cssi/SciSciGPT-SciSciNet huggingface dataset:
Formation of Steroid-Type Skeletons: An Ubiquitous Natural Product

Steroids are one of the essential classes of bioactive compounds and are involved in many biochemical processes which include their role as signaling compounds, the alteration of membrane fluidity and the regulation of a variety of metabolic processes. In order to identify novel compounds with valuable pharmacological action, the synthesis of improved steroids is gaining much attention in recent times. Among those analogs, heterosteroids particularly azasteroids are one of the most important classes which display a variety of biological activities, often free from undesirable side effects. The challenges in the synthesis of steroids, particularly azasteroids, and the potential of azasteroids as novel drugs has prompted numerous investigations in this field. The synthetic methods leading to steroidal derivatives (azasteroids) with one or more nitrogen atoms are very limited. There are reports on the major skeletal types of steroids and their associated range of biological activities. In addition, there are increasing studies in which known non-steroidal pharmacophore are attached to the steroid skeleton with the aim that the latter might provide lipid solubility, receptor selectivity or membrane-binding properties. All these are testaments on the importance and the ubiquitous nature of steroids. The urgency for the syntheses of a wide array of steroids for several intended biomedical applications are found in the chemical and biochemical literatures. Several efforts are underway to achieve this milestone. There have been developments in therapies for the treatment of breast cancer which target the estrogen receptor. In the domain of rational drug design, a three-dimensional model of the CYP19 aromatase incorporating both the haem and the steroid substrate has been proposed.
Prehospital Factors Associated With Cervical Spine Injury in Pediatric Blunt Trauma Patients

BACKGROUND The risk for cervical spine injury (CSI) must be assessed in children who sustain blunt trauma. The Pediatric Emergency Care Applied Research Network (PECARN) retrospectively derived CSI model identifies CSI risk in children based on emergency department (ED) provider observations. The objective of this pilot study was to determine the univariate association of emergency medical services (EMS) provider-observed historical, mechanistic, and physical examination factors with CSI in injured children. Secondarily, we assessed the performance of the previously identified eight PECARN CSI risk factors (PECARN model) based exclusively on EMS provider observation. METHODS We conducted a four-center, prospective observational study of children 0 to 17 years old who were transported by EMS after blunt trauma and underwent spinal motion restriction or trauma team activation in the ED. In the ED, EMS providers recorded their observations for a priori determined CSI risk factors. CSIs were classified by reviewing imaging, consultations, and/or telephone follow-up. We calculated bivariable relative risks and test characteristics for the PECARN model based solely on EMS provider observations. RESULTS Of 1,372 enrolled children, 25 (1.8%) had CSIs. Of the a priori determined CSI risk factors, seven factors had bivariable associations with CSIs: axial load, altered mental status, signs of basilar skull fracture, substantial torso injury, substantial thoracic injury, respiratory distress, and decreased oxygen saturation. The PECARN model (high-risk motor vehicle collision, diving mechanism, predisposing condition, neck pain, decreased neck mobility, altered mental status, neurologic deficits, and/or substantial torso injury) exhibited the following test characteristics when based on EMS provider observations: sensitivity = 96.0% (95% confidence interval [CI] = 88.3% to 100.0%); negative predictive value = 99.8% (95% CI = 99.4% to 100.0%); specificity = 38.5% (95% CI = 35.9% to 41.1%); and positive predictive value = 2.8% (95% CI = 1.7% to 3.9%). CONCLUSION EMS providers can identify risk factors associated with CSI in injured children who experience blunt trauma. These risk factors may be considered for inclusion in a pediatric CSI decision rule specific to the prehospital setting.
Assessing the Role of Gay Community Attachment, Stigma, and PrEP Stereotypes on Young Men Who Have Sex with Men’s PrEP Uptake

Negative stereotypes about pre-exposure prophylaxis (PrEP) hinder PrEP uptake among young men who have sex with men (YMSM). Prior research suggests community homophobia may be linked to negative PrEP attitudes. Conversely, individuals with high gay community attachments (GCA) may have more access to credible PrEP information/resources. Among 285 YMSM recruited online, we estimated structural equation models to test competing conceptual models that inform pathways from perceived stigmas, GCA, and negative PrEP stereotype endorsements to PrEP uptake. In Model A, perceived stigma was directly associated with PrEP uptake, partially mediated by stereotype endorsement (β = − 0.05; 95% CI [− 0.09, − 0.01]) and GCA (β = − 0.06; 95% CI [− 0.11, 0.02]). In Model B, perceived stigma was associated with PrEP uptake (β = − 0.07; 95% CI [− 0.14, − 0.01]) through stereotype endorsement among high GCA YMSM. Complemented by anti-stigma initiatives, PrEP outreach for YMSM should utilize sex-positive messaging and disentangle negative PrEP stereotypes within gay-centric social spaces.
The use of strategies from the social sciences to inform pipeline development programs for under-represented minority faculty and students in the health sciences

Representation of under-represented minority (URM) faculty in the health sciences disciplines is persistently low relative to both national and student population demographics. Although some progress has been made through nationally funded pipeline development programs, demographic disparities in the various health sciences disciplines remain. As such the development of innovative interventions to help URM faculty and students overcome barriers to advancement remains a national priority. To date, the majority of pipeline development programs have focused on academic readiness, mentorship, and professional development. However, insights from the social sciences literature related to "extra-academic" (e.g., racism) barriers to URM persistence in higher education suggest the limitations of efforts exclusively focused on cognitively mediated endpoints. The purpose of this article is to synthesize findings from the social sciences literature that can inform the enhancement of URM pipeline development programs. Specifically, we highlight research related to the social, emotional, and contextual correlates of URM success in higher education including reducing social isolation, increasing engagement with research, bolstering persistence, enhancing mentoring models, and creating institutional change. Supporting URM's success in the health sciences has implications for the development of a workforce with the capacity to understand and intervene on the drivers of health inequalities.
The Reasonable Certainty Requirement in Lost Profits Litigation: What It Really Means

This article explains what courts mean when they say that lost profits must be proven with reasonable certainty. It identifies the factors that are taken into account in determining whether the plaintiff has proven its damages with sufficient certainty and explains that many of the rules that courts articulate in this area are really post hoc justifications for decisions made intuitively on the basis of the factors discussed in the article.
Coding, braiding, transmission: on the aesthetic life of dark sousveillance

Coding, Braiding, Transmission: On the Aesthetic Life of Dark Sousveillance” is a critical analysis of Tamar Clarke-Brown and Isaac Kariuki's 2017 digital startup and collaborative performance inst...
Optimizing Clinical Monitoring Tools to Enhance Patient Review by Pharmacists.

Background The Clinical Monitoring List (CML) is a real-time scoring system and intervention tool used by Mayo Clinic pharmacists caring for hospitalized patients. Objective The study aimed to describe the iterative development and implementation of pharmacist clinical monitoring tools within the electronic health record at a multicampus health system enterprise. Methods Between October 2018 and January 2019, pharmacists across the enterprise were surveyed to determine opportunities and gaps in CML functionality. Responses were received from 39% (n = 162) of actively staffing inpatient pharmacists. Survey responses identified three main gaps in CML functionality: (1) the desire for automated checklists of tasks, (2) additional rule logic closely aligning with clinical practice guidelines, and (3) the ability to dismiss and defer rules. The failure mode and effect analysis were used to assess risk areas within the CML. To address identified gaps, two A/B testing pilots were undertaken. The first pilot analyzed the effect of updated CML rule logic on pharmacist satisfaction in the domains of automated checklists and guideline alignment. The second pilot assessed the utility of a Clinical Monitoring Navigator (CMN) functioning in conjunction with the CML to display rules with selections to dismiss or defer rules until a user-specified date. The CMN is a workspace to guide clinical end user workflows; permitting the review and actions to be completed within one screen using EHR functionality. Results A total of 27 pharmacists across a broad range of practice specialties were selected for two separate two-week pilot tests. Upon pilot completion, participants were surveyed to assess the effect of updates on performance gaps. Conclusion Findings from the enterprise-wide survey and A/B pilot tests were used to inform final build decisions and planned enterprise-wide updated CML and CMN launch. This project serves as an example of the utility of end-user feedback and pilot testing to inform project decisions, optimize usability, and streamline build activities.
Knowledge Assessment in Developing/Developed Economies: Frameworks and Implementation Examples

This research in progress critically presents established methodologies recently adopted by international development institutions to assess knowledge maturity at the macro-economic level of a nation. It evaluates the advantages of specific measurement methodologies, but also contrasts the underlying assumptions of the measurement models. A more comprehensive assessment framework that integrates scorecards models with in-country workshops and culture nurturing is proposed. An example of its implementation at the country level is presented. Next steps include comparisons of the proposed methodologies with selected knowledge assessment initiatives in specific industries/organizations.
Fungal Pathogens of Plants

Fungi are the most important of the various groups of pathogens that attack plants. Our agricultural fields, forests, grasslands and urban landscapes are diminished in economic value and beauty by this important group of plant pathogens. Some fungal diseases, such as chestnut blight, make it impossible for hosts such as the American chestnut to grow where the disease is present. Keywords: plant disease; ascomycetes; basidiomycetes; rust fungi; smut fungi; disease control; host–pathogen interaction; fungal disease; disease transmission
Assessing the quality of clinical data in a computer-based record for calculating the pneumonia severity index.

Objective: This study examined whether clinical data routinely available in a computerized patient record (CPR) can be used to drive a complex guideline that supports physicians in real time and at the point of care in assessing the risk of mortality for patients with community-acquired pneumonia. Setting: Emergency department of a tertiary-care hospital. Design: Retrospective analysis with medical chart review. Patients: All 241 inpatients during a 17-month period (Jun 1995 to Nov 1996) who presented to the emergency department and had a primary discharge diagnosis of community-acquired pneumonia. Methods/Main Outcome Measures: The 20 guideline variables were extracted from the CPR (HELP System) and the paper chart. The risk score and the risk class of the Pneumonia Severity Index were computed using data from the CPR alone and from a reference standard of all data available in the paper chart and the CPR at the time of the emergency department encounters. Availability and concordance were quantified to determine data quality. The type and cause of errors were analyzed depending on the source and format of the clinical variables. Results: Of the 20 guideline variables, 12 variables were required to be present for every computer-charted emergency department patient, seven variables were required for selected patients only, and one variable was not typically available in the HELP System during a patient's encounter. The risk class was identical for 86.7 percent of the patients. The majority of patients with different risk classes were assigned too low a risk class. The risk scores were identical for 72.1 percent of the patients. The average availability was 0.99 for the data elements that were required to be present and 0.79 for the data elements that were not required to be present. The average concordance was 0.98 when all a patient's variables were taken into account. The cause of error was attributed to the nurse charting in 77 percent of the cases and to the computerized evaluation in 23 percent. The type of error originated from the free-text fields in 64 percent, from coded fields in 21 percent, from vital signs in 14 percent, and from laboratory results in 1 percent. Conclusion: From a clinical perspective, the current level of data quality in the HELP System supports the automation and the prospective evaluation of the Pneumonia Severity Index as a computerized decision support tool.
Methodological Considerations for Assessing Measures of Spontaneous Cardiac Baroreflex Sensitivity in Humans

The arterial baroreflex is a negative feedback control system that plays an important role in short-term maintenance of arterial blood pressure (BP). Analyses assessing spontaneous beat-to-beat fluctuations in BP and heart rate (HR) are increasingly being used to estimate cardiac baroreflex sensitivity. Published results have commonly used 10 min recording durations for these analyses; however, some research protocols require shorter recording durations. Since the validity of using shorter compared to longer recording durations has not been established, we tested the hypothesis that reduced baseline durations diminish the reliability of spontaneous cardiac baroreflex sensitivity measures. Beat-to-beat HR and BP were measured continuously during supine rest in 10 healthy individuals for 10 min, and spontaneous cardiac baroreflex sensitivity was estimated using the sequence technique and low frequency transfer function analysis (0.04–0.15 Hz). The 10 min baseline for each subject was divided into two 5-min ...
A phase I trial of perillyl alcohol in patients with advanced solid tumors

Perillyl alcohol is a plant-derived lipid with preclinical antitumor activity. Its proposed mechanism of action involves inhibition of post-translational isoprenylation of small G proteins, including the proto-oncogene p21-ras, thereby blocking signal transduction. This phase I trial was conducted to determine the optimal dose of perillyl alcohol. The study group comprised 21 adults with advanced solid tumors who were treated with perillyl alcohol, delivered orally, four times daily, without interruption. Doses ranged from 4,800 to 11,200 mg/m2 per day. The maximum tolerated dose (MTD) for this schedule was determined to be 8400 mg/m2 per day. The dose-limiting toxicities in this trial were nausea and vomiting, encountered in all patients at the highest dose level. No antitumor activity was observed. Pharmacokinetic data suggest dose-dependent increases in Cmax of perillic acid, a metabolite of perillyl alcohol, but with high inter- and intrapatient variability. The MTD of perillyl alcohol for this schedule was determined to be 8400 mg/m2 per day. This is higher than the MTDs determined in other similar phase I trials. This may have been due to the fact that the gastrointestinal symptoms caused by perillyl alcohol are highly subjective, with high interpatient variability. Phase II trials of perillyl alcohol in hormone-refractory prostate, breast, ovarian and colorectal cancer using doses in the range 4800–6400 mg/m2 per day are underway.
Ordered semantic hyper linking

The ordered semantic hyper-linking strategy is complete for first-order logic and accepts a user-specified natural semantics that guides the search for a proof. Any semantics in which the meanings of the function and predicate symbols are computable on ground terms may be used. This instance-based strategy is efficient on near-propositional problems, is goal sensitive, and has an extension to equality and term rewriting. However, it sometimes has difficulty generating large terms. We compare this strategy with some others that use semantic information, and present a proof of soundness and completeness. We also give some theoretical results about the search efficiency of the strategy. Some examples illustrate the performance of the strategy.
Testosterone Therapy for Female Sexual Dysfunction.

Abstract Introduction Female sexual dysfunction (FSD) is a common condition that affects 9% to 43% of the female population. Some studies have found that over 50% of women suffer from FSD. Testosterone has been prescribed to women for decades throughout the world and has more recently been used to treat women with FSD. Currently, testosterone is not FSA approved in the United States and is used off-label in women. Aim The aim of this study is to provide an overview of the current literature regarding the use of testosterone therapy (TTh) for the treatment of FSD. Methods PubMed searches through 2014 were conducted using terms “female sexual dysfunction,” “testosterone,” and “androgens.” Expert opinion was based on review of the relevant scientific and medical literature. Main Outcome Measures Treatment of FSD with TTh from peer-reviewed published literature was assessed. In addition, diagnosis, treatment options, and adverse effects of TTh were also assessed. Results The use of testosterone has been shown to improve components of FSD including sexual desire, arousal, pleasure, and overall satisfaction. While there can be adverse effects associated with TTh such as acne and hirsutism, there are no compelling data to support that TTh causes any type of cancers, such as breast cancer or endometrial cancer. Conclusion TTh appears to be safe and effective in improving FSD. Khera M. Testosterone therapy for female sexual dysfunction. Sex Med Rev 2015;3:137–144.
Impurity induced layer disordering and its importance in optoelectronic device fabrication

Summary form only given. Impurity Induced Layer Disordering (IILD) has become an established technique for the fabrication of high performance edge emitting semiconductor lasers in the AlGaAs material system. Examples of such devices are high power lasers and low threshold buried heterostructure lasers. Further, promising demonstrations have been made of the application of this technique to lateral heterojunction bipolar transistors and multiple wavelength laser arrays. In addition to the specific device applications of the IILD process, the general observation of enhanced interdiffusion in the presence of impurities has significance for many device processing technologies. For instance, in the InGaAlP/GaAs and InGaAsP/InP material systems, strain and defect generation result from non-uniform intermixing between the anion and cation lattice constituents. Resolution of these issues is desirable, as these material systems are key for laser device applications in the visible and telecommunications infrared wavelengths. The rapidly developing field of vertical cavity surface emitting lasers is following a path analogous to that of the edge emitting laser in the area of device process development. Disordering based techniques have been explored for the improvement of the performance of these devices.
A framework for comparative analysis of channel access protocols for wireless ATM networks

Enormous research interest have been expressed in merging ATM and wireless networks supporting multimedia applications. Research prototyping is currently underway at many leading research and academic institutions. Various architectures have been proposed depending on the intended application domain. One of the key components is the media access control (MAC) protocol, which has to provide support for multimedia traffic and also for quality-of-service guarantees, if required. The paper provides a comparison of previously proposed protocols, and identifies techniques proposed for supporting multimedia traffic and QoS. A preliminary comparison of the protocols based on simulation data is also presented.
Gene set bagging for estimating the probability a statistically significant result will replicate

Background Significance analysis plays a major role in identifying and ranking genes, transcription factor binding sites, DNA methylation regions, and other high-throughput features associated with illness. We propose a new approach, called gene set bagging, for measuring the probability that a gene set replicates in future studies. Gene set bagging involves resampling the original high-throughput data, performing gene-set analysis on the resampled data, and confirming that biological categories replicate in the bagged samples.
Properties of "reconstructed" motor synapses of the garter snake

We have developed a technique, called synaptic reconstruction, that permits nerve terminals of living vertebrate neuromuscular junctions (NMJs) to be isolated and then manually recombined with vacant endplate sites to form functional synapses. By reconstructing NMJs with various combinations of pre- and postsynaptic partners, or with varying degrees of pre- to postsynaptic alignment, the functional properties of the three anatomical components of the NMJ--nerve terminal, endplate, and the alignment between them--may be studied independently. Our experiments thus far indicate, surprisingly, that reconstructed NMJs function nearly normally. Thus, one feature of the intact vertebrate NMJ, precise alignment between presynaptic active zones and postsynaptic secondary folds, is either unnecessary for normal function or, alternatively, is spontaneously reestablished when an isolated terminal and vacant endplate site are placed in contact. We have also utilized synaptic reconstruction to examine a recently described property of NMJs: the regulation of quantal size among motor synapses in one muscle so that larger muscle fibers receive larger single quantal currents. Quantal size appears to be a postsynaptic attribute, suggesting that its regulation is achieved by a postsynaptic mechanism.
Fungicidal mechanisms of activated macrophages: evidence for nonoxidative mechanisms for killing of Blastomyces dermatitidis.

The mechanism(s) by which lymphokine-activated peritoneal macrophages kill Blastomyces dermatitidis was studied. Resident peritoneal macrophages from BALB/cByJ mice, when treated overnight with lymph node cells plus concanavalin A, supernatants from concanavalin A-stimulated spleen cells, or recombinant gamma interferon, were then able to kill a virulent B. dermatitidis isolate (ATCC 26199) (at levels of 25% +/- 4%, 28% +/- 8%, and 21% +/- 5%, respectively). Killing was not significantly decreased or enhanced in the presence of superoxide dismutase (450 U/ml), catalase (20,000 U/ml), dimethyl sulfoxide (300 mM), or azide (1 mM). Viable B. dermatitidis elicited a brisk oxidative burst and superoxide anion production in activated macrophages as measured by lucigenin-enhanced chemiluminescence, e.g., 10(4) cpm. However, these responses were not significantly different from those of control macrophages. Luminol-enhanced chemiluminescence responses by activated or control macrophages were meager (less than or equal to 10(2) cpm). These results indicate that activated macrophages kill B. dermatitidis by a mechanism(s) independent of products of the oxidative burst.
A comparative gradient approach as a tool for understanding and managing urban ecosystems

To meet the grand challenges of the urban century—such as climate change, biodiversity loss, and persistent poverty—urban and ecological theory must contribute to integrated frameworks that treat social and ecological dynamics as interdependent. A socio-ecological framework that encapsulates theory from the social and ecological sciences will improve understanding of metropolitan dynamics and generate science for improved, sustainable management of urban ecosystems. To date, most urban ecological research has focused on single cities. A comparative approach that uses gradients within and between cities is a useful tool for building urban ecological theory. We offer five hypotheses that are testable using a comparative, gradient approach: (i) the current size, configuration, and function of larger metropolitan ecosystems predicts the potential trajectory of smaller urban areas; (ii) timing of growth explains the greatest variance in urban ecosystem structure and function; (iii) form and function of urban ecosystems are converging over time; (iv) urban ecosystems become more segregated and fragmented as populations increase; and (v) larger cities are more innovative than smaller cities in managing urban ecosystems.
The arterial and venous anatomies of the lateral face lift flap and the SMAS.

Background:Studies of the vascularity of the superficial musculoaponeurotic system (SMAS) have suggested that it is an avascular layer. Clinical studies, however, suggest that the incidence of skin slough is higher in subcutaneous face lift dissections. A reappraisal of the arterial and venous suppl
The Gospel according to the Apostle Ben

Reconstructing or unearthing the religion of Benjamin Franklin poses quite a challenge. It is hard to reconcile his many orthodox-sounding pronouncements with the outlandish news hoaxes, loony letters to the editor, and satires in which he embeds them. This essay argues that Franklin’s special gospel is directed toward gaining self-respect and deserving it. No power, human or divine, can give that to you; it is yours to earn. This single-minded objective informs his private liturgy, his special conception of providence, his formation of the Junto, his program for moral perfection in The Art of Virtue, and his many public-spirited proposals. The artful design of his life story and the zaniness of many of the characters who populate his writings are meant to further that objective. He drew on a wide variety of modes and devices in all these cases, the better to reach and motivate a wide variety of human types.
Antecedents of B2C Channel Satisfaction and Preference: Validating e-Commerce Metrics

Although electronic commerce (EC) has created new opportunities for businesses as well as consumers, questions about consumer attitudes toward Business-to-Consumer (B2C) e-commerce vis-a-vis the conventional shopping channels continue to persist. This paper reports results of a study that measured consumer satisfaction with the EC channel through constructs prescribed by three established frameworks, namely the Technology Acceptance Model (TAM), Transaction Cost Analysis (TCA), and Service Quality (SERVQUAL). Subjects purchased similar products through conventional as well as EC channels and reported their experiences in a survey after each transaction. Using constructs from the three frameworks, a model was constructed and tested to examine the determinants of the EC channel satisfaction and preference using the survey data.Structural equation model analyses indicate that metrics tested through each model provide a statistically significant explanation of the variation in the EC consumers' satisfaction and channel preference. The study found that TAM components--perceived ease of use and usefulness--are important in forming consumer attitudes and satisfaction with the EC channel. Ease of use also was found to be a signi.cant determinant of satisfaction in TCA. The study found empirical support for the assurance dimension of SERVQUAL as determinant in EC channel satisfaction. Further, the study also found general support for consumer satisfaction as a determinant of channel preference.
On the kinking nonlinear elastic deformation of cobalt

Abstract Recently cobalt was classified as a kinking nonlinear elastic, KNE, solid. Fully reversible incipient kink bands, IKBs, were invoked to explain both its microyielding and hysteretic stress–strain curves. Herein we present further evidence and insights in the KNE nature of cobalt by measuring its mechanical hysteresis as a function of grain size, pre-strain and testing temperature. Unlike previous work, in coarse-grained cobalt, something other than grain boundaries determine the domain size. The hysteresis loops were only obtained at temperatures where cobalt was hexagonal-close packed. In situ neutron diffraction strains could only account for ≈1/3 of the total strain measured and ruled out dislocation pileups as the source of the remaining strain suggesting that it is due to IKBs. The totality of our results can be successfully explained and quantified by our microscale IKB-based model, based on which we estimate the critical resolved shear stress of basal plane dislocations to be 13 ± 3 MPa and the reversible dislocation density to be 1.5–6 × 10 13 m −2 in the ≈200–400 MPa stress range.
The Effects of Perceived Supervisor Support, Perceived Organizational Support, and Organizational Justice on Turnover among Salespeople

This study examined effects of three dimensions of organizational justice on salesperson perceived organizational support (POS), perceived supervisor support (PSS), performance, and actual salesperson turnover in a business-to-business setting using a sample of 384 salespeople. Results indicated that PSS is an indirect predictor of turnover intentions through POS and performance. Organizational commitment mediated the relationship between POS and turnover intentions. Procedural justice had a direct, positive influence on performance. Distributive justice, procedural justice, and interactional justice were indirect predictors of turnover through other variables. The salesperson’s performance was related directly to both turnover intentions and turnover.
5-Fluorouracil by Protracted Venous Infusion: A Review of Recent Clinical Studies

AbstractThe pharmacokinetics of continuous infusion 5-fluorouracil make it an ideal drug to administer as a protracted infusion (continuous infusion more than 30 days). During the last decade numerous clinical studies have been conducted to evaluate the efficacy of 5-fluorouracil (5FU) administered as a protracted venous infusion. Phase II studies in metastatic colorectal cancer in 345 patients have demonstrated an average response rate of 36% (range 15-59%) and a prospective randomized study performed by the Mid-Atlantic Oncology Program (MAOP) has confirmed a higher response rate with 5FU infusion compared with a bolus schedule. Phase II studies in refractory carcinoma of the breast in 177patients have demonstrated a 30% response rate (range 17-50%); studies in pancreatic, gastric, and refractory prostate cancer have also demonstrated clinical utility. The major toxicities of 5FU infusion are mucositis and hand-foot syndrome; life-threatening myelosuppression is rare and treatment-related deaths have no...
Representer-based analyses in the coastal upwelling system

Abstract The impact of surface velocity and SSH data assimilated in a model of wind-driven upwelling over the shelf is studied using representer and observational array mode analyses and twin experiments, utilizing new tangent linear (TL) and adjoint (ADJ) codes. Bathymetry, forcing, and initial conditions are assumed to be alongshore uniform reducing the problem to classical two-dimensional. The model error is attributed to uncertainty in the surface wind stress. The representers, analyzed in cross-shore sections, show how assimilated observations provide corrections to the wind stress and circulation fields, and give information on the structure of the multivariate prior model error covariance. Since these error covariance fields satisfy the dynamics of the TL model, they maintain dominant balances (Ekman transport, geostrophy, thermal wind). Solutions computed over a flat bottom are qualitatively similar to a known analytical solution. Representers obtained with long cross-shore decorrelation scale for the wind stress errors l x (compared to the distance to coast) exhibit the classical upwelling structure. Solutions obtained with much smaller l x show structure associated with Ekman pumping, and are nearly singular if l x is smaller than the grid resolution. The zones of maximum influence of observations are sensitive to the background ocean conditions and are not necessarily centered around the observation locations. Array mode analysis is utilized to obtain model structures (combinations of representers) that are most stably observed by a given array. This analysis reveals that for realistic measurement errors and observational configurations, surface velocities will be more effective than SSH in providing correction to the wind stress on the scales of tens of km. In the DA test with synthetic observations, the prior nonlinear solution is obtained with spatially uniform alongshore wind stress and the true solution with the wind stress sharply reduced inshore of the upwelling front, simulating expected ocean–atmosphere interaction. Assimilation of daily-averaged alongshore surface currents provides improvement to both the wind stress and circulation fields.
Density driven self‐consistent field method. II. construction of all one‐particle wavefunctions that are orthonormal and sum up to a given density

In Part I of the series we formulated the density driven self-consistent field method. In the present communication we rigorously prove the existence of the generalized overlap matrix and demonstrate some of its properties.
Nutritional state modulates hormone-mediated hepatic glycogenolysis in chinook salmon (Oncorhynchus tshawytscha)

Juvenile chinook salmon were used to investigate the interaction of nutritional state and hormones (glucagon, epinephrine) on hepatic glycogenolysis. Experiments were conducted in vitro on liver removed from animals of varying nutritional states: fed 1 week, fasted 1 week, fed 3 weeks, fasted 3 weeks, and fasted 1 week/refed 2 weeks. Basal glycogen breakdown in liver isolated from continuously fed (1 week and 3 weeks) fish proceeded at insignificant levels, whereas glycogen breakdown in liver isolated from fasted animals progressed rapidly during the course of incubation. However, no difference in the pattern of glycogen breakdown between liver isolated from animals fasted for 1 week and those fasted for 3 weeks was observed. The presence of glucose in the incubation medium retarded glycogen breakdown in the livers from fasted fish. Both epinephrine and glucagon stimulated glucose release from liver isolated from fish fed continuously and from fish fasted 1 week; epinephrine appeared more potent in this regard than glucagon. Epinephrine also stimulated glucose release from liver isolated from fish fasted 3 weeks, whereas glucagon was without significant glycogenolytic effect on this tissue. Insulin inhibited epinephrine- and glucagon-stimuluated glucose release. These results suggest that glucagon plays a role in modulating nutrition-associated adjustments in metabolism during the early stages of fasting and that, with extended fasting, the liver loses its sensitivity to glucagon with regard to glycogenolysis.
Chemotransduction by carotid body chemoreceptors is dependent on bicarbonate currents.

Abstract Previous studies have demonstrated that bicarbonate enhances the speed and magnitude of the carotid body chemoreceptor response to hypoxia. We hypothesized that this enhancement is associated with enhanced hypoxia-induced catecholamine (CAT) secretion from glomus cells. Single-fiber nerve activity and free tissue catecholamine (carbon fiber microvoltammetry) were measured in rat carotid body, in vitro. The peak CAT and nerve responses during 1 min anoxia were larger in the presence of bicarbonate than in its absence (peak CAT: 16.7±2.7 vs. 5.1±1.1 μM; peak nerve: 28.2±1.6 vs. 16.7±1.4 Hz). Bicarbonate particularly enhanced the responses to moderate hypoxia (PO2∼80 Torr) which caused no secretion or increased nerve activity in the absence of bicarbonate, but caused significant stimulation in the presence of bicarbonate (peak nerve=15.2 Hz; peak CAT=8.6 μM). The bicarbonate effect was not due to alterations in intracellular pH since it was not blocked by exchanger blockers (DIDS) or mimicked by acidification of the medium. However, anion channel blockade by 9-AC or DPC reduced anoxia-induced CAT secretion in the presence of bicarbonate. We conclude that bicarbonate greatly enhances stimulus/secretion coupling in glomus cells, probably through modulation of an anion current carried by bicarbonate.
Genome of a songbird unveiled

An international collaborative effort has recently uncovered the genome of the zebra finch, a songbird model that has provided unique insights into an array of biological phenomena.
Regenerative oil scrubbing of volatile organic compounds from a gas stream in hollow fiber membrane devices

A regenerative membrane-based absorption process has been extensively studied to remove volatile organic compounds (VOCs) from air/N2 using silicone oil as the absorbent. The absorbent liquid is regenerated by applying a vacuum in a membrane-based stripper. In this process, there are no flooding, loading, and entrainment, which limit the gas/liquid flow rate in the traditional absorption process. In the present study, attention has been focused on the removal of volatile component(s) from binary gas mixtures such as methanol−N2 and toluene−N2 and from a model multicomponent mixture of gasoline vapor constituents and nitrogen. The process performance was tested under three conditions: (i) absorption with fresh absorbent; (ii) absorption and stripping modules at the same (room) temperature; (iii) maintaining different temperatures in the absorption and stripping modules. Henry's law constants and diffusivities of VOCs in silicone oil needed to simulate the process performances have been experimentally meas...
Clinical utility of atypical glandular cells (agc) classification: cytohistologic comparison and relationship to hpv results

Abstract Objectives. To determine the utility of the category of atypical glandular cells (AGC) in the management of patients with putative cervical neoplasia and to correlate HPV-DNA test results when available. Methods. The Johns Hopkins Hospital cytopathology records of 50,668 women patients were searched for all liquid-based gynecologic cytology (LBP) results of Atypical Glandular cells of Undetermined Significance (AGUS) and AGC from January 1, 2001 through December 31, 2003, yielding 98 patients (0.19%). Oncogenic HPV-DNA tests were performed on the residual fluids of 43 of these patients, 37 of whom had follow-up biopsy. During the period of January 1, 2000 and December 31, 2002, we identified 237 patients (0.58%) with conventional Pap smears in the AGUS or AGC category, among 41,024 conventional smears collected contemporaneously. To avoid confusion in this paper, AGC will be used to replace those results that originally were AGUS. Results. Following the 98 LBP AGC interpretations, 24 lesions (33.8%) were discovered out of 71 biopsies. HPV-DNA tests were performed on the residual of 43 LBPs, 18 (41.9%) were positive for oncogenic HPV. Only 37 patients had follow-up biopsy and 15 (40.5%) were positive for oncogenic HPV, of which 40% (6/15) had a significant lesion. Of the 237 conventional AGC Paps, 18 lesions (15.3%) were discovered out of 118 biopsies. Conclusions. Comparison of liquid-based and conventional Pap tests revealed a significant difference (33.8% vs. 15.3% respectively) (OR: 2.84, 95% CI: 1.4–5.73, p =0.004) in the detection of glandular and squamous lesions. HPV testing may prove beneficial to triage AGC patients with negative colposcopic findings and positive HPV results.
Erythema multiforme major following treatment with infliximab

Background The growth in the use of anti–tumor necrosis factor α (TNF-α) agents for treatment of inflammatory conditions has led to increased recognition of the side effects associated with this class of drugs. Case description We report a case of a patient who developed erythema multiforme (EM) major with characteristic oral and cutaneous lesions following treatment with the anti-TNF-α medication infliximab therapy for Crohn's disease (CD). Clinical implications To our knowledge, this is the first reported case of infliximab-induced EM secondary to the treatment of CD. It is important for dental clinicians evaluating patients using anti-TNF-α agents to be aware of this possible complication.
Human Colonic Myoelectric Activity in Response to Prostigmin and the Gastrointestinal Hormones

Colonic myoelectric activity was determined using a mucosal clip electrode in normal human subjects, in the basal state and following the administration of prostigmin, pentagastrin, cholecystokinin, or secretin. Slow-wave activity was present 49±3.0% of the recording time and occurred at two frequencies, 6.5±0.1 cycles/min and 3.5±0.1 cycles/min, in the rectum. Spike potentials were infrequent in the basal state. Prostigmin, pentagastrin, or cholecystokinin did not affect the slow-wave activity or frequency, but these agents significantly increased the number of spike potentials (P<0.05). Secretin had no effect on myoelectric activity. The electrode system was tested in the cat and showed excellent correlation of the myoelectric activity between the mucosal clip electrode and a serosal electrode. These studies indicate: (1) a mucosal clip electrode provides an accurate method of recording colonic myoelectric activity when compared to a serosal electrode in the cat; (2) in man, slow-wave activity is present only intermittently and exists at two frequencies, approximately 6 cycles/min and 3 cycles/min; (3) gastrointestinal hormones and prostigmin increase spike potential discharge without altering slow-wave activity or frequency.
A smoothed boosting algorithm using probabilistic output codes

AdaBoost.OC has shown to be an effective method in boosting "weak" binary classifiers for multi-class learning. It employs the Error Correcting Output Code (ECOC) method to convert a multi-class learning problem into a set of binary classification problems, and applies the AdaBoost algorithm to solve them efficiently. In this paper, we propose a new boosting algorithm that improves the AdaBoost.OC algorithm in two aspects: 1) It introduces a smoothing mechanism into the boosting algorithm to alleviate the potential overfitting problem with the AdaBoost algorithm, and 2) It introduces a probabilistic coding scheme to generate binary codes for multiple classes such that training errors can be efficiently reduced. Empirical studies with seven UCI datasets have indicated that the proposed boosting algorithm is more robust and effective than the AdaBoost.OC algorithm for multi-class learning.
Smoluchowski Equation Description of Solute Diffusion Dynamics and Time-Dependent Fluorescence in Nanoconfined Solvents

The diffusion dynamics and time-dependent fluorescence of a model dye molecule dissolved in CH3I, CH3CN, and CH3OH solvents confined in nanoscale cavities and pores of 20−30 A diameter have been modeled using a Smoluchowski equation approach. The effects of the confining framework geometry (spherical or cylindrical) and size have been investigated. The two-degree-of-freedom free-energy surfaces for the dye molecule ground and excited states are constructed from one-dimensional free-energy curves in the solute position and model force constants for a collective solvent coordinate. Multiple time scales are found in the solute diffusion after excitation and in the time-dependent fluorescence. The origins of these time scales can be understood in terms of solvent reorganization and dye molecule diffusion. The results indicate that the Smoluchowski equation approach has promise for describing time-dependent fluorescence dynamics, and ultimately reaction dynamics, in a wide variety of confined solvent systems.
Alterations in regional cerebral blood flow in neonatal stroke: preliminary findings with color Doppler sonography

Little information is available regarding alterations in regional cerebral blood flow and vascularity on cranial sonography in infants with focal ischemic brain injury. This study describes the use of color Doppler sonography in the characterization of these changes following acute neonatal stroke. Color Doppler examinations were performed as part of the series of clinically indicated cranial sonograms in eight infants with clinical, sonographic, and CT evidence of acute cerebral infarction. The cerebral vascularity of each hemisphere was assessed for symmetry and for presence of abnormal blood vessels. Initial Doppler study in four infants with hypoxic-ischemic infarcts showed increased size and number of visible vessels in the periphery of the infarct and increased mean blood flow velocity in vessels supplying or draining the infarcted areas. Diminished vessel number and size and frequency shifts suggestive of decreased hemispheric perfusion was identified in one infant with middle cerebral artery insufficiency. Repeat Doppler studies were performed on two infants. These showed the development of multiple small, irregular blood vessels in the periphery of the infarct. Focal abnormalities in regional cerebral blood flow may be present as part of the normal healing process following neonatal stroke, and can be demonstrated with color Doppler sonography.
Postplacental insertion of the levonorgestrel intrauterine device after cesarean delivery vs. delayed insertion: a randomized controlled trial ☆ ☆☆ ★

Objective: This trial was designed to compare levonorgestrel intrauterine device (LNG-IUD) use at 1 year after delivery between women randomized to postplacental insertion at the time of cesarean delivery and delayed insertion 4-8 weeks after delivery. Study design: This randomized controlled trial was conducted at two urban medical centers. Eligible pregnant women with planned cesarean deliveries were randomized to immediate postplacental insertion during cesarean or delayed insertion after 4-8 weeks. We used intention-to-treat analysis for the primary outcome of LNG-IUD use 12 months after delivery. Results: Forty-two women were randomized 20 into the postplacental group and 22 in the delayed group. Although confirmed use of the LNG-IUD 12 months after delivery was higher in the postplacental group (60.0% vs. 40.9% p=.35) this difference was not statistically significance. Expulsion was significantly more common in the postplacental group (20.0% vs. 0% p=.04). There were significant differences between the two sites in baseline population characteristics follow-up and expulsion. The trial did not answer the intended question as it was halted early due to slow enrollment. Conclusions: Our results show higher expulsion after postplacental insertion compared to delayed insertion but suggest similar IUD use at 12 months. Moreover it provides valuable lessons regarding a randomized controlled trial of postplacental LNG-IUD placement due to the challenges of estimating effect size and the nature of the population who might benefit from immediate insertion. Implications: Postplacental insertion of an IUD may improve use of highly effective contraception during the postpartum period. While our results suggest higher expulsion after postplacental insertion compared to delayed insertion and similar IUD use at 12 months our trial was insufficient to definitively test our hypothesis. Copyright © 2014 Elsevier Inc. All rights reserved.