001). CONCLUSIONS HCC can potentially reduce the risk of perinatal HIV transmission by improving maternal virologic control during pregnancy and postpartum and increasing postpartum contraceptive use.
Detoxification of Fusaric Acid by the Soil Microbe Mucor rouxii.

Fusarium oxysporum f. sp. vasinfectum race 4 (VCG0114), which causes root rot and wilt of cotton (Gossypium hirsutum and G. barbadense), has been identified recently for the first time in the western hemisphere in certain fields in the San Joaquin Valley of California. This pathotype produces copious quantities of the plant toxin fusaric acid (5-butyl-2-pyridinecarboxylic acid) compared to other isolates of F. oxysporum f. sp. vasinfectum (Fov) that are indigenous to the United States. Fusaric acid is toxic to cotton plants and may help the pathogen compete with other microbes in the soil. We found that a laboratory strain of the fungus Mucor rouxii converts fusaric acid into a newly identified compound, 8-hydroxyfusaric acid. The latter compound is significantly less phytotoxic to cotton than the parent compound. On the basis of bioassays of hydroxylated analogues of fusaric acid, hydroxylation of the butyl side chain of fusaric acid may affect a general detoxification of fusaric acid. Genes that control...
The dispersion and differentiation of the transplanted adult neuronal percursors in the adult striatum

P224 The neuronal precursors persist in the adult subventricular zone (SVZ) and they may also be present in the adult rostral migratory stream (RMS). In the present study, we examined whether the cells derived from the adult SVZ and RMS can survive and retain their ability to migrate and differentiate into neurons when they are transplanted into adult brain. Donor cells were harvested from the SVZ and RMS in the adult Wistar rats and were cultured for ten days before transplantation. To distinguish donor cells from those of the host after transplantation, the donor cells were labeled with bromodeoxyuridine (BrdU). The BrdU labeled donor cells were transplanted into the cortex and striatum of the adult male Wistar rats (n=16). The rats were sacrificed at 7 days (n=8) and 28 days (n=8) after transplantation. Grafted cells were present within the recipient regions in the rats sacrificed 7days after transplantation. However, 28 days after transplantation the BrdU labeled cells derived from both the SVZ and RMS migrated extensively from their implantation site a radial distance of approximately 2 mm in the striatum but not in the cortex. Double immuofluorescent staining revealed that 65% of grafted cells were neurons (both BrdU and MAP2 immunoreactive) and 20% were astrocytes (both BrdU and GFAP immunoreactive). Our data demonstrate that the transplanted adult neuronal precursors from both the SVZ and RMS retain their capability to migrate and differentiate in the adult striatum.
Transforming Legal Rights and Social Values: Marriage Redefined

The path to marriage equality in the USA progressed—like previous civil rights moments—over decades, sometimes in waves but at other times with backlash. The movement for marriage equality (the redefinition of the institution of marriage) can be viewed as a rejection of invidious distinctions between the romantic unions of straight couples and gay couples. This story spotlights four moments in legal history culminating with the Obergefell v. Hodges Supreme Court decision on June 26, 2015, legalizing marriage equality nationwide. These legal strategies worked in tandem with state legislation as well as other forms of activism. The analysis shows that courts do not operate in a vacuum. They are both influenced by and influence society and its changing values, with iterative feedback effects.
Converting System Failure Histories Into Future Win Situations

Henry Petroski devotes an entire book to failures in engineering and lessons to be learned [1]. In his preface, he states "the concept of failure mechanical and structural failure in the context of this discussion is central to understanding engineering, for engineering design has as its first and foremost objective the obviation of failure." He further states "the lessons learned from ... disasters can do more to advance engineering knowledge than all the successful machines and structures in the world."
Librarians as Mentors in an Undergraduate Research Program

ABSTRACTProjects in undergraduate research programs differ from assignments in courses in that they are independent of an institution's curriculum, and faculty mentoring plays a more important role. These programs can be fertile ground for librarians interested in participating. Whether such librarians would make good mentors for undergraduate researchers depends largely on their experience and education. Texas Tech University has two of these programs, but library support for them has been sporadic. The time is overdue for librarians involved in campus outreach and instruction to examine how they can best support Texas Tech's undergraduate research activities, and, in particular, whether they are adequately prepared to provide effective mentoring to undergraduate research students. This article reports on such an examination.
Beyond mRNA: The role of non-coding RNAs in normal and aberrant hematopoiesis

The role of non-coding Ribonucleic Acids (ncRNAs) in biology is currently an area of intense focus. Hematopoiesis requires rapidly changing regulatory molecules to guide appropriate differentiation and ncRNA are well suited for this. It is not surprising that virtually all aspects of hematopoiesis have roles for ncRNAs assigned to them and doubtlessly much more await characterization. Stem cell maintenance, lymphoid, myeloid and erythroid differentiation are all regulated by various ncRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and various transposable elements within the genome. As our understanding of the many and complex ncRNA roles continues to grow, new discoveries are challenging the existing classification schemes. In this review we briefly overview the broad categories of ncRNAs and discuss a few examples regulating normal and aberrant hematopoiesis.
Failure of a Polyaryletheretherketone-Cobalt-Chromium Composite Femoral Stem Due to Coating Separation and Subsidence: A Case Report.

CASE A 52-year-old man who previously had undergone total hip arthroplasty with use of an Epoch (Zimmer) extensively porous-coated femoral stem presented with hip pain after a high-energy motor-vehicle accident. Radiographs demonstrated delamination at the polyaryletheretherketone-cobalt-chromium (PEEK-CoCr) core interface, which led to loosening. At revision, the implant demonstrated gross evidence of debonding at the PEEK-CoCr interface. CONCLUSION We demonstrate clinical and tribologic evidence of a rare failure mode involving the PEEK-metal interface in a composite femoral stem, which surgeons should be aware of when evaluating patients with this type of implant.
Allergen Cleaning: Best Practices

Managing allergen changeover in food production facilities can be exceptionally challenging, especially when different allergens are handled on the same line or piece of equipment. Allergen cross-contact can occur when allergen-containing and non-allergen-containing foods or ingredients are produced in the same facility or processing line and allergen controls are not properly implemented. Cleaning is an essential tool for preventing allergen cross-contact during storage, production, and transportation of food. Many factors must be considered when developing cleaning procedures for the purpose of controlling allergens. These include the soil type, the composition and type of food-contact surface, how the food was applied to the surface, the concentration of the allergen in the food, the type and age of the equipment, the length of the processing run, and the type of cleaning method. This chapter discusses the factors that affect removal of allergens from food-contact surfaces, the different approaches for removal of allergenic food soils from food-contact surfaces, best practices and procedures for verifying and validating cleaning treatments for allergen removal and the steps associated with developing an allergen cleaning program. More effective approaches are needed for removing allergens from food-contact surfaces, particularly in the low-moisture foods manufacturing environment. Development of statistically based sampling plans for obtaining samples for cleaning validation and verification activities, and rapid, sensitive, and inexpensive analytical methods for detecting multiple allergens in a single assay are also key research needs.
The Effect of Patient Navigation on the Likelihood of Engagement in Clinical Care for HIV-Infected Individuals Leaving Jail.

Objectives. To compare the effectiveness of patient navigation–enhanced case management in supporting engagement in HIV care upon release from jail relative to existing services.Methods. We randomized 270 HIV-infected individuals to receive navigation-enhanced case management for 12 months or standard case management for 90 days following release from jail between 2010 and 2013. Participants were interviewed at 2, 6, and 12 months after release. We abstracted medical data from jail and city health records.Results. Patient navigation–enhanced case management resulted in greater linkage to care within 30 days of release (odds ratio [OR] = 2.15; 95% confidence interval [CI] = 1.23, 3.75) and consistent retention over 12 months (OR = 1.95; 95% CI = 1.11, 3.46). Receipt of treatment for substance use disorders in jail also resulted in early linkage (OR = 4.06; 95% CI = 1.93, 8.53) and retention (OR = 2.52; 95% CI = 1.21, 5.23). Latinos were less likely to be linked to (OR = 0.35; 95% CI = 0.14, 0.91) or retain...
Use of Security Officers on Inpatient Psychiatry Units.

Objective:Violent and aggressive behaviors are common among psychiatric inpatients. Hospital security officers are sometimes used to address such behaviors. Research on the role of security in inpa...
The Pseudomonas aeruginosa complement of lactate dehydrogenases enables use of D- and L-lactate and metabolic crossfeeding

Pseudomonas aeruginosa is the most common cause of chronic, biofilm-based lung infections in patients with cystic fibrosis (CF). Sputum from patients with CF has been shown to contain oxic and hypoxic subzones as well as millimolar concentrations of lactate. Here, we describe the physiological roles and expression patterns of P. aeruginosa lactate dehydrogenases in the contexts of different growth regimes. P. aeruginosa produces four enzymes annotated as lactate dehydrogenases, three of which are known to contribute to anaerobic or aerobic metabolism in liquid cultures. These three are LdhA, which reduces pyruvate to D-lactate during anaerobic survival, and LldE and LldD, which oxidize D-lactate and L-lactate, respectively, during aerobic growth. We demonstrate that the fourth enzyme, LldA, performs redundant L-lactate oxidation during growth in aerobic cultures in both a defined MOPS-based medium and synthetic CF sputum medium. However, LldA differs from LldD in that its expression is induced specifically by the L- enantiomer of lactate. We also show that all four enzymes perform functions in colony biofilms that are similar to their functions in liquid cultures. Finally, we provide evidence that the enzymes LdhA and LldE have the potential to support metabolic cross-feeding in biofilms, where LdhA can catalyze the production of D-lactate in the anaerobic zone that is then used as a substrate in the aerobic zone. Together, these observations further our understanding of the metabolic pathways that can contribute to P. aeruginosa growth and survival during CF lung infection.
Central Pattern Generators: Sensory Feedback

Sensory feedback plays an essential role in rhythmic animal movements. Although all identified systems that generate such movements include a central oscillator circuit (the central pattern generator, or CPG), sensory receptors provide important, sometimes essential, input that shapes the period, phase, and amplitude of the expressed movement patterns. This article provides an overview of the mechanisms and roles for sensory feedback in the flying, swimming, and walking behaviors of locust, leech, lamprey, stick insect, and crayfish and presents evidence in support of the idea that sensory feedback loops, like the CPGs themselves, are fundamental elements of the oscillator circuits that generate these rhythmic movements.
Purpose of Drugs

Pharmacology is the basic science of drugs; therapeutics is the practical science of how these drugs are used in the treatment of disease. These are fundamental subjects in the art of healing. Many students approach them with fear and trepidation, thinking them exceedingly difficult to understand. While these subjects can be made to appear complex and bewildering, these are also practical subjects, which for our purposes need not be made more strange or difficult than many everyday matters.
Application of High Fidelity Numerical Simulations for Vehicle Aerodynamics

Interest in the use of the large eddy simulation (LES) technique for computation of turbulent flows of industrial relevance has increased considerably. This is in part due to the availability of low cost, powerful supercomputers. Today, a computer cluster capable of one TFOPS sustained performance for a complex flow LES calculation costs about one hundred thousand dollars. Another reason for the increased interest in LES is the recent added capabilities for multi-physics and integrated flow simulations. As part of Stanford’s DOE/ASC program, we have demonstrated and validated high fidelity simulations of multi-phase reacting turbulent flows in highly complex configurations in propulsion systems. The overarching problem in this program is simulation of flow through a complete jet engine, which is an extremely complex machine. LES computations of the entire engine flow are not feasible even with the most advanced supercomputers available. The Reynolds averaged Navier-Stokes (RANS) technique was used for the turbomachinery components and the combustor was simulated using LES. These simulations provided an early example of integrated simulations where different codes with different fidelity compute different portions of the system. A simulation environment had to be developed for the various codes to communicate with each other in an efficient and stable fashion. This integration technology and the associated science are suggested as the means for using LES in vehicle aerodynamics where Reynolds numbers are too high for high fidelity computation of the flow around the entire vehicle. LES can then be used in regions where RANS models are known to be inaccurate, and where LES provides access to flow quantities such as turbulent pressure fluctuations for predicting noise. Several examples of integrated simulations will be presented, including separation control for a high-lift system using synthetic jets.
Genomic analysis of DNA repair genes and androgen signaling in prostate cancer

The cellular effects of androgen are transduced through the androgen receptor, which controls the expression of genes that regulate biosynthetic processes, cell growth, and metabolism. Androgen signaling also impacts DNA damage signaling through mechanisms involving gene expression and transcription-associated DNA damaging events. Defining the contributions of androgen signaling to DNA repair is important for understanding androgen receptor function, and it also has translational implications. We generated RNA-seq data from multiple prostate cancer lines and used bioinformatic analyses to characterize androgen-regulated gene expression. We compared the results from cell lines with gene expression data from prostate cancer xenografts, and patient samples, to query how androgen signaling and prostate cancer progression influences the expression of DNA repair genes. We performed whole genome sequencing to help characterize the status of the DNA repair machinery in widely used prostate cancer lines. Finally, we tested a DNA repair enzyme inhibitor for effects on androgen-dependent transcription. Our data indicates that androgen signaling regulates a subset of DNA repair genes that are largely specific to the respective model system and disease state. We identified deleterious mutations in the DNA repair genes RAD50 and CHEK2. We found that inhibition of the DNA repair enzyme MRE11 with the small molecule mirin inhibits androgen-dependent transcription and growth of prostate cancer cells. Our data supports the view that crosstalk between androgen signaling and DNA repair occurs at multiple levels, and that DNA repair enzymes in addition to PARPs, could be actionable targets in prostate cancer.
Delafloxacin for the Treatment of Acute Bacterial Skin and Skin Structure Infections.

Objective: To review the microbiological activity, safety, and efficacy of the new fluoroquinolone delafloxacin for the treatment of acute bacterial skin and skin structure infections (ABSSSIs). Da...
Ezh2-dCas9 and KRAB-dCas9 enable engineering of epigenetic memory in a context-dependent manner

Rewriting of the epigenome has risen as a promising alternative to gene editing for precision medicine. In nature, epigenetic silencing can result in complete attenuation of target gene expression over multiple mitotic divisions. However, persistent repression has been difficult to achieve in a predictable manner using targeted systems. Here, we report that persistent epigenetic memory required both a DNA methyltransferase (DNMT3A-dCas9) and a histone methyltransferase (Ezh2-dCas9 or KRAB-dCas9). We demonstrate that the histone methyltransferase requirement can be locus specific. Co-targeting Ezh2-dCas9, but not KRAB-dCas9, with DNMT3A-dCas9 and DNMT3L induced long-term HER2 repression over at least 50 days (approximately 57 cell divisions) and triggered an epigenetic switch to a heterochromatic environment. An increase in H3K27 trimethylation and DNA methylation was stably maintained and accompanied by a sustained loss of H3K27 acetylation. Interestingly, substitution of Ezh2-dCas9 with KRAB-dCas9 enabled long-term repression at some target genes (e.g., SNURF) but not at HER2, at which H3K9me3 and DNA methylation were transiently acquired and subsequently lost. Off-target DNA hypermethylation occurred at many individual CpG sites but rarely at multiple CpGs in a single promoter, consistent with no detectable effect on transcription at the off-target loci tested. Conversely, robust hypermethylation was observed at HER2. We further demonstrated that Ezh2-dCas9 required full-length DNMT3L for maximal activity and that co-targeting DNMT3L was sufficient for persistent repression by Ezh2-dCas9 or KRAB-dCas9. These data demonstrate that targeting different combinations of histone and DNA methyltransferases is required to achieve maximal repression at different loci. Fine-tuning of targeting tools is a necessity to engineer epigenetic memory at any given locus in any given cell type.
The Effects of Insulin and Retinoic Acid on the Content of Glucose Transporter 4 in Different Preparation Lysates of L6 Muscle Cells (P15-013-19)

Glucose enters the skeletal muscle cells through glucose transporters (GLUTs), a process that is stimulated by insulin through the movement of GLUT4 to the cell membrane. Here, we studied the effects of retinoic acid (RA) and insulin on GLUT4 expression in L6 muscle cells. Rat L6 muscle cells were induced to differentiation after confluency. Cells were incubated in medium containing 2% HS containing in the absence or presence of 1 μM RA without or with 10 nM insulin for 4 or 6 days with replacement of fresh media every two days. Cells were lyzed and prepared in the following ways. 1) Cells were lyzed in lysis buffer (50 mM HEPES pH 7.5, 10 mM EDTA, 10% Glycerol, 2% NP-40 and 2% Triton X-100) on ice for 20 minutes, vortex cells every 10 minutes to help lyse completely. After that, the lysate was centrifuged at 12,000 x g for 15 minutes at 4°C for the collection of both the supernatant and pellet. 2) Cells were directly lyzed in 1 x SDS loading buffer (designated as total cell lysate here). The GLUT4 protein levels in those samples were determined via Western Blot using anti-GLUT4 antibody (#07-1404, C-terminus) from EMD Millipore Corp. On day 4 or 6, the supernatants of cells treated with RA + insulin had a significantly less GLUT4 expression that that of the control group. Additional, on day 4, the supernatant of cells treated with insulin alone also had less GLUT4 protein than that of the control group. The pellets of cells on day 4 treated with RA had a significantly less GLUT4 protein level than that of the control group. On day 4 or 6, the GLUT4 protein levels in total cell lysates were not significantly different among the four treatment groups. The current lysis buffer allowed us to observe that the treatments of RA and/or insulin can significantly affect GLUT4 protein levels in the supernatants. Given the fact that a significant amount of GLUT4 protein remained in the pellets, the lysis buffer used here could not completely solubilize differentiated L6 cells, suggesting that cautions lysis buffers and methods were chosen carefully to prepare L6 cells for the analysis of GLUT4 protein. Additionally, it also indicates that the differentially solubilized fractions probably provide us tools to study the effects of RA and insulin on the subcellular movement of GLUT4 in L6 muscle cells. The University of Tennessee, Knoxville.
Phosphodiesterase 10A IgG: A novel biomarker of paraneoplastic neurologic autoimmunity.

Objective To describe a novel antibody biomarker of neurologic paraneoplastic autoimmunity specific for phosphodiesterase 10A (PDE10A), a striatum-enriched phosphodiesterase, and to characterize the clinical phenotype of patients with PDE10A immunoglobulin G (IgG). Methods We describe 7 patients with autoantibodies specific for PDE10A identified in the Mayo Clinic Neuroimmunology Laboratory. Patient specimens (sera, 7; CSF, 4) produced identical basal ganglia‐predominant synaptic staining of murine brain tissue by indirect immunofluorescence. The autoantigen was identified by immunoprecipitation and mass spectrometry as PDE10A, and confirmed by antigen-specific recombinant Western blot and cell-based assays, and immune absorption experiments. Results The median patient age was 70 years (range 66–76); 4 were men. Four patients with clinical information available had movement disorders (hyperkinetic in 3 [chorea, ballismus, dystonia] and parkinsonism in 1). All patients but one had cancer (lung [adenocarcinoma 1, squamous cell carcinoma 1, poorly differentiated mesenchymal carcinoma 1], renal adenocarcinoma 2, and pancreatic adenocarcinoma 1). Two of the 7 patients developed hyperkinetic movement disorders during treatment with immune checkpoint inhibitors (nivolumab and pembrolizumab), though none of 26 cancer control patients treated with immune checkpoint inhibitors harbored PDE10A IgG in their serum. MRIs from those 2 patients with hyperkinetic movement disorders demonstrated fluid-attenuated inversion recovery/T2 basal ganglia hyperintensities, and their CSF harbored unique oligoclonal bands. One of those 2 patients had substantial improvement after corticosteroids. One patient9s renal adenocarcinoma expressed PDE10A by immunohistochemistry. Conclusions PDE10A IgG defines a novel rare neurologic autoimmune syndrome and expands the spectrum of diagnosable paraneoplastic CNS disorders. The intracellular location of PDE10A suggests a T-cell-mediated pathology targeting cells displaying MHC1-bound PDE10A peptides.