cssi/SciSciGPT-SciSciNet huggingface dataset:
Tumor-Nipple Distance of ≥ 1 cm Predicts Negative Nipple Pathology After Neoadjuvant Chemotherapy

As neoadjuvant chemotherapy (NAC) for breast cancer has become more widely used, so has nipple-sparing mastectomy. A common criterion for eligibility is a 1 cm tumor-to-nipple distance (TND), but its suitability after NAC is unclear. In this study, we examined factors predictive of negative nipple pathologic status (NS−) in women undergoing total mastectomy after NAC. Women with invasive breast cancer treated with NAC and total mastectomy from August 2014 to April 2018 at our institution were retrospectively identified. Following review of pre- and post-NAC magnetic resonance imaging (MRI) and mammograms, the association of clinicopathologic and imaging variables with NS− was examined and the accuracy of 1 cm TND on imaging for predicting NS− was determined. Among 175 women undergoing 179 mastectomies, 74% of tumors were cT1-T2 and 67% were cN+ on pre-NAC staging; 10% (18/179) had invasive or in situ carcinoma in the nipple on final pathology. On multivariable analysis, after adjusting for age, grade, and tumor stage, three factors, namely number of positive nodes, pre-NAC nipple-areolar complex retraction, and decreasing TND, were significant predictors of nipple involvement (p < 0.05). The likelihood of NS− was higher with increasing TND on pre- and post-NAC imaging (p < 0.05). TND ≥ 1 cm predicted NS− in 97% and 95% of breasts on pre- and post-NAC imaging, respectively. Increasing TND was associated with a higher likelihood of NS−. A TND ≥ 1 cm on pre- or post-NAC imaging is highly predictive of NS− and could be used to determine eligibility for nipple-sparing mastectomy after NAC.
Reduced preload increases Mechanical Control (strain-rate dependence) of Relaxation by modifying myosin kinetics

Rapid myocardial relaxation is essential in maintaining cardiac output, and impaired relaxation is an early indicator of diastolic dysfunction. While the biochemical modifiers of relaxation are well known to include calcium handling, thin filament activation, and myosin kinetics, biophysical and biomechanical modifiers can also alter relaxation. We have previously shown that the relaxation rate is increased by an increasing strain rate, not a reduction in afterload. The slope of the relaxation rate to strain rate relationship defines Mechanical Control of Relaxation (MCR). To investigate MCR further, we performed in vitro experiments and computational modeling of preload-adjustment using intact rat cardiac trabeculae. Trabeculae studies are often performed using isometric (fixed-end) muscles at optimal length (Lo, length producing maximal developed force). We determined that reducing muscle length from Lo increased MCR by 20%, meaning that reducing preload could substantially increase the sensitivity of the relaxation rate to the strain rate. We subsequently used computational modeling to predict mechanisms that might underlie this preload-dependence. Computational modeling was not able to fully replicate experimental data, but suggested that thin-filament properties are not sufficient to explain preload-dependence of MCR because the model required the thin-filament to become more activated at reduced preloads. The models suggested that myosin kinetics may underlie the increase in MCR at reduced preload, an effect that can be enhanced by force-dependence. Relaxation can be modified and enhanced by reduced preload. Computational modeling implicates myosin-based targets for treatment of diastolic dysfunction, but further model refinements are needed to fully replicate experimental data.
Utilization of Point-of-care Echocardiography in Cardiac Arrest: A Cross-sectional Pilot Study

Introduction: Point-of-care (POC) echocardiography (echo) is a useful adjunct in the management of cardiac arrest. However, the practice pattern of POC echo utilization during management of cardiac arrest cases among emergency physicians (EP) is unclear. In this pilot study we aimed to characterize the utilization of POC echo and the potential barriers to its use in the management of cardiac arrest among EPs. Methods: This was a cross-sectional survey of attending EPs who completed an electronic questionnaire composed of demographic variables (age, gender, year of residency graduation, practice setting, and ultrasound training) and POC echo utilization questions. The first question queried participants regarding frequency of POC echo use during the management of cardiac arrest. Branching logic then presented participants with a series of subsequent questions regarding utilization and barriers to use based on their responses. Results: A total of 155 EPs participated in the survey, with a median age of 39 years (interquartile range 31-67). Regarding POC echo utilization, participants responded that they always (66%), sometimes (30%), or never (4.5%) use POC echo during cardiac arrest cases. Among participants who never use POC echo, 86% reported a lack of training, competency, or credentialing as a barrier to use. Among participants who either never or sometimes use POC echo, the leading barrier to use (58%) reported was a need for improved competency. Utilization was not different among participants of different age groups (P = 0.229) or different residency graduation dates (P = 0.229). POC echo utilization was higher among participants who received ultrasound training during residency (P = 0.006) or had completed ultrasound fellowship training (P <0.001) but did not differ by gender (P = 0.232), or practice setting (0.231). Conclusion: Only a small minority of EPs never use point-of-care echocardiography during the management of cardiac arrest. Lack of training, competency, or credentialing is reported as the leading barrier to use among those who do not use POC echo during cardiac arrest cases. Participants who do not always use ultrasound are less likely to have received ultrasound training during residency.
Targeted Disruption of the Inhibitor of DNA Binding 4 (Id4) Gene Alters Photic Entrainment of the Circadian Clock.

Inhibitor of DNA binding (Id) genes comprise a family of four helix–loop–helix (HLH) transcriptional inhibitors. Our earlier studies revealed a role for ID2 within the circadian system, contributing to input, output, and core clock function through its interaction with CLOCK and BMAL1. Here, we explore the contribution of ID4 to the circadian system using a targeted disruption of the Id4 gene. Attributes of the circadian clock were assessed by monitoring the locomotor activity of Id4−/− mice, and they revealed disturbances in its operation. Id4-mutant mice expressed a shorter circadian period length, attenuated phase shifts in responses to continuous and discrete photic cues, and an advanced phase angle of entrainment under a 12:12 light:dark cycle and under short and long photoperiods. To understand the basis for these properties, suprachiasmatic nucleus (SCN) and retinal structures were examined. Anatomical analysis reveals a smaller Id4−/− SCN in the width dimension, which is a finding consistent with its smaller brain. As a result of this feature, anterograde tracing in Id4−/− mice revealed retinal afferents innovate a disproportionally larger SCN area. The Id4−/− photic entrainment responses are unlikely to be due to an impaired function of the retinal pathways since Id4−/− retinal anatomy and function tested by pupillometry were similar to wild-type mice. Furthermore, these circadian characteristics are opposite to those exhibited by the Id2−/− mouse, suggesting an opposing influence of the ID4 protein within the circadian system; or, the absence of ID4 results in changes in the expression or activity of other members of the Id gene family. Expression analysis of the Id genes within the Id4−/− SCN revealed a time-of-day specific elevated Id1. It is plausible that the increased Id1 and/or absence of ID4 result in changes in interactions with bHLH canonical clock components or with targets upstream and/or downstream of the clock, thereby resulting in abnormal properties of the circadian clock and its entrainment.
A Multigraph-Based Method for Improving Music Recommendation

Music recommendation systems have become an important part of the user-centric online music listening experience. However, current automated systems often are not tuned for exploiting the full diversity of a song catalogue, and consequently, discovering new music requires considerable user effort. Another issue is current implementations generally require significant artist metadata, user listening history, or a combination of the two, to generate relevant recommendations. To address the problems with traditional recommendation systems, we propose to represent artist-to-artist relationships as both simple multigraphs and more complicated multidimensional networks. Using data gathered from the MusicBrainz open music encyclopedia, we demonstrate our artist-based networks are capable of producing more diverse and relevant artist recommendations.
On Postmodernist Feminist Legal Theory

This Article seeks to chart and evaluate postmodern interventions in feminist legal theory and to suggest ways that postmodern insights could more effectively further feminist legal theory's normative commitment to end sexual oppression. In Part I, I discuss feminist legal scholars' appropriation of postmodern conceptions of power as discourse, and how these scholars have related these conceptions to gender hierarchy. In Part II, I consider the trend in feminist legal theory against generalizations based on gender, and the related drive toward a politics of diversity and multiplicity that has been spurred by postmodern insights. In Part III, I discuss the ways in which feminist legal theorists have sought to convert postmodern insights into positive feminist legal projects. In each of these three areas, I argue that although postmodernism offers valuable insights, its application to date demonstrates corresponding weaknesses that undermine the goals of feminist legal theory. Specifically, postmodernist legal scholars have repeatedly failed to treat postmodern strivings for heterogeneity, multiplicity, and difference as ends that must be achieved through ongoing political and legal struggle. Instead, they have generally treated these goals as if they were either already achieved or, alternatively, as if they could be accomplished through theoretical fiat. As a result, postmodern feminist legal theory has failed to develop a rigorous analysis of what kind of legal systems and legal measures will best foster the reinterpretation of dominant discourses and the subversion of traditional gender identities they seek to promote. In Part IV, I conclude by offering a constructive view of the way in which postmodernist insights could better further the goals of feminist legal theory, an approach that seeks to overcome the limitations of postmodern feminism to date.
Educational evaluation in China: An analysis of current practices☆

Abstract The Chinese educational system is being challenged to play a pivotal role in the four modernizations. In recent years much effort has been put into educational reform, but much remains to be done. The intent of this article is to discuss the role that evaluation can play in the improvement of the Chinese education system. Although it is claimed frequently that evaluation is a new topic in China, it is more accurate to say that the jargon or language may be new and that various types of evaluation have been and are being conducted at all levels of the Chinese educational system. Results from a recent survey and case studies of evaluation practices in primary and secondary schools in Shanghai will be described to justify this view. The importance of blending present practices with approaches from the West also will be highlighted. The article will conclude with a description of current developments in educational evaluation in China.
SPECT reconstruction using uniform and object-specific attenuation maps with emission-transmission CT

A prototype emission-transmission computed tomographic (ETCT) system was used to acquire both radionuclide-emission and dual-energy X-ray transmission data of a thorax-like phantom. An object- and energy-specific attenuation map was synthesized from the dual-energy X-ray data, and then incorporated into a maximum likelihood-expectation maximization (ML-EM) algorithm to reconstruct an attenuation-corrected single photon emission computed tomography (SPECT) image. SPECT images reconstructed with no attenuation correction, or with a uniform water-equivalent map, contained increased count levels in the lung region and reduced count levels in the cardiac region as compared to the radioactivity concentrations contained in the phantom. Correction with an object-specific attenuation map improved the accuracy of the reconstruction, but overestimated the activity in the cardiac chamber by about 10%. >
Efficient Path Selection for Delay Testing Based on Path Clustering

In this paper, we introduce a way of modeling the differences between the calculated delays and the real delays, and propose an efficient path selection method for path delay testing based on the model. Path selection is done by judging which of two paths has the larger real delay by taking into account the ambiguity of calculated delay, caused by imprecise delay modeling as well as process disturbances. In order to make precise judgment under this ambiguity, the delays of only the unshared segments of the two paths are evaluated. This is because the shared segments are presumed to have the same real delays on both paths. The experiments used the delays of gates and interconnects, which were calculated from the layout data of ISCAS85 benchmark circuits using a real cell library. Experimental results show the method selects only about one percent of the paths selected by the most popular method.
Efficient Checking of Polynomials and Proofs and the Hardness of Approximation Problems

The definition of the class NP (Coo71, Lev73) highlights the problem of verification of proofs as one of central interest to theoretical computer science. Recent efforts have shown that the efficiency of the verification can be greatly improved by allowing the verifier access to random bits and accepting probabilistic guarantees from the verifier (BFL91, BFLS91, FGL$\sp+$91, AS92). We improve upon the efficiency of the proof systems developed above and obtain proofs which can be verified probabilistically by examining only a constant number of (randomly chosen) bits of the proof. The efficiently verifiable proofs constructed here rely on the structural properties of low-degree polynomials. We explore the properties of these functions by examining some simple and basic questions about them. We consider questions of the form: (1) (testing) Given an oracle for a function f, is f close to a low-degree polynomial? (2) (correcting) Let f be close to a low-degree polynomial g, is it possible to efficiently reconstruct the value of g on any given input using an oracle for f? The questions described above have been raised before in the context of coding theory as the problems of error-detecting and error-correcting of codes. More recently interest in such questions has been regenerated due to its connections with the area of program result checking. We use results from coding theory as a starting point and combine these with several algorithmic techniques including pairwise independent sampling to give efficient randomized algorithms for these tasks. As a consequence we obtain fast randomized algorithms for error-detection and error-correction for some well-known codes. The expressive nature of low-degree polynomials suffices to capture the complexity of the class NP and we translate our results on the efficiency of the testing and correcting procedures into two different efficiently verifiable proof systems for deciding membership questions for NP languages. One proof system generates small and somewhat efficiently verifiable proofs and the other generates very large but very efficiently verifiable proofs. We then employ new techniques from the paper of (AS92) to compose these proof systems to obtain small proofs which can be verified by probing them in just a constant number of (randomly chosen) bits. An important consequence of this result is that for a large class of NP-complete optimization problems, it can be shown that finding even approximate solutions is an NP-hard problem. The particular class of optimization problems we consider is MAX SNP, introduced by Papadimiatriou and Yannakakis (PY91). For every MAX SNP-hard problem we show that there is a constant $\epsilon$, such that approximating the optimum to within a relative error of $\epsilon$ is NP-hard.
Gene trapping methods for the identification and functional analysis of cell surface proteins in mice.

Publisher Summary Gene trapping offers an alternative method to create random insertional mutations that are immediately accessible to molecular characterization. By eliminating the time-consuming step of constructing targeting vectors for each gene of interest, the rate at which new mutations may be introduced in the germ line by gene trapping far exceeds that of conventional gene targeting. Thus, gene trapping represents a rapid and cost-efficient method for the identification and functional analysis of new genes in mice. Gene trap vectors are activated through the production of a reporter gene fusion transcript following insertions of the vector within endogenous transcription units. Given the time and resources required for the phenotypic analysis of mutant mice, it is advantageous to tailor screens toward specific genes of interest. A variety of criteria may be used to preselect insertional mutants prior to germ line transmission and phenotype analysis. These include the sequence of the target gene, the expression profile of the target gene, and the subcellular localization of the fusion product. This chapter focuses on a strategy developed to select insertional mutations specifically in genes encoding cell surface proteins based on the subcellular localization of the fusion protein products in embryonic stem (ES) cells. An overview of this technology is presented in the chapter followed by a detailed description of the experimental procedures.
Percutaneous endoscopic gastrostomy tube dependence following chemoradiation in head and neck cancer patients.

Objectives/Hypothesis Compare long-term percutaneous endoscopic gastrostomy (PEG) tube dependence, stricture rate, and weight loss in patients receiving a prophylactic gastrostomy tube with those who initially rely on oral intake during chemoradiation for head and neck cancer. Also, to determine what other patient and treatment characteristics influence development of long-term severe dysphagia. Study Design Retrospective review. Methods Seventy-nine patients received a PEG tube and 25 did not. The prophylactic and initial oral intake groups were then analyzed to assess the primary outcomes of PEG dependence at last follow-up >1 year. Results On univariate and multivariate analysis, Zubrod score >1, prophylactic PEG placement, and higher T classification were predicted for PEG tube dependence at last follow-up at least 1 year after treatment. Conclusions Prophylactic PEG tube, high Zubrod score, and high T stage were independent predictors for PEG tube dependence at least 1 year after treatment in patients with head and neck cancer receiving definitive chemoradiation. Level of Evidence 4 Laryngoscope, 125:1366–1371, 2015
RESEARCH AND DEVELOPMENT OF ARMS

Military RD and the problem of the long-range effects of new weapons technology on international stability.
Innovation by acquisition

Innovation by acquisition is an increasingly important strategy for innovation in established high technology firms. After describing the background for innovation in small and large firms, a model for innovation by acquisition and the roles of established firms, entrepreneurial firms, and investors is developed, and evidence presented suggesting increasing application of the model.
Images of commuting differential operators of order one with constant leading coefficients

Abstract We first study some properties of images of commuting differential operators of polynomial algebras of order one with constant leading coefficients. We then propose what we call the image conjecture on these differential operators and show that the Jacobian conjecture (Bass et al. (1982) [BCW] , van den Essen (2000) [E] , de Bondt (2009) [Bo] ) (hence also the Dixmier conjecture (Dixmier (1968) [D] )) and the vanishing conjecture (Zhao (2007) [Z3] ) of differential operators with constant coefficients are actually equivalent to certain special cases of the image conjecture. A connection of the image conjecture, and hence also the Jacobian conjecture, with multidimensional Laplace transformations of polynomials is also discussed.
Electrochemical Light, From Laboratory Curiosity to Useful Analytical Technique

Electrochemiluminescence (ECL) is the process where species generated at electrodes undergo electron-transfer reactions to form excited states that emit light. Application of a voltage to an electrode in the presence of an ECL luminophore such as Ru(bpy)32+ (where bpy = 2,2′-bipyridine) or diphenylanthracene results in light emission and allows detection of the emitter at very low concentrations (≤10−12 mol dm−3). By employing ECL-active species as labels on biological molecules, ECL has found commercial application for immunoassays and DNA analyses. The history of ECL is presented including the earliest, curiosity driven experiments and the development of ECL into an analytical technique for clinical diagnostic applications. The development and use of ECL sensors is an excellent example of how, over time, a laboratory curiosity can become a useful, powerful, and commercially viable technique.
Crack deflection processes—II. Experiment

Two microstructural characteristics, particle morphology and size, have been examined with respect to toughening by crack deflection. Particle morphology effects were evaluated in a series of hot-pressed silicon nitrides comprised of rod-shaped grains of various aspect ratios and a bariumsilicate glass ceramic containing spherulites. Lithium-alumino-silicate glass ceramics containing Li_2Si_2O_5 lath-shaped crystals were studied for particle size effects. Independent measures of the fracture toughness and the crack deflection process were performed and results were correlated with a crack deflection model.
Mutational analysis of the fingers and palm subdomains of human immunodeficiency virus type-1 (HIV-1) reverse transcriptase.

We have analyzed the human immunodeficiency virus type-1 reverse transcriptase (HIV-1 RT) polymerase domain between amino acids 91 and 157 by site-directed mutagenesis. We have constructed a series of amino acid substitutions using BspMI cassettes, and have assayed the RNA-dependent DNA polymerase, DNA-dependent DNA polymerase, and Rnase H activities of the mutant HIV-1 RTs. The regions of HIV-1 RT between amino acids 91 and 119 between amino acids 151 and 157 lie within the palm subdomain and include part of the polymerase active site. A number of amino acids within these regions have been identified as being directly or indirectly involved with polymerization, since amino acid substitutions at these residues decrease the polymerase activity without affecting Rnase H activity. The region of HIV-1 RT between amino acids 120 and 150 lies within the fingers subdomain of the HIV-1 polymerase. We believe that the fingers subdomain plays a role in positioning the template. Many amino acid substitutions in this region decrease or abolish both the polymerase and the Rnase H functions.
Pulmonary clearance of Staphylococcus aureus and plasma angiotensin-converting enzyme activity in hydrocarbon pneumonitis.

Summary: Pulmonary clearance of Staphylococcus aureus and plasma angiotensin-converting enzyme (ACE) activity were investigated in an experimental mouse model of kerosene aspiration. Twenty-four hours after acute kerosene aspiration, mice were exposed for 30 min to an aerosol containing the pathogen, and the uncleared bacteria ratio (UBR) determined 4 h after nebulization. The results showed a significant increase (P = 0.004) in UBR in animals with severe pneumonitis (0.44 ± 0.05) when compared with controls (0.24 ± 0.03). This impairment in lung clearance correlated with the increase in lung weight and the decrease in plasma ACE levels. Mice with kerosene pneumonitis had zones of lung injury, and areas with no gross signs of tissue damage. Lung clearance of S. aureus was significantly impaired in damaged areas whereas it was no different from controls in the non-affected areas. It is suggested that the measurement of plasma ACE activity may be an adjunct in the assessment of the extent of lung injury in hydrocarbon aspiration in children.
The Role of Intentional Self Regulation, Lower Neighborhood Ecological Assets, and Activity Involvement in Youth Developmental Outcomes.

Extracurricular activities provide a key context for youth development, and participation has been linked with positive developmental outcomes. Using data from the 4-H Study of Positive Youth Development (PYD), this study explored how the intentional self regulation ability of youth interacted with participation in extracurricular activities to affect PYD among adolescents living in neighborhoods with relatively low ecological assets. In total, 545 youth were included in the study (50.3% female). Most of the youth were European American (41%) or Latino (37%; African American, 10%; Asian American, 7%; Native American, 4%; and other, 1%). In general, youth with the greatest capacity to self regulate benefitted the most, as compared to their peers with less capacity to self regulate, from involvement in extracurricular activities. Consistent with a developmental systems perspective, and specifically with bioecological theory, the findings from this study confirmed that, within lower asset settings, children with the most positive person-level factors (intentional self regulation) benefit the most from proximal processes such as extracurricular activity involvement.
A double-blind evaluation of transfer factor therapy of HBsAg-positive chronic aggressive hepatitis: Preliminary report of efficacy☆

Abstract A controlled, prospective, double-blind trial of transfer factor in chronic aggressive hepatitis was carried out. This report presents the results obtained from study of the nine HB s Ag-positive subjects who were included in the trial. Transfer factor was prepared from adults who had recovered from acute hepatitis B or from acute non-B viral hepatitis and was administered to five HB s Ag-positive subjects. Four HB s Ag-seropositive subjects received placebo. Percutaneous liver biopsy was performed at the beginning and at the conclusion of the 10-week study period; biochemical and clinical parameters were monitored throughout. Cell-mediated immunity was assessed at the beginning and at the end of the study period. Four of five transfer factor recipients showed moderate or marked improvement in hepatic histology, clinical status, and serum transaminase levels, while none of four placebo recipients demonstrated improvement. The difference in response between the two groups was significant ( P = 0.048). No consistent changes in in vivo or in vitro correlates of cell-mediated immunity were demonstrated. No adverse effects were noted among transfer factor recipients. These data suggest that transfer factor may be of benefit in chronic aggressive hepatitis associated with HB s Ag. Additional studies appear to be indicated to delineate the mode of action of transfer factor as well as the role that such immunotherapy should play in the management of patients with this disorder.
The effects of aestivation on the catalytic and regulatory properties of pyruvate kinase from Helix aspersa

Abstract 1. 1. Pyruvate kinase was partially purified from the foot, mantle, and digestive gland of active and aestivating snails. 2. 2. At pH 7.0 the apparent K m values for phosphoenolpyruvate (PEP) were 0.064 mmol/l for the enzyme from foot and 0.071 mmol/l for the enzyme from mantle; those for ADP were 0.35 mmol/l for the foot enzyme and 0.33 mmol/l for the mantle enzyme. 3. 3. Both enzymes were inhibited by alanine, and this could be reversed by fructose 1,6-bisphosphate (FBP), although FBP alone was a weak activator. 4. 4. Decreasing the pH to 6.5 markedly increased the inhibition by alanine and reduced the response to FBP. 5. 5. The enzymes from these tissues of aestivating snails showed a small decrease in their affinity for PEP and a small increase in the effectiveness of alanine as an inhibitor. 6. 6. These changes are indicative of a down-regulation of this enzyme which is consistent with the observations in other species during metabolic depression. 7. 7. In contrast the enzyme from the digestive gland of active animals showed sigmoidal saturation kinetics for PEP with a S 0.5 of 1.2 mmol/l, but had a markedly higher affinity for PEP, S 0.5 = 0.20 mmol/l during aestivation. This may be indicative of other metabolic changes occurring in the digestive gland.
The Relationship among Wellness, Psychological Distress, and Social Desirability of Entering Master's-Level Counselor Trainees

Two-hundred and four entering master's-level counseling students from 9 programs in 5 states participated in a study testing the only counseling-based wellness assessment measure, the Five Factor Wellness Evaluation of Lifestyle (J. E. Myers, R. M. Luecht, & T. J. Sweeney, 2004), for its relationship to 2 other constructs: psychological distress and social desirability. There was a statistically significant negative relationship between level of wellness and psychological distress; the relationship between level of wellness and social desirability was found to have no statistical significance; and there was a statistically significant negative relationship between level of social desirability and psychological distress. Implications for counselor education and clinical significance are included.
Conservative surgical therapy for penile and urethral carcinoma

Abstract Objectives. Invasive penile and urethral tumors are traditionally treated with aggressive excision that requires involved organ and adjacent organ sacrifice. An alternative approach seeks to completely excise the tumor with adequate margins while preserving form and function of the organ. We present 6 patients who underwent such organ-sparing surgery. Methods. Six selected cases (4 penile and 2 urethral) are presented with operative photographs and pertinent data. Results. Three distal tumors of the penis were treated with excision limited to the glans with histopathologic findings of verrucous carcinoma, melanoma, and angiosarcoma. One patient with squamous cell carcinoma of the distal shaft refused partial penectomy and underwent a local wedge resection. A patient with locally advanced bulbourethral transitional cell carcinoma (TCC) refused cystourethrectomy and underwent an anterior urethrectomy and perineal urethrostomy. A 48-year-old woman with an adenocarcinoma contained in a very distal urethral diverticulum underwent simple diverticulectomy and excision of distal urethra. Postoperative voiding and sexual function were well preserved. Follow-up was 12 to 48 months. The patient with angiosarcoma died of lung metastases at 48 months with no local disease, and the patient with bulbourethral TCC developed pelvic disease at 12 months with no local recurrence and died of metastases at 25 months. Conclusions. Organ-sparing surgery is appropriate in selected patients on the basis of stage and location, high risk of distant failure, and patient disposition. Close follow-up is necessary. Comanagement with reconstructive and oncologic specialists optimizes results and outcomes.
Least squares algorithms for finding solutions of overdetermined linear equations which minimize error in an abstract norm

In this paper overdetermined linear equations inn unknowns are considered. Ifm is the number of equations, let ? m be equipped with a smooth strictly convex norm, ?·?. Algorithms for finding "best-fit" solutions of the system which minimize the ?·?-error are given. The algorithms are iterative and in particular apply to the important case where ? m is given thel p -norms, (1<p<?). The algorithms consist of obtaining a least square solution i.e. carrying out an orthogonal projection at each stage of the iteration and solving a non-linear equation in a single real variable. The convergence of the algorithms are proved in the paper.
Role of Insulin in Growth Hormone-Stimulated 3T3 Cell Adipogenesis*

The role of insulin during GH-stimulated adipogenesis of 3T3-F442A fibroblasts was investigated. Adipogenesis in defined medium (DM), as quantified by the level of glycerol-3-phosphate dehydrogenase activity, revealed that there existed a strict requirement for both insulin and GH during adipogenesis. The concentration of insulin required to elicit halfmaximal adipogenesis was approximately 20 nM. Insulin-like growth factor I was less effective than insulin in promoting adipogenesis, indicating that insulin action during differentiation was most likely mediated through the insulin receptor. Cellular viability was not compromised by the absence of insulin, as judged by colony-forming efficiency or trypan blue exclusion. Deletion of insulin from DM supplemented with 1 nM recombinant human GH reduced glycerol-3-phosphate dehydrogenase activity to uninduced levels. Removal of other individual DM constituents did not have this effect. The growth factors fibroblast growth factor, platelet-derived growth factor,...
On a Likelihood Approach for Monte Carlo Integration

The use of estimating equations has been a common approach for constructing Monte Carlo estimators. Recently, Kong et al. proposed a formulation of Monte Carlo integration as a statistical model, making explicit what information is ignored and what is retained about the baseline measure. From simulated data, the baseline measure is estimated by maximum likelihood, and then integrals of interest are estimated by substituting the estimated measure. For two different situations in which independent observations are simulated from multiple distributions, we show that this likelihood approach achieves the lowest asymptotic variance possible by using estimating equations. In the first situation, the normalizing constants of the design distributions are estimated, and Meng and Wong's bridge sampling estimating equation is considered. In the second situation, the values of the normalizing constants are known, thereby imposing linear constraints on the baseline measure. Estimating equations including Hesterberg's ...
Microorganisms associated with epithelial surfaces and stability of the indigenous gastrointestinal microflora

Indigenous microorganisms of many genera and species associate with mucosal epithelia in the gastrointestinal tracts of animals and humans. These mechanisms may involve a high degree of specificity for host and surface habitat. They may include a capacity of the microorganisms to adhere to the membranes of substratum epithelial cells, to colonize and utilize as a source of nutrients the mucus overlying epithelial cells, and to be motile and attracted into the mucous layer by chemotaxis. The microbes must be able as well to thrive in the nutritional and environmental conditions prevailing on the epithelial surfaces. Microbial communities associated with epithelial surfaces are critical for maintaining a microflora in areas of the tract (i.e., stomach, small intestine) where the lumenal content moves at a rate exceeding the maximum rates at which indigenous microorganisms can multiply. Such communities even may be important in areas (i.e., the cecum and colon) where the content moves at rates below those at which the microbes can multiply. In such areas, microorganisms colonizing mucus on the epithelium and in the crypts of Lieberkuhn may provide a stable inoculum for the lumenal content which may be altered in composition in times of dietary change. Microorganisms associated with gastric and intestinal surfaces undoubtedly serve in a major way to stabilize the composition of the indigenous gastrointestinal microflora. At the molecular level, however, little is known about the mechanisms stabilizing the composition or the biochemical and genetic activities of the microflora. Such mechanisms are important subjects for research in the future.
GE-19GENOMICS GUIDED THERAPEUTIC APPROACH FOR THE TREATMENT OF GLIOBLASTOMA MULTIFORME (GBM) USING NEXT GENERATION SEQUENCING (NGS) TECHNOLOGIES

BACKGROUND: The genomic heterogeneity of glioblastoma likely underlies the low response rates (8-24%) for targeted agents among unselected populations. We tested whether NGS would be useful in identifying therapeutically-actionable genetic alterations; we sought to test if this translated into improved tumor control in a patient-derived GBM model. METHODS: Tumor specimens from each patient (n = 11) that were used for analyte extraction contained between 70-80% viable tumor cellularity. Genome sequence coverage was more than 30X for both tumor and germline genomes; tumor RNA sequencing included over 100 million reads. NGS of paired tumor and germline DNA enabled detection of single nucleotide variations (SNVs), indels, translocations, intra-chromosomal rearrangements, and copy number alterations. A custom drug-matching workflow utilizing publically available databases and curated literature on reported drug effects, pharmacokinetics, and blood-brain barrier (BBB) penetration was used to map individual gene alterations in tumors with associated drug-response relationships. One specimen was tested in vitro and in vivo using a matched, patient-derived xenograft model. RESULTS: NGS for the 11 tumor panel found ~30% of cases with EGFR amplification, p16, and/or PTEN deletion. Novel potentially actionable targets included a TRIM54-FGFR3 fusion, STAG2 mutation, KIF11 and KIF15 mutation, and BRAF amplification. One recurrent, MGMT-unmethylated GBM line with a TRIM54-FGFR3 fusion underwent chemovulnerability testing. Cyquant proliferation assays demonstrated sensitivity to the pan-FGFR1-3 inhibitor AZD4547 when compared to a line without FGFR alteration (IC50 3uM vs >10uM). Furthermore, a flank PDX study demonstrated significant activity by AZD4547 when compared with either placebo or temozolomide, resulting in near complete tumor stasis at 82+ days of dosing with AZD4547. CONCLUSIONS: These results support the notion that therapeutic planning for treatment of GBM can be individualized and predicted by genome- and transcription-based analysis on the primary tumor, with the ultimate goal to design individualized GBM therapy based upon genetic markers for treatment sensitivity.
Drinking Patterns of Older Adults with Chronic Medical Conditions

BACKGROUND Understanding alcohol consumption patterns of older adults with chronic illness is important given the aging baby boomer generation, the increase in prevalence of chronic conditions and associated medication use, and the potential consequences of excessive drinking in this population.
Model selection using modified AIC and BIC in joint modeling of paired functional data

A modified version of the Akaike information criterion and two modified versions of the Bayesian information criterion are proposed to select the number of principal components and to choose the penalty parameters of penalized splines in a joint model of paired functional data. Numerical results show that, compared with an existing procedure using the cross-validation, the procedure based on the information criteria is computationally much faster while giving a similar performance.
School-based primary prevention: What is an effective program?

Our model makes us pessimistic about quick-fixes. Short-term, narrowly focused programs designed to increase children's knowledge or some limited aspect of their competence are unlikely to be effective in preventing AIDS. Our model suggests that what protects a child from AIDS is not knowledge or isolated social skills but rather the quality of bonds to school, family, and other socialization agents. Ultimately, the school-based route to prevention of AIDS will work only if schools are effective socialization agents: effective in meeting children's needs for autonomy, belonging, and competence, and thereby in helping children build the motivation and social competence they will need to avoid many kinds of high-risk behavior over many years.
The Influence of Five Alternative Myosin Converter Domains on Drosophila Muscle Mechanical Properties

In Drosophila, alternatively spliced myosin isoforms containing five different converter sequences (11A-11E) are expressed in a diverse range of muscle types including the superfast indirect flight muscle (IFM), jump muscle and slow embryonic muscles. We measured the converter's influence on IFM fiber mechanical properties such as maximum power output (Pmax), frequency of maximum power output (Fmax), strain for maximum power output (AMP), stretch activated tension (Fsa) and mechanical rate constants 2pib and 2pic. Using the work loop technique to impose muscle strain amplitudes that simulate in vivo conditions, we found that transgenically replacing the IFM-11A converter with the embryonic-11D version significantly reduced Pmax by 41%, decreased Fmax by 63%, and increased AMP by 100%. However, no change in Fsa was detected for the IFM fibers expressing the 11D converter. Preliminary results from transgenic substitution of the IFM-11A converter with the embryonic-11E version showed a 50% reduction in Pmax and a 57% reduction in Fmax compared to control muscle fibers. The mechanical rate constant 2pib, determined by sinusoidal analysis, was reduced by 55% by substituting the 11D converter and by 68% by substituting the 11E converter into the IFM myosin isoform. The mechanical rate constant 2pic, increased by more than 50% after substitution of 11D and about 100% with the 11E converter switched into the IFM myosin isoform. These results are physiologically significant as we observed decreased wing beat frequencies of 11% for the 11D, 15% for 11E and decreased flight performance for the 11D fly line at 15°C. We conclude that the five converter versions provide for a wide variation in muscle mechanical properties between muscle fiber types.
A review of the Torodora recurvata species group in the Philippines, with descriptions of ten new species (Lepidoptera, Lecithoceridae)

As part of studies of the genus Torodora Meyrick (Gelechioidea, Lecithoceridae, Torodorinae) in the Philippines, the Torodora recurvata species group is newly proposed, with 14 identified species, ten of which are new species described herein: T. candida sp. nov., T. argenteola sp. nov., T. parvifoliae sp. nov., T. pediformis sp. nov., T. chatolensis sp. nov., T. lechridia sp. nov., T. cavecostalis sp. nov., T. meyi sp. nov., T. pinigisanica sp. nov. and T. castanea sp. nov. A full bibliography and diagnosis for all known species and descriptions of the new species are provided, together with illustrations of the male or female genitalia. A key to the species of the group based on the external characteristics is also provided. Seven species originally assigned to the genus Lecithocera Herrich-Schaffer are transferred to the genus Torodora Meyrick: T. activata (Diakonoff), comb. nov., T. ochrocapna (Meyrick), comb. nov., T. recurvata (Meyrick), comb. nov., T. niphotricha (Diakonoff), comb. nov., T. argocrossa (Meyrick) comb. nov., T. claustrata (Meyrick), comb. nov., T. orbata (Meyrick), comb. nov. Lecithocera phanerostoma Diakonoff is synonymized with T. recurvata (Meyrick), syn. nov. One previously reported species, T. ochrocapna (Meyrick) was not found in this study.
Bulk and surface correlations in a microemulsion.

Small angle neutron scattering and neutron reflectivity are used to study the bulk and surface structure of water--octane--tetraethylene glycol monodecyl ether (C{sub 10}E{sub 4}) bicontinuous microemulsions. When the hydrophilicity and hydrophobicity of the surfactant monolayers in the microemulsion are balanced, the surface correlation length is found to be significantly larger than its bulk analog. Varying the spontaneous curvature of the monolayers greatly influences the surface structure of the microemulsion while having a relatively slight effect on the bulk correlation function. These observations are explained using a Ginzburg-Landau theory.
Floor control for large-scale MBone seminars

The development of MBone videoconferencing tools has led to a large number of seminars being broadcast over the internet. Most MBone seminars have little remote participation. One reason might be the absence of good floor control mechanisms. This paper describes a tool we developed, called the Questionboard, that implements floor control to facilitate question asking in large-scale MBone seminars. The qb protocol is described including the mechanisms used for reliable transmission of data and the floor control and crash recovery protocols. (June 10, 1997)
Global crop exposure to critical high temperatures in the reproductive period: historical trends and future projections

Long-term warming trends across the globe have shifted the distribution of temperature variability, such that what was once classified as extreme heat relative to local mean conditions has become more common. This is also true for agricultural regions, where exposure to extreme heat, particularly during key growth phases such as the reproductive period, can severely damage crop production in ways that are not captured by most crop models. Here, we analyze exposure of crops to physiologically critical temperatures in the reproductive stage (Tcrit), across the global harvested areas of maize, rice, soybean and wheat. Trends for the 1980–2011 period show a relatively weak correspondence (r = 0.19) between mean growing season temperature and Tcrit exposure trends, emphasizing the importance of separate analyses for Tcrit. Increasing Tcrit exposure in the past few decades is apparent for wheat in Central and South Asia and South America, and for maize in many diverse locations across the globe. Maize had the highest percentage (15%) of global harvested area exposed to at least five reproductive days over Tcrit in the 2000s, although this value is somewhat sensitive to the exact temperature used for the threshold. While there was relatively little sustained exposure to reproductive days over Tcrit for the other crops in the past few decades, all show increases with future warming. Using projections from climate models we estimate that by the 2030s, 31, 16, and 11% respectively of maize, rice, and wheat global harvested area will be exposed to at least five reproductive days over Tcrit in a typical year, with soybean much less affected. Both maize and rice exhibit non-linear increases with time, with total area exposed for rice projected to grow from 8% in the 2000s to 27% by the 2050s, and maize from 15 to 44% over the same period. While faster development should lead to earlier flowering, which would reduce reproductive extreme heat exposure for wheat on a global basis, this would have little impact for the other crops. Therefore, regardless of the impact of other global change factors (such as increasing atmospheric CO2), reproductive extreme heat exposure will pose risks for global crop production without adaptive measures such as changes in sowing dates, crop and variety switching, expansion of irrigation, and agricultural expansion into cooler areas.
Who should profit from the business of science? Public money, private gain, profit for all.

What level of financial incentive is necessary in order to encourage the commercial applications of beneficial scientific findings? Some argue that the public and private economic worlds are inextricably intertwined and that all benefit when entrepreneurs seek to turn scientific knowledge into profit. Others believe that the unregulated acquisition of profits is unjustified if it clearly derives from public funds or the nonprofit research activities of others.