cssi/SciSciGPT-SciSciNet huggingface dataset:
Drug abuse's smallest victims: in utero drug exposure.

Abstract The social and economic impact of drug use on our global population continues to increase leaving no geographical, social or cultural group untouched. The National Institute on Drug Abuse (NIDA), in one of the few large surveys of maternal abuse, found that 5.5% of mothers reported taking an illicit substance during gestation. These figures certainly are underestimates due to the stigma of drug use during pregnancy and the accompanying legal, ethical and economic issues. Although drugs of choice and routes of administration vary by country, exposure of our most valuable resource, our children, to the developmental effects of drugs is an enormous problem. In utero drug exposure can have a severe impact not only on the development of the fetus, but also on the child during later stages of life. More than 75% of infants exposed to drugs have major medical problems as compared to 27% of unexposed infants. The cost of treating drug-affected infants was twice the cost of non-affected infants. Obstetrical complications including placental insufficiency, miscarriage, intrauterine death, and increased incidence of infectious and sexually-transmitted diseases are higher in the drug-abusing mother. Treatment for pregnant addicts should be a high priority for our governments. Increased awareness and improvement in our understanding of drug abuse in the medical, legal and social realms will enable us to reduce the barriers to treatment for this important population. Accurate identification of in utero drug exposure has important implications for the care of the mother and child, but can raise difficult legal issues. Society discourages prenatal care with the infliction of harsh criminal penalties. Maternal drug use during pregnancy can be monitored with urine, sweat, oral fluid and/or hair testing. Detection of in utero drug exposure has traditionally been accomplished through urine testing; however, the window of detection is short, reflecting drug use for only a few days before delivery. Monitoring exposure through testing of alternative matrices, such as neonatal meconium and hair, offers advantages including non-invasive collection and detection earlier in gestation. There are many unresolved issues in monitoring in utero drug exposure that urgently require research. These can be divided into research to definitively differentiate drug exposed and non-drug-exposed fetuses, determine the most efficient methods to routinely monitor women’s drug use, and determine how these drug test results relate to neonatal and maternal outcomes. Research in this area is difficult and expensive to perform, but necessary to assess accurately drug effects on the fetus. By increasing our understanding of the physiological, biochemical and behavioral effects of gestational drug exposure, we may ultimately provide solutions for better drug prevention, treatment and a reduction in the number of drug-exposed children.
Effects and Causes of Discrepancies in Supply Operations

A matter that has received scant attention in the literature of operations research is the role of discrepancies between physical stocks and stocks of record in a supply operation. Discrepancies not only exert a deleterious effect on the performance of the supply function, but may have a serious effect on the realization of benefits to be derived from implementation of theoretically optimal methods of inventory control and procurement or production scheduling. The present paper reports on a case study of discrepancies and their causes in a supply facility of an agency of the Federal Government. Contrary to the general expectation that the massive and complex paper work system connected with processing of issues and receipts was the principal source of discrepancies, it was possible to determine that about 80 per cent of the discrepancies were caused by the discrepancy-correcting procedures themselves. As a result two principal targets for further study are clearly delineated, 1 the inventorying process and 2 the stock balance adjustment procedures. Even on the basis of preliminary study some ameliorating recommendations were possible.
Diffraction of shock waves by a moving thin wing

An analytical solution is obtained for the flow field due to the impinging of a plane shock wave of arbitrary strength by a thin wing moving in the opposite direction. The planform and the thickness distribution of the wing can be arbitrary and the speed of the wing can be either supersonic or subsonic relative to the undisturbed stream ahead of the shock or to that behind the shock. The solution is a generalization of the previous solution of Ting & Ludloff for the diffraction of shock wave by a two-dimensional stationary airfoil to a three-dimensional wing moving with supersonic or subsonic speed relative to the stream ahead of or behind the shock. The solution is employed for the analysis of the changes in aerodynamic forces when an airplane encounters a blast wave or a shock wave of another airplane. It is also used to study the diffraction of a shock wave or an N-wave advancing over flat terrains.
The Mechanism of Reca Pola Lethality: Suppression by Reca-Independent Recombination Repair Activated by the Lexa(def) Mutation in Escherichia Coli

The mechanism of recA polA lethality in Escherichia coli has been studied. Complementation tests have indicated that both the 59-->39 exonuclease and the polymerization activities of DNA polymerase I are essential for viability in the absence of RecA protein, whereas the viability and DNA replication of DNA polymerase I-defective cells depend on the recombinase activity of RecA. An alkaline sucrose gradient sedimentation analysis has indicated that RecA has only a minor role in Okazaki fragment processing. Double-strand break repair is proposed for the major role of RecA in the absence of DNA polymerase I. The lexA(Def)::Tn5 mutation has previously been shown to suppress the temperature-sensitive growth of recA200(Ts) polA25::spc mutants. The lexA(Def) mutation can alleviate impaired DNA synthesis in the recA200(Ts) polA25::spc mutant cells at the restrictive temperature. recF+ is essential for this suppression pathway. recJ and recQ mutations have minor but significant adverse effects on the suppression. The recA200(Ts) allele in the recA200(Ts) polA25::spc lexA(Def) mutant can be replaced by delta recA, indicating that the lexA(Def)-induced suppression is RecA independent. lexA(Def) reduces the sensitivity of delta recA polA25::spc cells to UV damage by approximately 10(4)-fold. lexA(Def) also restores P1 transduction proficiency to the delta recA polA25::spc mutant to a level that is 7.3% of the recA+ wild type. These results suggest that lexA(Def) activates a RecA-independent, RecF-dependent recombination repair pathway that suppresses the defect in DNA replication in recA polA double mutants.
Toxicology and overdose of atypical antipsychotics.

Abstract Background Second-generation antipsychotic medications, or “atypical antipsychotics,” are now first-line therapy in the treatment of schizophrenia and other psychotic disorders, and are additionally being used in a wide array of other psychiatric and non-psychiatric conditions in both adults and children. Overdose is frequently reported to poison control centers. Objectives We review the toxicology and general management of poisonings involving the atypical antipsychotic medications. Discussion The most serious toxicity involves the cardiovascular system and the central nervous system. All typical and atypical antipsychotics cause sedation, which is pronounced in overdose. The most common cardiovascular effects that occur after atypical antipsychotic overdose are tachycardia, mild hypotension, and prolongation of the QTc interval. Other clinical syndromes in overdose include neuroleptic malignant syndrome (NMS) and antimuscarinic delirium. Seizures may be observed. No antidotes exist for these poisonings, but they most often do well with supportive care. Conclusion Antipsychotic overdose produces a gamut of manifestations that affect multiple organ systems. Treatment is primarily supportive. Specific therapies for NMS, hypotension, and seizures are discussed.
The p53-mdm-2 autoregulatory feedback loop

The p53 protein can bind to a set of specific DNA sequences, and this may activate the transcription of genes adjacent to these DNA elements. The mdm-2 gene is shown here to contain a p53 DNA-binding site and a genetically responsive element such that expression of the mdm-2 gene can be regulated by the level of wild-type p53 protein. The mdm-2 protein, in turn, can complex with p53 and decrease its ability to act as a positive transcription factor at the mdm-2 gene-responsive element. In this way, the mdm-2 gene is autoregulated. The p53 protein regulates the mdm-2 gene at the level of transcription, and the mdm-2 protein regulates the p53 protein at the level of its activity. This creates a feedback loop that regulates both the activity of the p53 protein and the expression of the mdm-2 gene.
Personal Sound Amplifiers for Adults with Hearing Loss

Age-related hearing loss is highly prevalent and often untreated. Use of hearing aids has been associated with improvements in communication and quality of life, but such treatment is unaffordable or inaccessible for many adults. The purpose of this review is to provide a practical guide for physicians who work with older adults who are experiencing hearing and communication difficulties. Specifically, we review direct-to-consumer amplification products that can be used to address hearing loss in adults. Helping adults with hearing loss navigate hearing loss treatment options ranging from being professionally fitted with hearing aids to using direct-to-consumer amplification options is important for primary care clinicians to understand given our increasing understanding of the impact of hearing loss on cognitive, social, and physical functioning.
The Causes of Post-Merger Underperformance: Evidence from Successful and Unsuccessful Bidders

There are at least two plausible explanations for the post-merger underperformance: information asymmetry and performance extrapolation. The first hypothesis maintains that acquirers are over-valued before the mergers, while the second one maintains that acquirers become over-valued as a result of the mergers. Based on a book-to-market analysis, Rau and Vermaelen (1998) conclude that the performance extrapolation hypothesis is more consistent with the data than the information asymmetry hypothesis. The evidence provided in this study leads to the opposite conclusion. Consistent with the information asymmetry hypothesis, I find evidence of long-term underperformance in failed as well as successful bids. More importantly, controlling for potential sample selection biases and other relevant variables, I find no evidence that bidders' long-term abnormal returns are related to the success of the bids. I also find that the book-to-market effect, provided by Rau and Vermaelen (1998) as evidence in support of the performance extrapolation hypothesis, is driven by firms in the banking industry. In general, the results of the study are consistent with the information asymmetry hypothesis and inconsistent with the performance extrapolation hypothesis.
Mutations induced by ionizing radiation in a plasmid replicated in human cells. II. Sequence analysis of α-particle-induced point mutations

The human shuttle plasmid pZ189, containing the Escherichia coli supF gene as the mutational target, was irradiated in vitro with 210Po alpha particles and transfected into human lymphoblastoid cells. Plasmids which were replicated in human cells were recovered and those containing mutant supF genes were isolated by phenotypic screening in E. coli. The mutations were characterized by sequencing the tRNA gene. The mutant frequency increased linearly with the alpha-particle dose and, at 259 Gy, it was 16 times (0.29%) that observed in unirradiated controls (0.018%). The distribution of alpha-particle-induced point mutations was highly nonrandom and similar to that observed in the unirradiated or X-irradiated plasmid DNAs. The majority of the mutations were G.C----A.T transitions and occurred selectively at most 5'-TC (3'-AG) and 5'-CC (3'-GG) sequences. For the unirradiated control DNA, these mutations at C's (G's) were preferentially located in the nontranscribed strand, similar to the observation previously made for mutations in X-irradiated DNA. Such a strand bias was not observed for mutations in the alpha-particle-irradiated DNA. The data suggest that, although similar types of point mutations are induced in unirradiated, X-irradiated, and alpha-particle-irradiated DNAs, the mechanisms of their induction and the exact nature of the lesions involved may be quite different.
Hydrodeoxygenation of 4-Propylguaiacol (2-Methoxy-4-propylphenol) in a Microreactor: Performance and Kinetic Studies

Catalytic hydrodeoxygenation of 4-propylguaiacol, a model compound for lignin-derived components of pyrolysis oil, was performed in a packed-bed microreactor. The effects of various processing cond...
Electrophoresis of Prolan.

SummaryAlcohol prolan shows the electrokinetic behavior of a single chemical individual. The isoelectric point is more acid than pH 3.5. Brucine prolan behaves as a mixture. The physiological activity of prolan is attributed to a grouping which may survive chemical treatment drastic enough to alter the protein-like carrier.
The mTOR Complexes in Cancer Cell Metabolism

Cells metabolize nutrients to generate energy and building materials for growth and proliferation. In highly proliferating cells, such as cancer cells, there is an increased demand for nutrients with concomitant rerouting of metabolic pathways in favor of biosynthetic processes. This rewiring is accomplished by cross talk between growth signaling and metabolic pathways. At the hub of these pathways is the mechanistic or mammalian target of rapamycin (mTOR), a protein kinase that senses nutrients and growth signals. mTOR forms two protein complexes, termed mTOR complex 1 (mTORC1) and mTORC2, by partnering with distinct proteins. Several studies strongly support a central role for mTORC1 in metabolic reprogramming but there is also emerging evidence for mTORC2 involvement in this process. This review focuses on the role of both complexes in different metabolic and biosynthetic processes in which they have been linked so far, with special emphasis on the role of mTORCs in cancer metabolic reprogramming. We also discuss the clinical relevance of targeting mTOR and metabolic pathways for cancer therapy.
Romantische Geschichtsphilosophie: Die Christenheit oder Europa

Zu Friedrich von Hardenbergs unausgefuhrten schriftstellerischen Planen gehorte »Die Errichtung eines litterairischen, republicanischen Ordens — der durchaus mercantilisch politisch ist — einer achten Cosmopolitan Loge«, wie er in einem Brief an Friedrich Schlegel vom 10. Dezember 1798 schreibt (IV, 268f). Caroline Schlegel, die die Starken und Schwachen der Fruhromantiker recht gut kannte, neckte Hardenberg in ihrem Brief vom 4. Februar 1799, er habe sie recht bose gemacht »mit Ihren Dithyramben uber das mercantilische Genie, das uns fehlt und Sie auch nicht haben« (IV, 518). Darin hatte sie wohl recht, aber es gab zumindest einige Grunde dafur, warum Hardenberg zu dieser Zeit auf einen solchen Plan kam. Am Anfang Dezember 1798 hatten die Bruder Schlegel nach langen Verhandlungen erfahren, dass ihre Zeitschrift Das Athenaeum bei einem neuen Verleger, Heinrich Frohlich, doch fortgesetzt werden konnte. Insofern leuchtet es ein, dass der erste geplante Schritt in der Etablierung eines literarischen Ordens eine »Buchdruckerey — ein Buchhandel« war: »Ihr sollt nicht mehr von Buchhandlern litterairisch und politisch gewissermaasen dependiren« (IV, 269). Die Erwahnung von Jena, Hamburg oder der »Schweitz, wenn Frieden wird«, als moglicher »Sitz des Bureaus« (ebd.) deutet an, dass Hardenberg u.a. auch an die Umgehung von Zensurbestimmungen dachte.
Impact of the Cancer Prevention and Control Research Network: Accelerating the Translation of Research Into Practice

The Cancer Prevention and Control Research Network (CPCRN) is a thematic network dedicated to accelerating the adoption of evidence-based cancer prevention and control practices in communities by advancing dissemination and implementation science. Funded by the Centers for Disease Control and Prevention and National Cancer Institute, CPCRN has operated at two levels: Each participating network center conducts research projects with primarily local partners as well as multicenter collaborative research projects with state and national partners. Through multicenter collaboration, thematic networks leverage the expertise, resources, and partnerships of participating centers to conduct research projects collectively that might not be feasible individually. Although multicenter collaboration is often advocated, it is challenging to promote and assess. Using bibliometric network analysis and other graphical methods, this paper describes CPCRN's multicenter publication progression from 2004 to 2014. Searching PubMed, Scopus, and Web of Science in 2014 identified 249 peer-reviewed CPCRN publications involving two or more centers out of 6,534 total. The research and public health impact of these multicenter collaborative projects initiated by CPCRN during that 10-year period were then examined. CPCRN established numerous workgroups around topics such as: 2-1-1, training and technical assistance, colorectal cancer control, federally qualified health centers, cancer survivorship, and human papillomavirus. This paper discusses the challenges that arise in promoting multicenter collaboration and the strategies that CPCRN uses to address those challenges. The lessons learned should broadly interest those seeking to promote multisite collaboration to address public health problems, such as cancer prevention and control.
Review: Drug treatment of hypertension reduces mortality in the elderly

Source Citation Insua JT, Sacks HS, Lau TS, et al. Drug treatment of hypertension in the elderly: a meta-analysis. Ann Intern Med. 1994 Sep 1;121:355-62.
Effect of gross morphology on modern planktonic foraminiferal test strength under compression

Planktonic foraminifera are a source of important geochemical, palaeoceanographic, and palaeontological data. However, many aspects of their ecology remain poorly understood, including whether or not gross morphology has an ecological function. Here, we measure the force needed to crush multiple planktonic foraminiferal morphotypes from modern core top and tow samples. We find significant differences in the resistance of different morphotypes to compressional force. Three species, Globorotalia tumida (biconvex, keeled), Menardella menardii (discoidal, keeled), Truncorotalia truncatulinoides (conical, keeled), require on average 59% more force (1.07 v. 0.47 N) to crush than the least resistant species ( Orbulina universa and Trilobatus sacculifer ) in core-top samples. Towed samples of pre-gametogenic individuals also show significant differences of the same magnitude (0.693 v. 0.53 N) between the conical ( T. truncatulinoides ) and globular/spherical morphologies ( Globoconella inflata and O. universa ). We hypothesize that the greater compressional strength of certain shapes confers a fitness advantage against predators and could contribute to the repeated, convergent evolution of keeled, conical and bi-convex forms in planktonic foraminifer lineages. Supplementary material: Raw data for all crushing experiments, wall thickness measurements, and results for all pair-wise Kolmogorov-Smirnov Tests are available at https://doi.org/10.6084/m9.figshare.c.3725236.v1
The Whole Price of Vancomycin: Toxicities, Troughs, and Time.

Vancomycin is a glycopeptide antibiotic that is active against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. Nephrotoxicity, which is usually reversible, is the most serious common adverse effect of vancomycin. Vancomycin-associated nephrotoxicity prolongs hospital stays, imposes a need for additional antibiotics and, in rare circumstances, dialysis treatment, and increases medical costs and mortality. Risk factors for nephrotoxicity include the dose and duration of vancomycin treatment, serum trough concentration, patient characteristics, and concomitant receipt of nephrotoxins. Contemporary guidelines recommend targeting vancomycin trough concentrations of ≥10 mg/L to prevent resistance and trough concentrations of 15–20 mg/L to optimize outcomes. There is significant correlation between vancomycin trough serum concentrations and the incidence of vancomycin-associated nephrotoxicity; however, evidence of an association between trough concentrations and efficacy is less convincing. Routine monitoring of serum vancomycin concentrations consumes time and limited healthcare resources and may not be cost effective. The use of alternative antibacterial agents that do not require monitoring would free up pharmacy resources. This time could then be devoted to initiatives such as pharmacist-led antibiotic stewardship programs that are known to reduce antibiotic use and promote improved patient outcomes.
Applications of Superconductivity to Fundamental Research in Physics

Attempts to utilize the complete absence of electrical resistance and other characteristic properties of superconductors for technological purposes started almost immediately after the discovery of the phenomenon itself. For nearly fifty years, however, applications were confined to specialized devices in which superconducting components were employed mainly for research in low temperature Physics. In the early sixties, the discovery of high field super-conductorsl, tunneling2 and the Josephson effects3 suddenly changed the picture, and in the short period of just over a decade, the subject of applied superconductivity has grown to such an extent, that it is now virtually impossible for an individual even to enumerate all the applications, let alone discuss them in any detail. For this reason, I shall confine myself to brief descriptions of a few selected applications which are currently employed in low temperature and high energy physics. The choice is somewhat arbitrary, being dictated by my own interests and by the fact that recent applications of superconductivity are having a large impact on experimental particle physics. Some of the applications discussed are relatively simple, both in concept and in technical details, and can be made to function by using inexpensive equipment. For the benefit of non specialists, the physics of these applications is discussed in simple terms and the technical details are avoided. They can be found in the list of references given at the end.
Pressure drop analysis of direct liquid cooled (DLC) rack

This study presents an experimental and numerical characterization of pressure drop in a commercially available direct liquid cooled (DLC) rack. It is important to investigate the pressure drop in the DLC system as it determines the required pumping power for the DLC system, which affects the energy efficiency of the data center. The main objective of this research is to assess the flow rate and pressure distributions in a DLC system to enhance the reliability and the cooling system efficiency. Other objectives of this research are to evaluate the accuracy of flow network modeling (FNM) in predicting the flow distribution in a DLC rack and identify manufacturing limitations in a commercial system that could impact the cooling system reliability. The main components of the investigated DLC system are: coolant distribution module (CDM), supply/return manifold module, and server module which contains a cold plate. Extensive experimental measurements were performed to study the flow distribution and to determine the pressure characteristic curves for the server modules and the coolant distribution module (CDM). Also, a methodology was described to develop an experimentally validated flow network model (FNM) of the DLC system to obtain high accuracy. The measurements revealed a flow maldistribution among the server modules, which is attributed to the manufacturing process of the micro-channel cold plate. The average errors in predicting the flow rate of the server module and the CDM using FNM are 2.5% and 3.8%, respectively. The accuracy and the short run time make FNM a good tool for design, analysis, and optimization for DLC systems. The pressure drop in the server module is found to account for 56% of the total pressure drop in the DLC rack. Further analysis showed that 69% of the pressure drop in the server module is associated with the module's plumbing (corrugated hoses, disconnects, fittings). The server cooling modules are designed to provide secured connections and flexibility, which come with a high pressure drop cost.
Satisfaction guaranteed? Life satisfaction, institutional factors, and self-employment

Abstract There has been a recent growing interest in the relationship between self-employment and life satisfaction. Using an institutional theory lens, in a multilevel model we test the association between shared prosperity and business freedom on life satisfaction reported by self-employed. Specifically, with increasing shared prosperity, self-employed individuals report higher life satisfaction. Furthermore, in countries with higher shared prosperity and greater business freedom, self-employed report a higher life satisfaction. We discuss the implications of our findings and provide future research directions into the link between life satisfaction, institutional factors, and self-employment.
Abstract ES8-2: Exosome analysis in breast cancer: Clinical translation

There is a growing appreciation that tumor secreted factors can function by orchestrating the cross-talk between cancer, stromal and immune cells. Tumors constitutively release membrane-derived extracellular vesicles (EVs) or exosomes that are readily detected in body fluids and have been appreciated to play important roles in signaling, immunomodulation and metastasis. We examined the role of circulating and stromal-derived EVs in hormonal therapy resistant breast cancer. We identified the full mitochondrial genome in circulating extracellular vesicles (EVs) from patients with hormonal-therapy resistant metastatic breast cancer. We generated xenograft models of hormonal therapy-resistant (HTR) metastatic disease characterized by EVs in the peripheral circulation containing mtDNA. Moreover, these human HT-resistant cells had acquired host-derived (murine) mtDNA promoting ER-independent metabolic proficiency. Functional studies identified cancer associated fibroblasts (CAF)-derived EVs (from patients and xenograft models) laden with the complete mitochondrial genome as a mediator of this phenotype. Specifically, the treatment of HT-naive cells or HT-treated metabolically dormant populations with CAF-derived mtDNAhi EVs promoted an escape from metabolic quiescence and HTR disease both in vitro and in vivo. Moreover, this phenotype was associated with the acquisition of EV-mtDNA especially in cancer stem-like cells, expression of EV-mtRNA and restoration of metabolic activity. In addition to mtDNA, we also identified miR-221 in CAF derived EVs as a driver of HTR disease. Specifically, EV-mediated transfer of miR-221 to cancer cells and, in combination with hormone therapy, activated an ERlo/Notchhi feed-forward loop responsible for the generation of CD133hi cancer stem like cells. We further determined that the IL6-pStat3 pathway promoted the biogenesis of onco-miR-221hi CAF EVs. Our results illuminate how EV-mediated horizontal transfer of genetic material from host stromal cells to cancer cells triggers the evolution of therapy-resistant metastases, with potentially broad implications for their control. Citation Format: Bromberg JF. Exosome analysis in breast cancer: Clinical translation [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr ES8-2.
Globalization, Collective Action, and Social Theory

Like economics, the social sciences have long focused on processes and institutions within single states and societies. Until very recently, "global" or "transnational" were concepts that were either alien or marginal to mainstream social-science theories. "International" and "world" were of course understood, but supranational developments could hardly be fathomed. Outside of the mainstream, dependency theory and its more sophisticated variant, world-systems theory, challenged Marxism's emphasis on class conflicts within single societies, drawing attention to the transnational nature of capital and labor flows and the implications thereof for economic and political processes at the societal level, as well as for the reproduction of global inequalities. Back in the mainstream, theories of social movements and political protest also focused on national-level dynamics-and mainly in the West. But no sooner had these theories gained prominence in the 1980's than new developments began to challenge some of their basic assumptions. These new developments included forms of governance and forms of activism at the global level. Globalization compels a rethinking
High-speed quiet tunnels

The powerful adverse effect of wind tunnel noise on boundary layer transition was conclusively demonstrated about two decades ago by the remarkable correlations of Pate and Schueler at AEDC. They showed that transition Reynolds numbers were accurately correlated by noise dependent parameters in several different tunnels over the Mach number range from 3 to 20. Their correlations established that the high levels of wind tunnel noise were caused by acoustic noise radiation from the tunnel walls. Later at the Langley Research Center, Stainback showed that a quantitative relationship exists between wind tunnel rms pressure levels and transition.
Weekly irinotecan and concurrent radiation therapy for stage III unresectable NSCLC.

Median survival in patients with advanced urothelial carcinoma continues to be approximately 1 year following treatment with traditional cisplatin (Platinol)-based regimens, which have substantial toxicity. Thus, research is focusing on newer chemotherapeutic agents and novel combination regimens to improve outcomes and tolerability. Paclitaxel (Taxol) demonstrated one of the highest single-agent response rates (42%) in patients with advanced urothelial tumors, prompting extensive evaluation of combination regimens, including paclitaxel/platinum-based doublets or triplets. In many trials, carboplatin (Paraplatin) has been substituted for cisplatin to produce a more convenient, less toxic regimen. These trials have demonstrated that paclitaxel/platinum-based combinations are similar in efficacy to traditional cisplatin-based regimens and are generally better tolerated. Consequently, paclitaxel-based combinations (e.g., paclitaxel/carboplatin) are now considered alternative treatment options for patients with advanced disease, particularly those who are ineligible for clinical trials or are unable to tolerate standard cisplatin-based regimens. Paclitaxel/ifosfamide (Ifex)/cisplatin is another promising alternative regimen for patients who can tolerate cisplatin-based regimens. An ongoing phase III trial comparing paclitaxel/carboplatin and MVAC (methotrexate, vinblastine, Adriamycin, and cisplatin) should clarify the role of paclitaxel-based combinations. Paclitaxel-based combinations are also under evaluation in the adjuvant setting, and future trials may assess their potential role as neoadjuvant therapy or in combination with radiation therapy.
GALACTIC MORPHOLOGY AND SCALE.

An exact theory of the geometric equilibrium of physical isopleths has been obtained under satisfaction of the isoplethic condition, (24.1), the trace condition, (25.3), and the assumption that the isopleth may be viewed as a timelike hypersurface S that carries a jump discontinuity in the momentum-energy tensor. The culmination of these considerations was the discretization equation, (25.6), for the determination of the scalar function Ψ that gives the modulus of the vector field that generates the irrotational isometry of S that is required by the conditions of geometric equilibrium. If the results of the previous Chapter are examined, it is seen that a significant portion of the resulting structure of a physical isopleth in a state of geometric equilibrium is determined by precisely the function Ψ. The properties of the function Ψ, as determined by the solutions of the discretization equations are obtained in this Chapter. Before this is done, however, we implement conditions that relate the general theory of equilibrium isopleths to galactic structures. This is done, in effect, by the requirement that a galactic isoplethic surface admit time-slices that are homotopic to the surface of an oblate spheroid in three-dimensional Euclidean space.
Functional method for some nonlinear problems in plasma physics and thermonuclear fusion

A Volterra-Wiener functional scheme for solving nonlinear equations is presented. Several problems in plasma physics and thermonuclear fusion which can be solved accurately by using this method are discussed. A nonlinear kinetic-theory problem of plasma shocks is solved as an example.
Bacterial Arthritis of the Hip Due to Lemierre Syndrome: A Case Report.

Case A 20-year-old woman presented to the emergency department with a painful left hip. Clinical evaluation and investigation led to the diagnosis of bacterial arthritis of the left hip. After undergoing an irrigation and debridement, the patient became hypoxic and critically ill from sepsis due to Lemierre syndrome. Conclusion Lemierre syndrome is a rare clinical scenario that may present with bacterial arthritis secondary to septic embolization. Patients have anaerobic bacteremia and diffuse septic embolization that may spread to a joint and the lungs. This syndrome has substantial morbidity and mortality.
‘Shrieking soldiers … wiping clean the earth’: hearing apocalyptic environmentalism in the music of Botanist

This article presents a case study of ecocritical black metal, delving into the apocalypticism of the California-based black metal band Botanist, who conjures a world in which plants have violently destroyed human civilisation. It first contextualises Botanist amidst the broader current of environmentalism in extreme metal as well as within wider cultural explorations of plants as subjective beings capable of violence. The article then examines how Botanist taps into the logic of apocalyptic environmentalism, as the music presents the essential narrative of apocalyptic bioterrorism: humanity, with wanton hubris, has sown the seeds of its own destruction, and earned whatever horrors befall it on the way to elimination. With its bleak outlook and strident sound world, Botanist's music threatens to destabilise listeners’ assumptions about their place in the world and offers an example of what apocalyptic ecological urgency in music could sound like.
Ionic exchange and fibre contraction.

IN a communication under the above title, published in Nature of May 31, 1947, p. 746, J. L. Mongar and A. Wassermann report some experiments on the de-swelling of calcium alginate fibres in salt solutions. They noted that water-swollen alginate fibres when placed in various alkali-salt solutions first contract and then increase in length. The authors suggest that the contraction results from destruction of calcium ion cross-links between alginate chains as the calcium is replaced by alkali ions. They propose also that plastic flow is mainly responsible for the final swelling effect.
Where the Fault Lies: Representations of Addiction in Audience Reactions to Media Coverage of the Opioid Epidemic:

The unprecedented number of deaths in the U.S. attributed to opioids has been referred to as an “epidemic of addiction.” Media coverage of the epidemic has stoked public discussion of addiction on ...
Transverse Single-Spin Asymmetries of Midrapidity Direct Photons, Neutral Pions, and Eta Mesons in 200 GeV Polarized Proton-Proton Collisions at PHENIX

Experimental observations of strikingly large transverse single-spin asymmetries (TSSAs) opened a window into quark and gluon dynamics present in hadronic collisions, revealing large spin-momentum correlations within nucleons and in the process of forming hadrons. Though originally measured in lower energy fixed target experiments, they have been found to persist in collisions with momentum transfer well into the perturbative regime of quantum chromodynamics (QCD) and yet their origin remains poorly understood. TSSA measurements have allowed for the development of both transverse momentum dependent and collinear twist-3 descriptions of nonperturbative spin-momentum correlations for both initial- and final-state effects. Results are presented for the TSSAs of direct photons, neutral pions, and eta mesons in the pseudorapidity range $|\eta|<0.35$ from $p^\uparrow+p$ collisions with $\sqrt{s} = 200$ GeV at PHENIX. As hadrons, $\pi^0$ and $\eta$ mesons are sensitive to both initial- and final-state effects. At midrapidity, $\pi^0$ and $\eta$ measurements are sensitive to the dynamics of gluons along with a mix of quark flavors. These results are a factor of three increase in statistical precision and extend to higher transverse momentum when compared with previous PHENIX measurements in this kinematic region. Because direct photon production does not include hadronization, the direct photon TSSA is only sensitive to spin-momentum correlations in the proton. The kinematics of this result in particular make the direct photon TSSA a clean probe of gluon dynamics in the transversely polarized proton. All three of these asymmetries will help constrain the twist-3 trigluon collinear correlation function as well as the gluon Sivers function, improving our knowledge of spin-dependent gluon dynamics in QCD.
Variations in Hepatitis B Vaccine Series Completion by Setting Among Adults at Risk in West Virginia

Introduction West Virginia leads the nation with the highest rate of acute hepatitis B. From 2013 to 2015, the West Virginia hepatitis B Vaccination Pilot Project distributed more than 10,000 doses of hepatitis B vaccine to at-risk adults through local health department clinics and through outreach to correctional facilities and substance use treatment centers. This study aims to determine which setting type is associated with the greatest likelihood of at-risk adults receiving all 3 or at least 2 doses of hepatitis B vaccine. Methods Data for this retrospective cohort study were accessed, extracted, and analyzed in 2019 from Pilot Project participant forms initially completed from 2013 to 2015. Odds of receiving all 3 or at least 2 doses were calculated using bivariate, multivariable, and mixed-effects regression models. Results Data were available for 1,201 participants. In multivariable logistic regression, participants vaccinated at substance use treatment centers (AOR=1.37, 95% CI=1.01, 1.86) and local health department family planning clinics (AOR=3.74, 95% CI=1.98, 7.06) were more likely to receive the 3-dose series versus those vaccinated at local health department sexually transmitted disease clinics. Participants vaccinated through substance use treatment centers (AOR=1.79, 95% CI=1.31, 2.44), correctional facilities (AOR=3.34, 95% CI=2.09, 5.34), and local health department family planning clinics (AOR=3.97, 95% CI=1.72, 9.16) were more likely to receive at least 2 doses. Conclusions Hepatitis B vaccination delivered at local health department family planning clinics, substance use treatment centers, or correctional facilities may increase vaccine dose completion in West Virginia.
FDA Approval Summary: Selpercatinib for the Treatment of Lung and Thyroid cancers with RET Gene Mutations or Fusions

On May 8, 2020, the FDA granted accelerated approval to selpercatinib for (i) adult patients with metastatic RET fusion-positive non-small cell lung cancer (NSCLC), (ii) adult and pediatric patients ≥12 years of age with advanced or metastatic RET-mutant medullary thyroid cancer who require systemic therapy, and (iii) adult and pediatric patients ≥12 years of age with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine refractory (if radioactive iodine is appropriate). Approval was granted on the basis of the clinically important effects on the overall response rate (ORR) with prolonged duration of responses observed in a multicenter, open-label, multicohort clinical trial (LIBRETTO-001, NCT03157128) in patients whose tumors had RET alterations. ORRs within the approved patient populations ranged from 64% [95% confidence interval (CI), 54-73] in prior platinum-treated RET fusion-positive NSCLC to 100% (95% CI, 63-100) in systemic therapy-naive RET fusion-positive thyroid cancer, with the majority of responders across indications demonstrating responses of at least 6 months. The product label includes warnings and precautions for hepatotoxicity, hypertension, QT interval prolongation, hemorrhagic events, hypersensitivity, risk of impaired wound healing, and embryo-fetal toxicity. This is the first approval of a drug specifically for patients with RET alterations globally.
Utilizing time-driven activity-based costing to determine open radical cystectomy and ileal conduit surgical episode cost drivers

Abstract Objectives Patients undergoing radical cystectomy represent a particularly resource-intensive patient population. Time-driven activity based costing (TDABC) assigns time to events and then costs are based on the people involved in providing care for specific events. To determine the major cost drivers of radical cystectomy care we used a TDABC analysis for the cystectomy care pathway. Subjects and methods We retrospectively reviewed a random sample of 100 patients out of 717 eligible patients undergoing open radical cystectomy and ileal conduit for bladder cancer at our institution between 2012 and 2015. We defined the cycle of care as beginning at the preoperative clinic visit and ending with the 90-day postoperative clinic visit. TDABC was carried out with construction of detailed process maps. Capacity cost rates were calculated and the care cycle was divided into 3 phases: surgical, inpatient, and readmissions. Costs were normalized to the lowest cost driver within the cohort. Results The mean length of stay was 6.9 days. Total inpatient care was the main driver of cost for radical cystectomy making up 32% of the total costs. Inpatient costs were mainly driven by inpatient staff care (76%). Readmissions were responsible for 29% of costs. Surgery was 31% of the costs, with the majority derived from operating room staff costs (65%). Conclusion The major driver of cost in a radical cystectomy pathway is the inpatient stay, closely followed by operating room costs. Surgical costs, inpatient care and readmissions all remain significant sources of expense for cystectomy and efforts to reduce cystectomy costs should be focused in these areas.
Decreased platelet surface phosphatidylserine predicts increased bleeding in patients with severe factor VIII deficiency.

BACKGROUND Bleeding phenotypes among individuals with severe factor VIII (FVIII) deficiency are variable, even with routine prophylactic FVIII administration. Activated platelets, in addition to their role in primary hemostasis, play a major role in coagulation by providing a phospholipid surface to which coagulation factors bind. OBJECTIVES The aim of this study was to determine whether platelet function is associated with past and/or future bleeding in patients with severe FVIII deficiency on prophylaxis. PATIENTS/METHODS Platelet function quantified by platelet surface expression of phosphatidylserine, platelet surface glycoprotein (GP) VI, platelet surface activated GPIIb-IIIa, platelet surface P-selectin, the percentage of coated platelets, and the percentage of platelet-derived microparticles in the presence or absence of in vitro activation by various agonists was assessed in 34 patients. RESULTS Decreased platelet surface phosphatidylserine expression (identified by annexin V binding), both in the presence and absence of ADP/thrombin receptor activating peptide, demonstrated a significant association with both prior and subsequent bleeding in any location and specifically with hemarthrosis. No significant difference between patients with and without bleeding was observed in any of the other platelet activity markers. CONCLUSIONS Decreased platelet surface phosphatidylserine expression measured by annexin V binding predicts increased bleeding in severe FVIII deficient patients on prophylaxis.
Medulloblastoma-associated mutations in the DEAD-box RNA helicase DDX3X/DED1 cause specific defects in translation.

Medulloblastoma is the most common pediatric brain cancer, and sequencing studies identified frequent mutations in DDX3X, a DEAD-box RNA helicase primarily implicated in translation. Forty-two different sites were identified, suggesting that the functional effects of the mutations are complex. To investigate how these mutations are affecting DDX3X cellular function, we constructed a full set of equivalent mutant alleles in DED1, the Saccharomyces cerevisiae ortholog of DDX3X, and characterized their effects in vivo and in vitro. Most of the medulloblastoma-associated mutants in DDX3X/DED1 (ded1-mam) showed substantial growth defects, indicating that functional effects are conserved in yeast. Further, while translation was affected in some mutants, translation defects affecting bulk mRNA were neither consistent nor correlated with the growth phenotypes. Likewise, increased formation of stress granules in ded1-mam mutants was common but did not correspond to the severity of the mutants' growth defects. In contrast, defects in translating mRNAs containing secondary structure in their 5' untranslated regions (UTRs) were found in almost all ded1-mam mutants and correlated well with growth phenotypes. We thus conclude that these specific translation defects, rather than generalized effects on translation, are responsible for the observed cellular phenotypes and likely contribute to DDX3X-mutant medulloblastoma. Examination of ATPase activity and RNA binding of recombinant mutant proteins also did not reveal a consistent defect, indicating that the translation defects are derived from multiple enzymatic deficiencies. This work suggests that future studies into medulloblastoma pathology should focus on this specific translation defect, while taking into account the wide spectrum of DDX3X mutations.
Propositional and credal accuracy in an indeterministic world

It is truism that accuracy is valued. Some deem accuracy to be among the most fundamental values, perhaps the preeminent value, of inquiry. Because of this, accuracy has been the focus of two different, important programs in epistemology. The truthlikeness program (instigated by Popper) pursued the notion of propositional accuracy—an ordering of propositions by closeness to the objective truth of some matter. The epistemic utility program (instigated by Hempel) pursued the notion of credal state accuracy—an ordering of credal states by closeness to the ideal credal state. It may be tempting to think that each question that informs an inquiry must be ﻿ determinate of necessity. That is to say, there must be one correct, precise answer to it. That precise, correct answer is not only the maximally accurate answer to the question, but it also singles out the ideal credal state that is the epistemic target of the inquiry. An enormous amount of the effort has been focused on accuracy with respect to necessarily determinate questions. But often the focus of an inquiry is a question that is not necessarily determinate. Those who deem accuracy to be cognitively valuable, and fundamentally so, need an account of accuracy for indeterminate questions. Ideally such an account would cover both propositional accuracy and credal state accuracy. This is a tall order, and it is not clear that the order can be filled.