cssi/SciSciGPT-SciSciNet huggingface dataset:
Enhanced trauma program commitment at a level I trauma center: effect on the process and outcome of care

Hypothesis With advances in surgical care, the occurrences of major adverse outcomes have become a rare event. the effect of a surgical service can be more comprehensively evaluated by following the donabedian model, looking at the triad of structure, process, and outcome. it is hypothesized that the implementation of a focused program commitment at a trauma center is associated with improvements in process of care and patient outcomes. Design Evaluation of prospectively collected information in a trauma registry for the 3-year periods immediately before (1995-1997) and after (1999-2001) the implementation (in 1998) of the full-time trauma service. Setting Level i university-affiliated trauma center. Patients Patients meeting criteria for major trauma. Intervention The implementation of a full-time trauma service, featuring 24-hour in-house attending coverage, dedicated trauma admitting unit, regular trauma core curriculum, regular multidisciplinary quality assurance meetings, and state designation for level i status. Main outcome measures Process of care measures, including time in the emergency department (ed) and trauma "bypass" hours (ie, time spent in the trauma resuscitation area). outcome measures, including lengths of stay, overall mortality and mortality, excluding ed deaths. Results The total number of patients with major trauma increased from 2240 (1995-1997) to 2513 (1999-2001). the average time in the ed for patients going to the operating room, intensive care unit, and observation wards all decreased significantly (84 vs 52 minutes, 197 vs 118 minutes, and 300 vs 140 minutes, respectively; all with P P P = .07) and mortality rates among patients with severe head injury (23.8% vs 17.2%, P = .07). on further analyses with multiple logistic regression, controlling for age, injury severity score, abbreviated injury score (for a head injury), and admission blood pressure, the later period is associated with a 31% decrease in overall odds of death ( P = .047) and a 42% decrease in odds of death among patients with severe head injury (an abbreviated injury score, ≥3; P = .03). Conclusion The implementation of a full-time trauma service is associated with improved timeliness of triage and therapeutic interventions and improved patient outcomes.
Group II introns: highly specific endonucleases with modular structures and diverse catalytic functions

Group II introns are large catalytic RNAs with a remarkable repertoire of reactions. Here we present construct designs and protocols that were used to develop a set of kinetic frameworks for studying the structure and reaction mechanisms of group II introns and ribozymes derived from them. In addition, we discuss application of these systems to structure/function analysis of the ai5γ group II intron.
First Indications of Geological Activity on Triton

In his News of the Week article “Neptune's icy cold satellite comes to life” (15 Oct., p. [383][1]), Richard A. Kerr reports on new work that has led to a “startling” realization that Triton “is still showing signs of [geological] life,” and he mentions observations hinting that Triton's “geological activity has made itself evident in recent years.” The article also has quotes from scientists talking about “real surprises” and that the implication of the new work is that Triton “probably still is active.” However, the article does not mention the discovery from the Voyager 2 mission 10 years ago of active smoking vents on Triton, which led the Voyager team to conclude (Reports, 15 Dec. 1989, p. 1417) that sparsely cratered Triton has “a geologically young surface…and at least two geyser-plumes.” What appears to be new in the work Kerr reports about is not the youthful surface or the geologic activity, but interesting constraints on the resurfacing parameters, global spectral changes, and impactor environment of Triton. # Response {#article-title-2} As Hartmann notes, the Voyager team concluded that Triton has “a geologically young surface,” but, at the time, geologically young meant that the average age of the surface was perhaps 1 billion years, and even the youngest surfaces could have been half a billion years old (p. 1448 and Table 5 in Reports, 15 Dec. 1989, p. 1422). The recent drop in perceived average surface age to 100 million years and perhaps much lower has let some planetary scientists conclude that geological activity driven by internal heat (not solar-driven geysers) is resurfacing Triton. [1]: /lookup/doi/10.1126/science.286.5439.383
Cognitive, anxiety and mood disorders in the fragile X-associated tremor/ataxia syndrome

Objective: We evaluated patients with fragile X-associated tremor/ataxia syndrome (FXTAS), a neurodegenerative disorder associated with a CGG repeat expansion in the premutation range in the fragile X mental retardation 1 (FMR1) gene. Methods: Neurological, psychiatric and neuropsychological evaluations were performed on 15 male patients with FXTAS. Results: Seven cases were diagnosed with dementia, and seven others were diagnosed with mood and/or anxiety disorders. Twelve subjects demonstrated deficits on neuropsychological testing. Conclusions: Physicians assessing dementia patients are urged to consider this newly described syndrome, especially in patients with dementia associated with a movement disorder and in those with a family history of mental retardation. If FXTAS is a possible diagnosis, physicians may carry out FMR1 DNA testing; patients who test positive on DNA testing should undergo magnetic resonance imaging, be referred to neurology and receive genetic counseling.
Effect of media composition on the induction of chorionic gonadotropin by sodium butyrate in HeLa cells.

Production of the glycoprotein hormone α-subunit by HeLa cells and its induction by sodium butyrate are dependent on the choice of culture medium. Under identical growth conditions it was found that subunit synthesis in the presence of butyrate was highest in RPMI 1640, lowest in Medium 199 (M199), and intermediate in minimum essential medium (MEM) and Waymouth's MB 752/1. Cell growth was similar in all media examined and was retarded in the presence of butyrate. Alkaline phosphatase activity was also lower in M199 than in RPMI 1640, although, in general, the magnitude of this difference was less than that for the hormone subunit. Incorporation of [1-14C]butyrate by HeLa cells was simimar in both M199 and RPMI 1640, indicating that uptake and metabolism of the fatty acid were not significantly different under these conditions. In the presence of 3 mM butyrate, mixtures of RPMI 1640 and M199 gave intermediate levels of α-subunit and alkaline phosphatase compared to each medium alone. Intracellular levels of α-subunit as well as that of the culture medium were reduced in M199 compared to RPMI 1640 indicating that synthesis rather than secretion was altered.
Multiple hormone response elements can confer glucocorticoid regulation on the human insulin receptor gene.

Glucocorticoids have been shown to increase the levels of cell surface insulin receptors and their mRNA in many different cell types. Previously, we have reported that glucocorticoids induce the transcription of the human insulin receptor (hIR) gene in rat 208F cells and we also identified a putative glucocorticoid response element (GRE) to which the glucocorticoid receptor binds in a specific manner. In this study we have mapped four additional regions of the hIR promoter to which glucocorticoid receptor binds specifically; one residues at -1340 and the others are distributed within a 100 base pair region from -750 to -650. Within each DNase I footprinting region resides at least one putative GRE sequence. They function as GREs to confer glucocorticoid inducibility when fused to a heterologous promoter-chloramphenicol acetyltransferase reporter construct. The functional significance of these putative GREs was further substantiated by mutational analysis. Taken together, our results indicate that these GR...
Aberrant coronary arteries: a reliable echocardiographic screening method

Abstract Background Aberrant origin (ABO) of a coronary artery (CA) from the contralateral aortic sinus with a subsequent interarterial course is a life-threatening condition. It carries a 28% to 55% risk for a sudden coronary event or death, but there are no reliable screening methods. Objective We sought to determine whether imaging a cross section of a coronary segment in the anterior aortic wall on the long-axis view may be used as an echocardiographic screening sign for ABO CA. Methods The echocardiograms of all patients with ABO CA were evaluated for the screening sign and compared with those of age-matched control patients. Results Between January 1989 and October 2002, we identified 8 patients with ABO CA (median age: 15 years). Of these patients, 4 were symptomatic and 4 were discovered incidentally. The electrocardiogram produced normal findings in 5 of 8 patients, maximal stress test produced normal findings in 5 of 6 patients, and thallium perfusion test produced negative results in 2 of 3 patients. There were 4 patients with ABO in the main left CA, 3 with ABO in the right CA, and 1 with ABO in the circumflex CA branch. The screening sign was readily visible in 7 of the 8 patients (88%), and all 7 of these patients had ABO in a main CA. Only in the ABO in the circumflex CA branch was the screening sign not detected. The 1743 control patients (median age: 14 years) showed normal anterior aortic wall, which was void of any CA segment. In 5 control patients (0.3%, P Conclusion We concluded that the proposed screening sign for ABO CA is reliable and easily recognizable, and should prompt a comprehensive assessment of the CA.
A Reassessment of Clarity in Written Managerial Communications

Current thinking about effective written communication does not systematically assess the complex role that language plays in organizations. This article calls for a contingency view of communication clarity and effectiveness based on the impact that an organization's language customs have on perceived effectiveness. To justify this need for a contingency approach, we examine the psychological-social function of organizational language and discuss the role that language has in creating new knowledge in organizations.
Research and treatment approaches to depression

Depression is a major cause of disability worldwide, but we know little about the underlying fundamental biology. Research is hindered by the difficulties of modelling a disorder of higher cognitive functions in animals. Depression can be understood as the interaction of genetic susceptibility and environmental factors; however, current classifications are purely descriptive. The complexity of this field is best approached by rigorous explorations of known candidate systems in conjunction with the use of genomic tools to discover new targets for antidepressants and to predict therapeutic outcomes.
RNA-directed remodeling of the HIV-1 protein Rev orchestrates assembly of the Rev–Rev response element complex

The HIV-1 protein Rev controls a critical step in viral replication by mediating the nuclear export of unspliced and singly-spliced viral mRNAs. Multiple Rev subunits assemble on the Rev Response Element (RRE), a structured region present in these RNAs, and direct their export through the Crm1 pathway. Rev-RRE assembly occurs via several Rev oligomerization and RNA-binding steps, but how these steps are coordinated to form an export–competent complex is unclear. Here, we report the first crystal structure of a Rev dimer-RRE complex, revealing a dramatic rearrangement of the Rev-dimer upon RRE binding through re-packing of its hydrophobic protein–protein interface. Rev-RNA recognition relies on sequence-specific contacts at the well-characterized IIB site and local RNA architecture at the second site. The structure supports a model in which the RRE utilizes the inherent plasticity of Rev subunit interfaces to guide the formation of a functional complex. DOI: http://dx.doi.org/10.7554/eLife.04120.001
Role of angiotensin II in bladder smooth muscle growth and function.

Outlet obstruction of the developing urinary bladder may result in pathologic changes in the bladder wall that can adversely affect lower urinary tract dynamics and worsen compliance. When obstruction is not recognized and persists, upper tract deterioration and renal function compromise may ensue. This process occurs in several pediatric urologic conditions such as posterior urethral valves or urethral atresia. Bladder neck obstruction may also be neurogenic in origin as is the case in many children with myelomeningocele (spina bifida). The exact cellular mechanisms and pathways that regulate obstructive changes in the developing bladder have yet to be elucidated. Viewing this process simplistically, physiologic impairment of urinary flow likely causes increased bladder wall stress from retained urine and over distension of bladder muscle. This increased mechanical stress then causes a cascade of cellular events which results in secondary changes in bladder wall architecture. The most prominent histopathologic findings in the obstructed bladder are muscular hypertrophy/hyperplasia and increased extracellular matrix protein deposition.1–3 Resultant changes in muscle and collagen content, alterations in cellular architecture, and changes in bladder compliance have adverse effects on the bladder’s ability to function as a low pressure reservoir for urinary storage. Also, bladder wall compliance changes may in turn produce further problems with increased wall stress that can then lead to a viscous cycle of events which can result in a small non functional bladder in need of surgical reconstruction.
Use of FWD Data for Pavement Material Characterization and Performance

Conventionally used FWD backcalculation and pavement stress-strain computation procedures are based on linear static layered elastic theory. This paper presents a simple hypothetical case study in which the applicability of the assumptions made in the foregoing procedures is investigated using the finite-element method. The pavement displacements computed using static/dynamic falling-weight deflectometer (FWD) loading and constant and stress-dependent material properties were used as input for the backcalculation analysis. The assumed and backcalculated layer moduli were compared. The backcalculated asphalt concrete (AC) moduli values were within acceptable limits for all pavement sections studied except for the case of the thin AC pavement with a shallow rigid base. The subgrade moduli were consistently underpredicted; the base course moduli were both underpredicted and overpredicted. Widely used traffic-induced pavement strains that are related to pavement performance that were obtained under different loading and material property characterizations were also compared. Results indicate that the conventional procedures are not conservative, especially for thick AC pavement sections.
A novel mechanism for telomere size control in Saccharomyces cerevisiae.

One of the central requirements for eukaryotic chromosome stability is the maintenance of the simple sequence tracts at telomeres. In this study, we use genetic and physical assays to reveal the nature of a novel mechanism by which telomere length is controlled. This mechanism, telomeric rapid deletion (TRD), is capable of reducing elongated telomeres to wild-type tract length in an apparently single-division process. The deletion of telomeres to wild-type lengths is stimulated by the hprl mutation, suggesting that TRD in these cells is the consequence of an intrachromatid pathway. Paradoxically, TRD is also dependent on the lengths of the majority of nonhomologous telomeres in the cell. Defects in the chromatin-organizing protein Sir3p increase the rate of Aprl-induced rapid deletion and specifically change the spectrum of rapid deletion events. We propose a model in which interactions among telosomes of nonhomologous chromosomes form higher order complexes that restrict the access of the intrachromatid recombination machinery to telomeres. This mechanism of size control is distinct from that mediated through telomerase and is likely to maintain telomere length within a narrow distribution.
Curriculum deceleration and on-line learning communities for working students

Online interactive learning communities and a decelerated five-year engineering program, are proposed as possible strategies for increasing the number of undergraduate students obtaining degrees in science, technology, engineering, and mathematics fields. These strategies are aimed at minimizing the differences in the learning environment and the support systems at residential campuses and those at urban commuter schools. The learning communities provide on-line mentoring and tutorial support to all the community members. Initial focus is to establish on-line interactive learning communities for all incoming students led by the student engineering professional societies. Five-year decelerated curricula for both electrical engineering and computer engineering programs have been developed, which are currently being used to advise students. Preliminary results from the on-line learning communities for incoming students are very encouraging.
The Two Voices of Alzheimer's: Attitudes Toward Brain Health by Diagnosed Individuals and Support Persons

Purpose: Most individuals with Alzheimer's are cared for in their homes by unpaid family members. Research on caregiving focuses disproportionally on costs of care, service utilization, and negative psychosocial outcomes. Few narrative accounts of Alzheimer's exist; those that do suffer similar pejorative framings and narrow foci. No studies that we are aware of examine the health beliefs of diagnosed individuals and support persons, or their attitudes about brain health. This research reports perceptions of ?aging well? held by those most intimately acquainted with Alzheimer's. Design and Methods: Diagnosed individuals and their support persons (N = 85) were enrolled into 14 focus groups. Grounded theory methods were used to collect, code, and analyze textual interview data into overarching themes. Results: Respondents found physical and mental health, social activity, independence, and happiness integral to aging well. An acceptance of various limitations was also deemed crucial. Support persons placed more emphasis on lifestyle factors and memory loss as potential obstacles. Diagnosed respondents defined memory loss in less medicalized terms, whereas support persons labeled it Alzheimer's and negatively characterized those affected. Both groups warned against discussing ?prevention? of dementia: Diagnosed individuals noted the implication of ?aging poorly? and support persons cautioned against blaming diagnosed individuals. Implications: These findings can be used to encourage positive health beliefs and behaviors tailored to the needs of diagnosed seniors and their families, to help practitioners and researchers identify and become sensitive to differences between and among older adults, and to further advance the utility of narrative accounts for informing health interventions and education efforts.
The Methodology of Normative Policy Analysis.

Policy analyses frequently clash. Their disagreements stem from many sources, including models, empirical estimates, and values such as who should have standing and how different criteria should be weighted. We provide a simple taxonomy of disagreement, identifying distinct categories within both the positive and values domains of normative policy analysis. Using disagreements in climate policy to illustrate, we demonstrate how illuminating the structure of disagreement helps to clarify the way forward. We conclude by suggesting a structure for policy analysis that can facilitate assessment, comparison, and debate by laying bare the most likely sources of disagreement.
Influence of dietary intake and lasalocid on serum hormones and metabolites and visceral organ growth and morphology in wether lambs

Twenty-four black face, crossbred wether lambs (32.4 6.1 kg) were assigned to one of four treatments arranged in a 2 2 factorial. Individually penned wethers were fed a pelleted total mixed diet at low intake (LI; 60% of ad libitum) or high intake (HI; 95% of ad libitum); diets contained either low lasalocid (LL; 0 mg per lamb daily) or high lasalocid (HL; 40 mg per lamb daily). Measurements of serum hormones and metabolites were taken during two 3-day collection periods following a 14-day adjustment to treatments. After 42‐45 day on treatments, wethers were slaughtered and weight (wt) of liver and intestinal segments were recorded and tissues subsampled. Serum insulin and glucose concentrations were increased (p 0.10) by intake or lasalocid. Lasalocid had little influence on metabolic hormones or growth and development of visceral organs. These data indicate that high intake increased serum insulin and glucose concentrations, liver wt and cell size. # 2000 Elsevier Science B.V. All rights reserved.
Pain as a Joint Function of Alcohol Intake and Customary Reasons for Drinking

Nonalcoholics who, on a problem drinking inventory, responded “yes” to items reflecting a psychological dependence on alcohol, tended after alcohol ingestion to report a decrease in pain experienced in a cold pressor test. Conversely, those whose responses indicated no psychological dependence on alcohol tended to report pain increases after the consumption of alcohol.
Relative status regulates risky decision making about resources in men: evidence for the co-evolution of motivation and cognition

Relative social status strongly regulates human behavior, yet this factor has been largely ignored in research on risky decision making. Humans, like other animals, incur risks as they compete to defend or improve their standing in a social group. Among men, access to culturally important resources is a locus of intrasexual competition and a determinant of status. Thus, relative status should affect men's motivations for risk in relevant domains. Contrasting predictions about such effects were derived from dominance theory and risk-sensitive foraging theory. Experiments varied whether subjects thought they were being observed and evaluated by others of lower, equal or higher status, and whether decisions involved resources (status relevant) or medical treatments (status irrelevant). Across two experiments, men who thought others of equal status were viewing and evaluating their decisions were more likely to favor a high-risk/high-gain means of recouping a monetary loss over a no-risk/low-gain means with equal expected value. Supporting predictions from dominance theory, this motivation for risk taking appeared only in the equal status condition, only for men, and only for resource loss problems. Taken together, the results support the idea that motivational systems designed to negotiate a status-saturated social world regulate the cognitive processes that generate risky decision making in men.
Oxidation‐Based Model for Thermal Barrier Coating Life

A procedure is described for modeling the lives of thermal barrier coatings subjected to high-temperatrue environments. The models is used to calculate cycles-to-failure as a function of heating cycle duration. It is based on the presumption that oxidation is the single important time-dependent factor which limits the life of these coatings, and that oxidation-induced strains combine with cyclic strains to promote slow crack growth in the ceramic layer. Good agreement is obtained between calculated and experimental lives for specimens tested in a furnace. This shows that an oxidation-based approach is promising. The importance of reproducible specimen preparation is also discussed.
pH-induced hysteretic gating of track-etched polycarbonate membranes: swelling/deswelling behavior of polyelectrolyte multilayers in confined geometry.

pH-induced hysteretic gating of track-etched polycarbonate membranes (TEPC) has been achieved by depositing layer-by-layer assembled polyelectrolyte multilayers comprising poly(allylamine hydrochloride) (PAH) and poly(sodium 4-styrenesulfonate) (PSS) at a high pH condition (pH > 9.0). Scanning electron microscopy and transmission electron microscopy showed that the average bilayer thickness of multilayers was greater within the cylindrical pores of track-etched polycarbonate membranes compared to the multilayers on planar substrates (e.g., Si wafers and the face of TEPC membranes). Swelling/deswelling properties of multilayers and gating properties of the multilayer-modified TEPC membranes were studied by measuring the flux of pH-adjusted deionized water. Large discontinuous changes in the transmembrane flux were observed, indicating that the multilayers within the cylindrical pores of TEPC membranes exhibit the discontinuous swelling/deswelling behavior observed previously for planar systems. The degree ...
OFDM MIMO radar for low-grazing angle tracking

We develop a low-grazing angle (LGA) tracking method considering realistic physical and statistical effects, such as earth's curvature, vertical refractivity gradient of standard lower atmosphere, and non-Gaussian characteristics of sea-clutter. We employ a co-located multiple-input-multiple-output (MIMO) radar configuration using wideband orthogonal frequency division multiplexing (OFDM) signalling scheme. Apart from the frequency diversity provided by OFDM, we also exploit polarization to resolve the multipath signals by using polarization-sensitive transceivers. Thus, we can track the scattering coefficients of the target at different frequencies along with its position and velocity. We apply a sequential Monte Carlo method (particle filter) to track the target. Our numerical examples demonstrate the achieved performance improvements due to realistic physical modeling and OFDM MIMO configuration.
Combination of Methylphenidate, Venlafaxine, and Escitalopram Resulting in Serotonin Syndrome

Objective:To report a case of possible serotonin syndrome resulting from the addition of methylphenidate and/or escitalopram to venlafaxine.Case Summary:A 23-year-old woman being treated for bipola...
One-Month Test–Retest Reliability of the ImPACT Test Battery

In order to better understand the test–retest reliability of the ImPACT test battery, 25 undergraduate students completed two ImPACT tests across a time frame of 4 weeks between assessments. Participants had not previously completed ImPACT and had no history of concussion. Pearson’s correlation coefficients (r) and intraclass correlation coefficients (ICCs) were as follows: Verbal Memory ¼ .66/.79 (r/ICC), Visual Memory ¼ .43/.60, Visual Motor Speed ¼ .78/.88, Reaction Time ¼ .63/.77, and Total Symptoms ¼ .75/.81. Dependent sample ttests revealed significant improvement on only Visual Motor Speed composite scores. Reliable Change Indices showed a significant number of participants fell outside 80% and 95% confidence intervals for only Visual Motor Speed scores (but no other indices), whereas all scores were within 80% and 95% confidence intervals using regression-based measures. Results suggest that repeated exposure to the ImPACT test may result in significant improvements in the physical mechanics of how college students interact with the test (e.g., performance on Visual Motor Speed), but repeated exposure across 1 month does not result in practice effects in memory performance or reaction time.
Programming advanced control functions for enhanced intelligence of industrial robots

Industrial robots are important elements in automated production systems. Programming industrial robots requires the knowledge of robot motion controls. In this paper, some of the advanced control functions of industrial robots are discussed with the examples of FANUC robot program instructions. This includes applying the functions of robot payload estimation, robot stiffness control, and robot collision detection for enhanced robot intelligence.
HES-Mediated Repression of Pten in Caenorhabditis elegans

The hairy/enhancer-of-split (HES) group of transcription factors controls embryonic development, often by acting downstream of the Notch signaling pathway; however, little is known about postembryonic roles of these proteins. In Caenorhabditis elegans, the six proteins that make up the REF-1 family are considered to be HES orthologs that act in both Notch-dependent and Notch-independent pathways to regulate embryonic events. To further our understanding of how the REF-1 family works to coordinate postembryonic cellular events, we performed a functional characterization of the REF-1 family member, HLH-25. We show that, after embryogenesis, hlh-25 expression persists throughout every developmental stage, including dauer, into adulthood. Like animals that carry loss-of-function alleles in genes required for normal cell-cycle progression, the phenotypes of hlh-25 animals include reduced brood size, unfertilized oocytes, and abnormal gonad morphology. Using gene expression microarray, we show that the HLH-25 transcriptional network correlates with the phenotypes of hlh-25 animals and that the C. elegans Pten ortholog, daf-18, is one major hub in the network. Finally, we show that HLH-25 regulates C. elegans lifespan and dauer recovery, which correlates with a role in the transcriptional repression of daf-18 activity. Collectively, these data provide the first genetic evidence that HLH-25 may be a functional ortholog of mammalian HES1, which represses PTEN activity in mice and human cells.
Erratum for Rao et al., treatment outcomes with cefazolin versus oxacillin for deep-seated methicillin-susceptible Staphylococcus aureus bloodstream infections.

Volume 59, no. 9, p. [5232–5238][1], 2015. Page 5235, left column, lines 18–20: “had a shorter median (IQR) time to achieving source control (1.5 [0 to 3] days versus 2 [1 to 4] days” should read “had a longer median (IQR) time to achieving source control (2 [1 to 4] days versus 1.5 [0 to
Individual nephron function in experimental bilateral pyelonephritis. II. Distal tubular sodium and water reabsorption and the concentrating defect.

Abstract The renal concentrating defect in rats with nonobstructive bilateral pyelonephritis was studied by combined clearance and micropuncture methods. Control groups consisted of normal rats and those in which approximately 65 to 70 per cent of renal mass had been ablated by bilateral subtotal nephrectomy. The residual functioning renal mass and solute load per nephron were estimated to be of about the same order of magnitude in the pyelonephritic and partially nephrectomized animals. It was found, however, that both U max and t c h 2 o were diminished to a greater extent in the rats with intrinsic renal disease. Measurements of osmolality, sodium, and inulin concentrations in the distal tubular fluid of surviving cortical nephrons failed to reveal any specific defect in sodium transport by the thick ascending limb of Henle's loop, or any change in the permeability characteristics which could account for the severity of the concentrating defect in the pyelonephritic animals. The data suggest, rather, that at comparable rates of total solute excretion in the urine, individual surviving loops of Henle in the pyelonephritic rats were actually transporting more sodium into the medullary interstitium than were the loops in the normal controls. The concentrating defect in the pyelonephritic animals thus could not be accounted for by the reduction in renal mass, by the adaptational increases in glomerular filtration rate per surviving nephron, or by any detectable defect in salt or water transfer in individual cortical nephrons. The observations localize the disturbance to the renal medulla. It is suggested that disruption of the architecture of the renal medulla may be an important factor contributing to the concentrating defect.
Transforming mental health services to address gender disparities in depression risk factors

Depression in older women is a significant and growing problem. Women who experience life stressors across the life span are at higher risk for developing depression than their male counterparts. Research has focused primarily on identifying and reducing the symptoms of depression for the general aging population, disregarding gender-specific differences in the foundational causes of depression. This article examines how women’s unique experiences influence the development of depression and highlights how the current mental health system could better meet older women’s needs by moving from a gender-neutral model to one that emphasizes women’s experiences.
Phase II Trial of CI-958 in Recurrent Platinum-Refractory Ovarian Carcinoma: A Gynecologic Oncology Group Study

Abstract Objectives. The objectives of this study were twofold: (1) to estimate the anti-tumor efficacy of CI-958 in patients with measurable platinum-resistant ovarian cancer; (2) to determine the nature and degree of toxicity of CI-958 in these patients. Methods. Patients received CI-958 560 mg/m 2 intravenously every 3 weeks and tumor measurements were performed every one to two cycles. Results. In 25 cases with recurrent platinum-resistant disease, there was one partial response (PR) and six patients had stable disease (SD). Conclusions. CI-958 has minimal activity in platinum-resistant ovarian cancer at the dose and schedule tested.
Co2+ binding to alpha-lactalbumin.

α-Lactalbumin possesses multiple Zn2+ binding sites, with the strongest site having an affinity constant of 5×105 M−1 [Permyakovet al. (1991),J. Protein Chem. 100, 577]. The binding of zinc at secondary sites is accompanied by destabilization of the protein structure and progressive protein aggregation. This pronounced destabilization is reflected in a shift of the thermal denaturation transition temperature by more than 40°. The present work examines Co2+ binding to bovineα-lactalbumin, where for this analog of Zn2+, multiple binding sites were also found from spectrofluorimetric titrations. The strong site Co2+ binding constant was 1.3×106 M−1. However, in contrast to Zn2+ binding, Co2+ does not cause protein aggregation nor any significant thermal destabilization of the protein. Fluroescence energy transfer measurements between Tb3+ in the strong calcium site to Co2+ in the strong Zn2+ site gave a distance in the range of 14–18 A, which was in excellent agreement with recent crystallographic data for humanα-lactalbumin [Renet al. (1993), J. Biol. Chem.268, 19292–19298] However, the X-ray structure did not identify the additional zinc sites found from earlier solution studies, presumably due to restrictive crystal packing interactions. The results from the current work confirm that the strong cobalt (zinc) site in solution is the same zinc site elucidated by X-ray crystallography.
The Bad and the Evil: Justice in the Novels of Pago Ignacio Taibo II

This chapter discusses how the work of Taibo is capable of extremely creative approaches to the forms of criminality specific to neoliberal globalization, despite the fact that his work contains many features that are quite traditional. Taibo’s main protagonist, Hector Belascoaran Shayne, is, in many ways, a prototypical private eye; his novels are usually set entirely in Mexico City, and his villains are usually individuals who may, or may not, be held accountable for their actions. Nevertheless, as Schmid explains, Taibo consistently identifies the (Mexican) state as a criminal actor and his individual criminals are always complexly overdetermined synecdoches of state criminality who either work in concert with members of the police, army, and government, or are actual members of those organizations. The crimes investigated in Taibo’s novels frequently extend far beyond the confines of both Mexico City and Mexico itself in that the criminal activities Taibo focuses on are often transnational in scope, such as drug smuggling, gun running, and the subversion of democratic governments in other countries. Despite the traditional nature of his setting, protagonist, and antagonists, Taibo is ultimately concerned with what he regards as the most serious form of contemporary crime: global neoliberalism.
Methylphenidate-Induced Seizure, ADHD and Abnormal EEG

Investigators from Harvard Medical School, Boston, present the case of a 6-year-old girl with ADHD taking valproic acid for behavioral problems who had a generalized tonic-clonic convulsion shortly after a first dose of methylphenidate.
Impact of Therapeutics On Fatigue in Chronic Immune Thrombocytopenia (ITP).

Abstract Abstract 4455 Complaints of tiredness, lethargy or lack of energy are common in patients with chronic Immune ThrombocytoPenia (ITP), however they are not well understood. This study assessed whether different clinical and laboratory aspects are related to fatigue and how different therapeutic modalities might impact these symptoms. Methods Patients with chronic ITP older than 15 years old were enrolled from 2007-2008 at the Platelet Disorders Center at the Weill-Cornell Medical Center, NY. They completed the Short-Form 36 questionnaire (SF-36) and Fatigue severity scale (FSS) (2 standardized Health-related quality of life [HRQoL] questionnaires) and the Beck Depression Inventory (BDI). Laboratory testing included CBC, TSH, ferritin, iron + TIBC, and blood serotonin levels. Results 83 patients with a mean age of 40.2 years (67.5% women) were enrolled. The mean platelet counts were 109,000/ul (range of 12,000-500,000/ul). Forty-one % of patients had duration of ITP of 10 years or more and 25% had had previous splenectomy. Sixty-one% were on treatment: 11% steroids, 23% Tpo-R agents and 28% “Other” (7.2 % Rigel, 13.3 % IVIG, 3.6 % anti-D, 2.4 % rituximab and 1.2% Danazol/Azathioprine). Surprisingly, analysis of the SF36 showed that the study (ITP) population is similar to the general US population and that they do not report increased fatigue or depression. These results contrast with a previous report by McMillan, AJH, 2007 (fig 1). However when the current patients were divided according to age, abnormal low scores on SF36 were observed on vitality domain (mean 50) for the age group of 45-55 years and on role physical domain (mean 48) for the age group of 55-65 years. Furthermore, differences were observed in patients stratified according to treatment (figure 2) where the mean scores for patients on the steroid group on the respective domains were lower: vitality 49 and role physical 42. The Tpo-R agonists group had better results in all SF36 domains; similar findings were seen with the FSS and BDI. The only laboratory finding is that patients with low ferritin levels had worse results on FSS. Conclusion Although fatigue and related symptoms have been previously reported by others including an improvement with successful treatment eg in studies of the TPO-R agonists, to our surprise we did not find the same results. Whether this study population is intrinsically different or receiving different treatments, eg avoidance of steroids, might impact these results here are 2 possible hypotheses. Use of different fatigue assessments as ITP-PAQ or CDC symptom inventory and further studies addressing the role of the pro-inflammatory cytokines in these patients would be useful. Disclosures: No relevant conflicts of interest to declare.
The new cult of Pax Augusta 13 BC – AD 14

As Augustus returned to Rome in 13 BC, the Senate passed a constitutio to build in his honor a lasting altar of peace, the Ara Pacis Augustae, to signal with a major ceremony the new peace all over the Roman world, Gibbon’s Pax Romana. As we know from Ovid Fast. 1. 709–714, 3. 881–882, the Ara Pacis was the site of two annual sacrifices (on 30 Jan. and 30 March) to Pax, an innovation of the Augustan Age, for formerly Pax had been a minor goddess without a temple. The Augustan regime elevated a new form of Pax as a religious cult and made it acceptable to the Roman people, who had regarded Pax as the phenomenon of a foreign power too beaten down to resist Roman arms any longer and had no use for pacifism (in the modern sense), which would be seen only as cowardly in their dangerous world. Augustus had started this process, perhaps not intentionally, back when he closed the Gates of Janus in 29. By bringing together Greco-Roman elements of Pax with Jupiter and Janus, he was able to forge a new religious cul...
The Effect of a Histone Deacetylase Inhibitor (AR-42) on Canine Prostate Cancer Growth and Metastasis.

Background Canine prostate cancer (PCa) is an excellent preclinical model for human PCa. AR-42 is a histone deacetylase inhibitor (HDACi) developed at The Ohio State University that inhibits the proliferation of several cancers, including multiple myeloma, lung, and hepatocellular cancer. In this study, we investigated whether AR-42 would prevent or decrease. The growth and metastasis of a canine PCa (Ace-1 cells) to bone in vitro and in vivo. Methods Proliferation, cell viability, invasion, and metastasis of a canine prostate cancer cell line (Ace-1) were measured following treatment with AR-42. Expression of anoikis resistance, epithelial-to-mesenchymal transition (EMT), and stem cell-related markers were also evaluated. To assess the efficacy of AR-42 on prevention of PCa metastasis to bone, Ace-1 cells were injected in the left cardiac ventricle of nude mice, mice were treated with AR-42, and the incidence and growth of bone metastasis were measured. Bioluminescence was performed to monitor the bone metastases in nude mice. Results AR-42 inhibited the in vitro proliferation of Ace-1 cells in a time- and dose-dependent manner. The IC50 concentration of AR-42 for Ace-1 cells was 0.42 μM after 24 hr of treatment. AR-42 induced apoptosis, decreased cell migration, and increased the stem cell properties of Ace-1 cells in vitro. AR-42 downregulated E-cadherin, N-cadherin, TWIST, MYOF, anoikis resistance, and osteomimicry genes, while it upregulated SNAIL, PTEN, FAK, and ZEB1 gene expression in Ace-1 cells. Importantly, AR-42 decreased the bioluminescence and incidence of bone metastasis in nude mice. In addition, AR-42 induced apoptosis and altered the tumor cell morphology to an irregular cell phenotype with condensed chromatin in the bone metastases. Conclusion AR-42 decreased PCa growth and bone metastasis, induced apoptosis, and downregulated osteomimicry genes in PCa cells in the bone microenvironment. Prostate 77:776-793, 2017. © 2017 Wiley Periodicals, Inc.
Synthetic Lethality Screens Using RNAi in Combination with CRISPR-based Knockout in Drosophila Cells

A synthetic lethal interaction is a type of genetic interaction where the disruption of either of two genes individually has little effect but their combined disruption is lethal. Knowledge of synthetic lethal interactions can allow for elucidation of network structure and identification of candidate drug targets for human diseases such as cancer. In Drosophila, combinatorial gene disruption has been achieved previously by combining multiple RNAi reagents. Here we describe a protocol for high-throughput combinatorial gene disruption by combining CRISPR and RNAi. This approach previously resulted in the identification of highly reproducible and conserved synthetic lethal interactions (Housden et al., 2015).
Non-autonomous Cellular Responses to Ototoxic Drug-Induced Stress and Death.

The first major recognition of drug-induced hearing loss can be traced back more than seven decades to the development of streptomycin as an antimicrobial agent. Since then at least 130 therapeutic drugs have been recognized as having ototoxic side- effects. Two important classes of ototoxic drugs are the aminoglycoside antibiotics and the antineoplastic agent cisplatin. These drugs save the lives of millions of people worldwide, but they also cause irreparable hearing loss. In the inner ear, sensory hair cells (HCs) and spiral ganglion neurons (SGNs) are important cellular targets of these drugs, and most mechanistic studies have focused on the cell-autonomous responses of these cell types in response to ototoxic stress. Despite several decades of studies on ototoxicity, important unanswered questions remain, including the cellular and molecular mechanisms that determine whether HCs and SGNs will live or die when confronted with ototoxic challenge. Emerging evidence indicates that other cell types in the inner ear can act as mediators of survival or death of sensory cells and spiral ganglion neurons. For example, glia-like supporting cells (SCs) can promote survival of both HCs and SGNs. Alternatively, SCs can act to promote HC death and inhibit neural fiber expansion. Similarly, tissue resident macrophages activate either pro-survival or pro-death signaling that can influence HC survival after exposure to ototoxic agents. Together these data indicate that autonomous responses that occur within a stressed HC or SGN are not the only (and possibly not the primary) determinants of whether the stressed cell ultimately lives or dies. Instead non-autonomous cellular responses are emerging as significant determinants of HC and SGN survival vs. death in the face of ototoxic stress. The goal of this review is to summarize the current evidence on non-autonomous cellular responses to ototoxic stress and to discuss ways in which this knowledge may advance the development of therapies to reduce hearing loss caused by these drugs.
The relationship between family-based adverse childhood experiences and substance use behaviors among a diverse sample of college students

Abstract Introduction Research suggests that college students are an especially vulnerable subset of the population for substance use and misuse. However, despite evidence of the high prevalence of adverse childhood experiences (ACE) among students and the link between family-based ACE and substance use among older adults, this relationship remains understudied in college populations. Moreover, whether ACE represents a shared risk across substance use behaviors and ethnic groups is unknown. Methods Data are student responses ( n = 2953) on the 2015 American College Health Association's National College Health Assessment II (ACHA-NCHA II) administered at one of the largest, most diverse public universities in California. Multivariable logistic and negative binomial regression models tested the association between individual and accumulated ACE and past 30-day alcohol, tobacco, marijuana, and illicit drug use, past 12-month prescription medication misuse and polysubstance use. Results Between 50% and 75% of students involved in substance use were ACE exposed. There was a significant dose-response relationship between ACE and substance use and polysubstance use. Although accumulated ACE increased risk for substance use, there was considerable ethnic variability in these associations. Conclusions The graded effects of ACE for substance use underscore the link between family-based stressors and these behaviors in emergent adult college students. Our findings make a compelling case for investing in health initiatives that prioritize ACE screening and access to trauma-informed care in campus communities. Continued research with college populations is needed to replicate findings and clarify the role of ethnicity and culture in trauma response and help seeking behaviors.