cssi/SciSciGPT-SciSciNet huggingface dataset:
Breast cancer ( BRCA ) gene testing in ovarian cancer

The discovery of cancer-causing BRCA1/2 mutations and the emergence of genetic testing have brought precision in patient selection for poly-(ADP)-ribose polymerase inhibitor (PARPi) treatment. Interestingly, patients who are carriers of BRCA1/2 mutations have a higher risk for developing cancer, but respond better to DNA-damaging cytotoxic therapy, such as platinum-based chemotherapy. The distinctive biology of ovarian cancer involves high genomic instability consisting of gene amplification, gene deletion, oncogene hypomethylation, loss of heterozygosity, and tumor suppressor gene promoter hypermethylation in many of the DNA damage response (DDR) genes, including BRCA1/2. Several of these genetic abnormalities can impair high fidelity DNA damage repair increasing the therapeutic audience for PARPi's. This is especially important given the clinical development over the last decade of this group of agents and the dramatic increase in progression free survival among ovarian cancer patients who received PARPi, both in treatment or maintenance setting. In this review, we summarize our current understanding of the role of BRCA1/2 mutations in ovarian cancer and present relevant clinical trials in which BRCA1/2 was investigated as biomarker for therapy. We also outline the role of homologous recombination (HR) deficiency as biomarker by presenting the recent clinical development and recent approvals PARPi for firstline maintenance in ovarian cancer.
Trends in utilization of neoadjuvant and adjuvant chemotherapy for muscle invasive bladder cancer

PURPOSE Previous studies have noted increased utilization of perioperative chemotherapy over time. The goal of this study was to determine trends in perioperative chemotherapy use within a contemporary population. MATERIALS AND METHODS The National Cancer Database was queried for patients diagnosed with cT2-4N0M0 urothelial muscle invasive bladder cancer from 2011 to 2015 and underwent subsequent radical cystectomy. We retrospectively analyzed factors associated with perioperative chemotherapy and evaluated overall treatment trends in the use of neoadjuvant and adjuvant chemotherapy. Linear regression, logistic regression, Cox regression, and Kaplan-Meier analysis were performed. RESULTS In total, 7,101 patients met inclusion criteria for analysis. The use of perioperative chemotherapy increased from 46.4% in 2011 to 57.2% in 2015 (p=0.003). Neoadjuvant chemotherapy use increased from 22.9% to 32.3% (p=0.007) over the time period analyzed, while adjuvant chemotherapy use experienced no significant change (23.5% to 24.9%, p=0.182). Logistic regression demonstrated that increased age and Charlson Comorbidity Index were predictors of not receiving chemotherapy (p<0.05), while those with increasing T stage, income above $48,000, and insurance other than Medicaid or Medicare were more likely to receive perioperative chemotherapy (p<0.05). Kaplan-Meier analysis revealed patients receiving neoadjuvant chemotherapy had the best 5-year overall survival at 48.3% compared to adjuvant chemotherapy (42.6%) or no chemotherapy (37.8%) (p<0.001). CONCLUSIONS The increasing use of perioperative chemotherapy noted in prior studies has continued through 2015. Neoadjuvant chemotherapy appears to drive this increase while adjuvant chemotherapy utilization remains unchanged. Clinical and socioeconomic factors affect utilization of perioperative chemotherapy.
“We Know What They’re Going Through”: Social Support from Similar versus Significant Others

Stress research overlooks the possible importance of similar-other support – assistance from people experienced with an individual’s stressor. Theoretically, similar-other support should provide di...
Single-cell immune repertoire tracing identifies rituximab refractory B cells that emerge during relapse

Abstract Rituximab, an anti-CD20 B cell-depleting therapy, is indicated to treat a growing number of autoimmune disorders. However, disease relapses can occur when the B cell compartment is re-established after treatment. To explore the mechanism of relapse, we studied patients with muscle-specific kinase (MuSK) myasthenia gravis (MG), a paradigm for B cell-mediated autoimmune diseases in which pathology is directly associated with autoantibody production. Whether the failed depletion of specific clones leads to the persistence of autoantibody producing B cell subsets has yet to be elucidated. Here we show that rituximab (RTX) therapy is not fully effective at eliminating disease-associated B cells and provide a mechanistic understanding of relapse. We carried out single-cell transcriptional and B cell receptor (BCR) profiling on longitudinal B cell samples from the peripheral blood of MuSK MG patients who relapsed after rituximab therapy. Computational analysis of these data identified individual B cells that were refractory to rituximab depletion by linking them to clones that were present prior to therapy and continued to persist after therapy. These persistent B cell clones were present at high frequency, and included both antibody-secreting cells and memory B cells. They were disproportionately isotype switched with elevated somatic hypermutation frequencies and a gene expression signature associated with antigen-experience and B cell clonal expansion. We further identified both antibody-secreting cells and memory B cells with specificity for MuSK autoantigen that were clonally expanded during relapse and persistent. Our results provide evidence that post-rituximab relapse in MuSK MG is associated with the failed depletion of autoantigen-specific B cell subsets. This work provides insight into the durability of human B cells during treatment with therapeutic CD20-specific monoclonal antibodies. The transcriptional signatures associated with B cell resistance may represent new therapeutic avenues for treatment and biomarkers of depletion efficacy.
Techniques to Thwart Surreptitiously Altered PCBs

Printed circuit boards (PCBs, also known as Printed Wiring Boards or PWBs) are in nearly ubiquitous use in electronic and computer systems. While often regarded as mundane, PCBs provide vital interconnection capabilities. Incorrect PCB design causes systems to fail. Cybersecurity efforts have been justifiably focused on integrated circuits due to the possibility of malicious alteration, but little or no attention has been paid to the PCB. Conversely, malicious alteration of PCBs is extremely simple. After reviewing work on the ways that PCBs can be altered, this presents a taxonomy of circuit-board attacks and techniques for detecting alterations.
Nature’s forms are frilly, flexible, and functional

A ubiquitous motif in nature is the self-similar hierarchical buckling of a thin lamina near its margins. This is seen in leaves, flowers, fungi, corals, and marine invertebrates. We investigate this morphology from the perspective of non-Euclidean plate theory. We identify a novel type of defect, a branch-point of the normal map, that allows for the generation of such complex wrinkling patterns in thin elastic hyperbolic surfaces, even in the absence of stretching. We argue that branch points are the natural defects in hyperbolic sheets, they carry a topological charge which gives them a degree of robustness, and they can influence the overall morphology of a hyperbolic surface without concentrating elastic energy. We develop a theory for branch points and investigate their role in determining the mechanical response of hyperbolic sheets to weak external forces.
Burden of Disease in Patients with Refractory Myasthenia Gravis (P5.4-037)

Objective: To explore the demographics, disease characteristics and burden in refractory myasthenia gravis (MG). Background: Approximately 10–15% of patients have difficult to control disease and are termed as ‘refractory’. The purpose of our study was to further evaluate clinical characteristics, disease burden and financial impact on this population. Design/Methods: This study was a retrospective medical record review of patients with confirmed MG that had been included in the Exploring Outcomes and Characteristics of Myasthenia Gravis (EXPLORE-MG) Registry and followed at the Yale MG Clinic from 2003 to 2018. Information collected include demographics, antibody status, disease phenotype, worst/last MGFA clinical class, thymoma/thymectomy status, history of autoimmunity, age at diagnosis, therapy utilized, hospitalizations, and financial impact of disease. Pre-specified criteria were used to classify the refractory and non-refractory groups. Results: Sixty-two (21%) out of 297 patients were classified as refractory, and further characterized as predominantly women (64.5%) with early-onset generalized MG (p-value Conclusions: Patients with refractory MG have key clinical characteristic differences including a greater burden of disease. Understanding disease burden from both a quality of life and financial perspective as well as further characterizing it remains a high priority as treatment paradigms emerge for patients with difficult to manage MG. Disclosure: Dr. Sharma has nothing to disclose. Dr. Roy has nothing to disclose. Dr. Khokhar has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with BioHaven Pharmaceuticals. Dr. Nowak has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alexion Pharmaceuticals, Ra Pharma, Momenta, and Roivant. Dr. Nowak has received research support from Alexion Pharmaceuticals, Ra Pharma, and Grifols.
A Finite Difference Scheme for Pairs Trading with Transaction Costs

We consider a pairs trading stochastic control problem with transaction costs and constraints on the gross market exposure, and propose a new monotone Finite Difference scheme approximating the viscosity solution of the Hamilton–Jacobi–Bellman equation characterizing the optimal trading strategies. Given a fixed time horizon and a portfolio of two cointegrated assets, the agent trades the spread between the two assets and the trading strategy is defined as the possibly negative portfolio weight maximizing the expected exponential utility derived from terminal wealth. Furthermore, trades incur transaction costs comprised of explicit transactions fees and commissions and the implicit cost due to slippage. These costs are modeled as a linear or square root function of the trading rate and respectively added or subtracted from the observable asset price at the time when a buy or a sell order enters the market. Our main contribution is the derivation of a robust approximation for the nonlinear transaction cost term in the Hamilton–Jacobi–Bellman equation. Finally, we combine our monotone Finite Difference scheme with a Monte Carlo sampling method to analyze the effects of transaction fees and slippage on the trading policies’ performance.
Transpersonal Psychology Promise and Prospects

This survey of transpersonal psychology focuses on three major domains—the psychology of personal development, the psychology of consciousness, and spiritual psychology. These three main areas overlap to form the field of transpersonal psychology.
Oxidative Stress in Chronic Viral Hepatitis

Chronic viral hepatitis (CVH), a state of persistent infection marked by inflammation, is a global health concern with more than half a billion people chronically infected with hepatitis C virus (HCV) and/or hepatitis B virus (HBV). The mechanism by which CVH induces liver disease, including fibrosis, cirrhosis, and hepatocellular carcinoma (HCC), involves oxidative stress. Oxidative stress has been extensively observed in CVH, particularly in chronic hepatitis C (CHC). Mechanisms of oxidative stress in CHC include hepatic iron overload, elevated mitochondrial reactive oxygen species (ROS) generation, upregulation of NADPH oxidase (Nox) enzymes in hepatocytes and host immune cells, and decreases in the host antioxidant defense. Oxidative stress has also been reported in chronic hepatitis B (CHB). Progression to HCC is marked by accumulation of oxidative DNA damage and several redox-regulated processes including tumor necrosis factor α (TNF-α), hypoxia-inducible factor 1 (HIF-1), and activation of toll-like receptor 4 (TLR4) signaling. Evidence suggests that hepatic fibrosis, mediated by transforming growth factor β (TGF-β), and extrahepatic manifestations of CHC, which include type 2 diabetes mellitus (T2DM), may also be mediated by oxidative stress. Further studies, however, will be needed to determine whether strategies that target oxidative stress would be beneficial in the treatment of CVH.
Rheumatoid arthritis: Guidelines for RA therapy-avoiding hamartia.

Treatment guidelines are an increasingly prominent topic of discussion in medicine. Can rheumatologists avoid the 'fatal flaw' inherent in attempts to standardize treatment decision-making—in which overly strict adherence to guidelines might be pursued at the expense of optimizing individual patients' outcomes?
Ultrasonic imaging using trapped energy mode Fresnel lens transducers

A focusing transducer utilizing trapped energy modes can be easily fabricated by plating a number of concentric rings of electrodes on a suitable piezoelectric plate of uniform thickness. The concentric ring structure acts as a Fresnel lens and can be used to obtain excellent lateral focusing of ultrasonic waves. Several transducers operating in the 2–5 MHz range have been produced using PZT-7A as the piezoelectric material. The near field radiation pattern has been observed directly in front of the plate using the first order diffraction peak from a laser probe. It is confirmed that there is good acoustic isolation between the rings and that they radiate in the trapped energy mode. The ultrasonic radiation pattern of the Fresnel lens has been observed at various distances from the plate and compared with computed results which show excellent agreement. Furthermore, the axial diffraction pattern of the lens can be optimized by adjusting ring spacings. During the course of this study a new, previously unreported mode of energy trapping has been discovered. The explanation for this method of trapping is briefly discussed. Finally an acoustic through-transmission imaging system incorporating one focusing transducer is used for imaging of flaws in composite materials.
Determination of volume and water permeability of plated cells from measurements of light scattering

Measurements of cell membrane water osmotic permeabilities can be inaccurate because of the technical difficulties inherent to cell volume measurements and because of the presence of an unstirred water layer in contact with the cells. We detail here a method we have developed to quantify transient changes in cell volumes from the intensity of light scattered by cells. For this, we theorize how an unstirred layer originates in a perfusing chamber, and we calculate values for both cell membrane water osmotic permeability and unstirred layer thickness from time transient changes in scattered light. We apply a computer algorithm that finds the best correspondence between experimental data and estimated values. This is done by solving a differential equation governing cell volume changes by numerical integration (Runge-Kutta) and iterating the procedure varying the test values of osmotic permeability and unstirred layer thickness until the best fit is achieved. We exemplify this procedure with experimental results obtained in adherent cultured cells.
Diversity of T cell receptor-alpha chain transcripts from hyperimmune alloreactive T cells.

Alloreactive T cells represent a relatively large fraction of the T cell population compared with the fraction of T cells that are specific for other foreign Ag. Recent findings indicate that most alloreactive T cells recognize endogenous peptides in association with a non-self MHC product. In light of these observations, it is perhaps not surprising that previous studies of the size of the TCR-alpha beta repertoire among alloreactive cells showed that they express many different V alpha and V beta genes. To further access the extent of diversity among alloreactive cells, we examined V alpha J alpha combinatorial diversity in polyclonal populations of a BALB/c anti-BALB.B mixed lymphocyte response. A long term culture from naive mice contained a diverse repertoire of V alpha J alpha combinations that was similar to the diversity present among unstimulated splenic T cells. In contrast, long term cultures from hyperimmunized animals contained "dominant" clones of T cells that expressed a restricted repertoire of V alpha J alpha combinations. Examination of the nucleotide sequences of these alpha-chains suggested that there was selective expansion of T cells with identical alpha-chains. In addition, T cells that express the same V alpha J alpha combination but different junctions were also identified. Consistent with previous results, the isolates from hyperimmune animals did not contain somatic mutations in the CDR3 region of the alpha-chains. Nevertheless, the results suggest that T cells may be subject to in vivo selection and clonal expansion analogous to the process of affinity maturation of Ig.
A high-efficiency Monte Carlo receiver for digital communications

Stochastic Bayesian detection has recently emerged as a competitive receiver design paradigm for wireless communications applications. It uses Monte Carlo simulations to perform Bayesian inference of a probabilistically modeled communication system so as to obtain the maximum a posterior (MAP) symbol detection and/or channel estimation results. The Monte Carlo concept is attractive in that it is intuitive, optimal, and works for generic Bayesian network structures. However, conventional Monte Carlo methods suffer from poor convergence especially when there is less likely evidence in the collected samples, in which case the simulations are wasted in sample spaces that contribute little to the inference estimates. We present an adaptive sampling method in which the sample allocation process is optimized for efficient MAP detection. It is then demonstrated that this optimized adaptive sampling method can be applied to wireless communication systems for high-efficiency symbol detection and channel estimation. The effectiveness of the derived blind Bayesian multiuser detection is verified by computer simulations.
2004 Dr. Gary J. Becker Young Investigator Award: Relative thermosensitivity of cytotoxic drugs used in transcatheter arterial chemoembolization

PURPOSE Large hepatocellular carcinoma tumors are being treated increasingly with a combination of transcatheter arterial chemoembolization (TACE) and radiofrequency (RF) ablation. However, the high temperatures reached during RF ablation may reduce the cytotoxic effects of antineoplastic agents, but this has not been studied. Therefore, in the present study, the relative thermosensitivity of cytotoxic drugs commonly used in TACE was studied. MATERIALS AND METHODS The relative cytotoxic effects of cisplatin, doxorubicin HCl, and mitomycin on the growth of human colon HT29 and lung A549 adenocarcinoma cells before and after heating each drug in solution was determined from the standpoints of different durations of exposure (15, 30, 60, 90, and 120 minutes) at a fixed temperature (120°C) and exposure to different temperatures (60°C, 80°C, 100°C, and 120°C) for a fixed period of time (2 hours). After 72 hours of exposure of the cells to each drug, relative cell growth inhibition was assessed by MTT assay, and 50% inhibitory concentration (IC 50 ) values were calculated for each cytotoxic agent. Finally, the heat-dependent degradation of mitomycin and doxorubicin was analyzed with use of tandem electrospray mass spectrometry. RESULTS The relative cytotoxic activities (shown by cell growth inhibition and IC 50 values) of cisplatin, doxorubicin, and mitomycin heated to 120°C for 2 hours decreased by factors of 1.35 (range, 1–1.75), 9.5 (range, 8.5–10.5), and 7.05 (range, 3.5–12), respectively. The cytotoxic activities of doxorubicin and mitomycin continued to decrease with incremental increases in temperature. Similarly, with incremental increases in the duration of exposure to heat, the cytotoxic activities of doxorubicin and mitomycin decreased. Mass spectrometric analysis of residual drug content showed that a 2-hour exposure to a temperature of 120°C caused doxorubicin and mitomycin to degrade by 95% and 84%, respectively. CONCLUSIONS The cytotoxicity of cisplatin is not affected by heat. The cytotoxicities of doxorubicin and mitomycin are reduced by high temperature and duration of exposure to heat. Although degradation of cytotoxicity starts at 60°C and after 30 minutes of exposure to heat, statistically significant changes are encountered at 100°C and after 90 minutes of exposure.
Relationship between Interviewers' and Applicants' Reciprocal Evaluations

The relationship between and among interviewers' evaluations of applicants and applicants' evaluations of interviewers in a college placement center was examined. 62 applicants being interviewed by 11 different recruiters from various industrial and academic agencies participated. Interviewers and applicants evaluated each other on three analogous dimensions: over-all general impression of the applicant (interviewer), personal liking of the applicant (interviewer), and chances that the applicant will receive further consideration by the organization (chances that the applicant would accept a job if offered). Intercorrelations between the interviewers' and the applicants' evaluations ranged from .12 to .42. Further, the interrelationships among the evaluations differed between the interviewers and the applicants. The evaluations of chances of further consideration (or offer acceptance) were more highly related to the other more interpersonal evaluations for the interviewers than for the applicants.
Hydroxyl radical formation via iron-mediated Fenton chemistry is inhibited by methylated catechols

The differing effects of O-methylated catecholamines and their dihydroxyphenyl precursors on the production of *OH were quantified using a previously established specific salicylate hydroxylation assay in conjunction with a sensitive electrochemical detection system. The production of *OH by the Fenton reaction was diminished significantly by O-methylated catecholamines (O-methyldopa, O-methyldopamine, O-methyltyrosine, and N-acetyl-O-methyldopamine), whereas radical production was augmented by dihydroxyphenyls (DOPA, dopamine, and N-acetyldopamine), including those with methylated side chains (N-methyldopamine and alpha-methyldopa). Monohydroxyphenyls such as octopamine, tyramine, tyrosine, and alpha-methyltyrosine had little or no effect on radical production. These data show that a methyl group positioned on the side chain of a catecholamine does not alter its pro-oxidant behavior, while a methyl group positioned on the aromatic ring renders the catecholamine sterically or kinetically unfavorable for coordination with transition metals, thus preventing the promotion of Fenton chemistry. These results highlight the importance of O-methylation in forming catechols that are less reactive than their dihydroxyphenyl precursors. Thus, factors regulating the methylation of brain catecholamines may play a crucial role in mediating neuronal integrity during aging and in the pathogenesis of certain neurodegenerative disorders. Competitive side-chain methylation reactions may sustain or perpetuate some dihydroxyphenyls, creating an oxidatively less favorable environment for cells than would result from compounds formed by O-methylation.
THE CONSISTENTLY INCONSISTENT APPLICATION OF CONTEMPT POWER IN JUVENILE COURTS

ABSTRACT A controversy exists over the legal authority of juvenile court judges to apply contempt power to incarcerate nondeliquent youths. The decisions by reviewing courts reflect three distinct approaches to contempt power. One approach gives juvenile court judges unlimited legal authority to incarcerate status offenders for disobeying court orders. A second holds incarceration for contempt to be inappropriate and contrary to legislative directives under each state's Juvenile Court Act. A third strikes a “middle-ground,” in which incarceration of nondeliquent youths for contempt is permissible within narrow legal parameters. Resolving the conflicts created by these disparate approaches likely will require federal court intervention.
Methane, Carbon Dioxide, and Nitrous Oxide Emissions from Septic Tank Systems

Emissions of CH4, CO2, and N2O from conventional septic tank systems are known to occur, but there is a dearth of information as to the extent. Mass emission rates of CH4, CO2, and N2O, as measured with a modified flux chamber approach in eight septic tank systems, were determined to be 11, 33.3, and 0.005 g capita(-1) day(-1), respectively, in this research. Existing greenhouse gas (GHG) emission models based on BOD (biochemical oxygen demand) loading have estimated methane emissions to be as high as 27.1 g CH4 capita(-1) day(-1), more than twice the value measured in our study, and concluded that septic tanks are potentially significant sources of GHGs due to the large number of systems currently in use. Based on the measured CH4 emission value, a revised CH4 conversion factor of 0.22 (compared to 0.5) for use in the emissions models is suggested. Emission rates of CH4, CO2, and N2O were also determined from measurements of gas concentrations and flow rates in the septic vent system and were found to be 10.7, 335, and 0.2 g capita(-1)day(-1), respectively. The excellent agreement in the CH4 emission rates between the flux chamber and the vent values indicates the dominant CH4 source is the septic tank.
Association of ferritin and lipids with C-reactive protein

Abstract C-reactive protein (CRP) and lipids (e.g., low-density lipoprotein [LDL]) are both markers of cardiovascular disease risk, yet they are not highly correlated. Oxidative stress of lipids induced by iron may play a role in vascular inflammation, as indicated by CRP. The purpose of this study was to examine, in a representative sample of United States adults, the relation between ferritin, lipids, and CRP. We analyzed data on adults (aged ≥25 years) in the National Health and Nutrition Examination Survey III, a national public-use data set collected between 1988 and 1994. Ferritin, total cholesterol, LDL, high-density lipoprotein, and ferritin-lipid combinations were analyzed in relation to CRP in age-, gender-, and race-adjusted models as well as models with other potential confounding variables. In adjusted models, neither elevated ferritin (odds ratio [OR] 1.11, 95% confidence interval [CI] 0.94 to 1.32) nor elevated LDL was significantly associated with elevated CRP (OR 1.03, 95% CI 0.79 to 1.33). Patients with elevated ferritin and elevated LDL were more likely to have elevated CRP (OR 1.68; 95% CI 1.06 to 2.68). Patients with elevated ferritin and low high-density lipoprotein were also more likely to have elevated CRP (OR 1.71; 95% CI 1.28 to 2.27). These results suggest that both iron and lipids induce inflammation. Future research needs to focus on preventive medicine to decrease iron in patients with elevated lipids.
Retrospective review of extra-pulmonary small cell carcinoma and prognostic factors

Extra-pulmonary small cell carcinoma (EPSCC) is a rare cause of malignancy, representing 2.5–5 % of all small cell carcinomas, with an incidence rate of 1000 cases per year in the USA. The purpose of this study is to characterize the location, extent of disease, and survival of patients with EPSCC, and to analyze potential clinical prognostic indicators predicting survival. A retrospective review of all patients with EPSCC between the years 2000 and 2010 was conducted. Patients included for analysis had pathologic diagnosis of EPSCC, poorly differentiated tumors, and negative chest imaging at diagnosis. 53 patients were included in the analysis. 23 patients (43 %) had limited disease (LD) at diagnosis, and 30 patients (57 %) had extensive disease (ED) at diagnosis. Carcinoma of unknown primary represented the largest proportion of patients (40 %), followed by genitourinary (26 %), gastrointestinal (15 %), head and neck (11 %), gynecologic (6 %), and breast (2 %). The median overall survival (OS) was 4.7 months; 14.5 months for LD, and 3.7 months for ED. Genitourinary EPSCC had the best median OS at 13.1 months, and GI carcinomas had the worst at 1.7 months. On univariate analysis, ED (p = 0.0001), non-genitourinary EPSCC (p = 0.036), and hyponatremia were associated with worse OS (p = 0.0176). In a cohort of patients with EPSCC, hyponatremia, non-genitourinary EPSCC, and extensive disease were associated with worse OS. Anatomic site predicted survival, which suggests that pathologic heterogeneity between individual tumor sites, including mixed tumor pathology, may affect the prognosis of this rare disease. Future directions for research should include thorough pathologic and genetic profiles.
Identification of vehicle components associated with severe thoracic injury in motor vehicle crashes: a CIREN and NASS analysis

Abstract Introduction Thoracic trauma secondary to motor vehicle crashes (MVC) continues to be a major cause of morbidity and mortality. Specific vehicle features may increase the risk of severe thoracic injury when striking the occupant. We sought to determine which vehicle contact points were associated with an increased risk of severe thoracic injury in MVC to focus subsequent design modifications necessary to reduce thoracic injury. Methods The National Automotive Sampling System (NASS) databases from 1993 to 2001 and the Crash Injury Research and Engineering Network (CIREN) databases from 1996 to 2004 were analyzed separately using univariate and multivariate logistic regression stratified by restraint use and crash direction. The risk of driver thoracic injury, defined as an abbreviated injury scale (AIS) of score ≥3, was determined as it related to specific points of contact between the vehicle and the driver. Results The incidence of severe chest injury in NASS and CIREN were 5.5% and 33%, respectively. The steering wheel, door panel, armrest, and seat were identified as contact points associated with an increased risk of severe chest injury. The door panel and arm rest were consistently a frequent cause of severe injury in both the NASS and CIREN data. Conclusions Several vehicle contact points, including the steering wheel, door panel, armrest and seat are associated with an increased risk of severe thoracic injury when striking the occupant. These elements need to be further investigated to determine which characteristics need to be manipulated in order to reduce thoracic trauma during a crash.
Acute excitotoxicity in chick retina caused by the unusual amino acids BOAA and BMAA: Effects of MK-801 and kynurenate

Abstract β-N- Oxalylamino- l -alanine (BOAA) and β-N- methylamino- l -alanine (BMAA) were tested for their ability to produce acute excitotoxicity in in embryonic chick retina. γ-Aminobutyric acid (GABA) release and histology were monitored in retina treated with various concentrations of BOAA, BMAA, kainate (KA), N- methyl- d -aspartate (NMDA), or glutamate. BOAA and BMAA caused retinal lesions similar to those produced by the excitatory amino acids. BOAA was slightly less potent than KA, whereas BMAA had a potency similar to glutamate. BOAA, like KA and NMDA, caused a dose-dependent increase in GABA release. Addition of the NMDA antagonist (+)-MK-801, completely blocked acute excitotoxicity caused by NMDA or BMAA but was ineffective against KA or BOAA. Kynurenate, a nonspecific glutamate receptor antagonist, and DIDS, a Cl − channel blocker, were effective in blocking all agonist-induced toxicity. It is concluded that BOAA and BMAA cause excitotoxic damage in retina; BOAA induces toxicity through a non-NMDA type glutamate receptor and BMAA through the NMDA receptor.
Stress-induced phase transformations insolids and the associated double-well potentials

Abstract The one-dimensional continuum modeling of phase transformations in solids presumesthe existence of a double-well Helmholtz free energy. The two well-bottoms are separated by a transformation strain e T and a transformation energy γ T . Both are in general temperature-dependent material properties. The determination of γ T , together with certain other thermodynamic properties, is by no means a trivial matter. A heat measurement, in conjunction with an energy identity, is proposed in this paper.
Boron carbides: Evidence for molecular level disorder

Abstract A Raman spectroscopic study confirms a structural model for boron carbides that was inferred from theory, transport data, and magnetic measurements. In this model substitutional disorder occurs within the icosahedra and chains that make up the boron carbide structure.
Synthesis and binding affinity of a fluorine-substituted peroxisome proliferator-activated gamma (PPARγ) ligand as a potential positron emission tomography (PET) imaging agent

The peroxisome proliferator-activated receptor γ (PPARγ) is an important regulator of lipid metabolism and the differentiation of pre-adipocytes. Thus, imaging PPARγ in vivo using positron-emission tomography (PET) might be useful in assessing lipid metabolism disorders and identifying tumor cell differentiation. A fluorine-substituted PPARγ ligand from tyrosine-benzophenone class, compound 1, has a very high affinity for PPARγ receptor (Ki = 0.14 nM). To develop this compound as a PPARγ PET imaging agent, we investigated synthetic routes suitable for its labeling with the short-lived PET radionuclide fluorine-18 (t1/2 = 110 min). To obtain the high specific activity material needed for receptor imaging with this isotope, reactions need to proceed efficiently, within a short time, starting from fluoride ion at the tracer level. The most promising approach involves introduction of fluorine into a suitable benzophenone precursor, followed by efficient coupling of this intermediate with the heterocyclic tyro...
Spin-bag theory of high-temperature superconductivity

Abstract Schrieffer et al have omitted most of the terms in the interaction and aspects of the transformation of the interaction to a basis of eigenfunctions in the spin-density-wave state. When this is corrected the pairing interaction is repulsive within the framework of their theory - there is no “spin-bag” theory for pairing of electrons at present.
Margin-based wrapper methods for gene identification using microarray

Abstract The gene expression data obtained from microarrays have shown useful in cancer classification problems. DNA microarray data have extremely high dimensionality compared with the small number of available samples. An important step in microarray studies is to select a small number of features (genes) for cancer classifications. In this paper, we propose a novel feature selection algorithm to identify a small set of genes from microarray data for cancer classification. This new wrapper method uses margins to evaluate subsets of genes; bootstrap methods are applied in genetic search to alleviate small sample size problems and support vector machines with maximum margins are used for classifications. The results of experiments carried out show that the proposed method successfully identifies genes informative for cancer classification and provides very reliable cancer classification results.
Should erythromycin be administered before endoscopy for acute upper gastrointestinal hemorrhage

Should erythromycin be administered before endoscopy for acute upper gastrointestinal hemorrhage?
Relationship of Photoperiod to Puberty in Doe Fawn White-Tailed Deer

Experiments on doe fawn white-tailed deer ( Odocoileus virginianus ) in Upper Michigan revealed that artificially long days (16L:8D) in autumn did not induce a greater fertility rate compared to short-day (natural daylight) controls. Eleven (61.1%) of 18 long-day doe fawns became pregnant and carried fawns to term, vs. 8 (72.7%) of 11 short-day controls. However, onset of puberty (i.e., estrus) tended to be delayed among long-day specimens compared to the controls. Data support the concept of a doe fawn's critical fat/lean biomass ratio regulating the temporal onset of puberty. In northern climes, nutritional constraints rather than rapidly diminishing photoperiod probably serve to curtail folliculogenesis, resulting in a low fertility rate among doe fawn deer.
Laparoscopic management of iatrogenic bladder injury and bladder stone formation following laparoscopic inguinal herniorrhaphy

Background Herniorrhaphy is one of the most commonly performed operations in the UK. Approximately 1 per 1,000 of the population has a groin hernia.
Three-Dimensional Monolayers: Voltammetry of Alkanethiolate-Stabilized Gold Cluster Molecules

Voltammetry of nonspecifically adsorbed and of freely diffusing monolayer protected clusters (MPCs) is presented. The MPC monolayers are mixtures of n-octanethiolates and ω-functionalized ferrocenyloctanethiolates. MPC adsorption coverages range from a few percent to roughly a full monolayer of cluster molecules. Rotated disk electrode voltammetry of the ferrocenated MPCs has two principal features: the ferrocene oxidation wave and sloping current baselines at prewave and postwave potentials. Each MPC molecule can have multiple ferrocene units; characteristics of the ferrocene wave indicate that the polyelectron-transfer oxidations occur as a rapid sequence of single electron transfers. Comparisons of different modes of polyelectron transfer suggest that the present one involves rotational diffusion. Deviation from ideal Nernstian one-electron-transfer behavior is modeled as a Gaussian distribution of E0‘ values. The sloping current baselines are attributed to double layer charging of the cluster cores t...
Growth and morphology of single crystals of hexagonal molybdates(IV) M2Mo3O8 (M = Mn, Fe, Co, Ni)

Abstract Chemical vapor transport in the M(II)-Mo(IV)-O system (M = Mn, Fe, Co, Ni) with HCl and TeCl 4 as transporting agents was studied. Crystals of the ternary oxides M 2 Mo 3 O 8 of 2 mm size were grown with TeCl 4 and their morphology was determined. The crystallization of Fe 2 MoO 4 with HCl and of MoO 2 and Te with TeCl 4 was consistent with thermodynamic data predicting a higher transport rate of M in the HCl case and of Mo in the TeCl 4 case. Attack of the silica tubes was severe for M = Mn and Fe.
Development of confocal immunofluorescence FRET microscopy to Investigate eNOS and GSNOR localization and interaction in pulmonary endothelial cells

Confocal FRET microscopy is a widely used technique for studying protein-protein interactions in live or fixed cells. Endothelial nitric oxide synthase (eNOS) and S-nitrosoglutathione reductase (GSNOR) are enzymes involved in regulating the bioavailability of S-nitrosothiols (SNOs) in the pulmonary endothelium and have roles in the development of pulmonary arterial hypertension. Labeling of endogenous proteins to better understand a disease process can be challenging. We have used immunofluorescence to detect endogenous eNOS and GSNOR in primary pulmonary endothelial cells to co-localize these proteins as well as to study their interaction by FRET. The challenge has been in selecting the right immunofluorescence labeling condition, right antibody, the right blocking reagent, the right FRET pair and eliminating cross-reactivity of secondary antibodies. We have used Alexa488 and Alexa568 as a FRET pair. After a series of optimizations, the data from Confocal Laser Scanning Microscopy (CLSM) demonstrate co-localization of eNOS and GSNOR in the perinuclear region of the pulmonary endothelial cell primarily within the cis-Golgi with lower levels of co-localization seen within the trans-Golgi. FRET studies demonstrate, for the first time, interaction between eNOS and GSNOR in both murine and bovine pulmonary endothelial cells. Further characterization of eNOSGSNOR interaction and the subcellular location of this interaction will provide mechanistic insight into the importance of S-nitrosothiol signaling in pulmonary biology, physiology and pathology.
Geometrical considerations for Compton scatter densitometry

The determination of the physical density by Compton scatter densitometry is dependent upon the geometry used for the measurement. The diameter of the sample, the density range, and the scattering volume size and shape influence the relative electron density values obtained by such a system. This work presents the results of an experimental analysis of these parameters in which the importance of each is evaluated for samples of known density. A bias in the computed Compton density, due to multiple scattering and attenuation, is defined; and an expression relating the density bias to these geometrical parameters is presented. The importance of applying corrections to the computed physical density for samples of large diameter and/or high density (cortical bone tissue and large diameter cancellous bone tissue) is discussed.
Endometritis: The clinical-pathologic syndrome

OBJECTIVE: The purpose of this study was to evaluate histologically proved endometritis as a clinical syndrome that is distinct from laparoscopically confirmed salpingitis. STUDY DESIGN: This was a cross-sectional study of 152 women in an urban hospital with a suspected pelvic inflammatory disease. All women provided a standardized medical history and underwent physical examination, endometrial biopsy, and laparoscopy. We defined endometritis by the presence of plasma cells in endometrial stroma and neutrophils in the endometrial epithelium. RESULTS: Of 152 women who were enrolled, 43 women had neither endometritis nor salpingitis; 26 women had endometritis alone without salpingitis, and 83 women had salpingitis. Those women with endometritis alone more often had couched recently, had a current intrauterine device, and were in menstrual cycle day 1 to 7, compared with women with no endometritis or salpingitis (P = .007, .04, .005, respectively) or women with acute salpingitis (P = .03, .01, .02, respectively). Infection with Neisseria gonorrhoeae and/or Chlamydia trachomatis was found more frequently in women with endometritis alone than in women with no endometritis or salpingitis (P < .001) and less frequently than in women with salpingitis (P = .05). Lower quadrant, adnexal, cervical motion, rebound tenderness, peritonitis, tenderness score, fever, and laboratory abnormalities that indicated inflammation and detection of gonorrheal or chlamydial infection were significantly less common in women with endometritis alone than in women with salpingitis but were somewhat more common in women with endometritis alone than among women with no salpingitis or endometritis. CONCLUSION: Among women with suspected pelvic inflammatory disease, the histopathologic manifestations of endometritis were associated with clinical manifestations, infection, and specific risk factors that were intermediate in frequency between women with salpingitis and women with neither endometritis nor salpingitis.
Re-recession of the medial rectus muscles in patients with recurrent esotropia.

Abstract Purpose: Retrospective evaluation of changes in ocular motility after surgical re-recession of the medial rectus (MR) muscles as treatment of recurrent esotropia (ET). Methods: We describe 115 patients (age, 11 months—77 years; median, 11.1 years; 83 children and 32 adults) with an average amount of non-accommodative ET before surgery of 18.7 PD (SD = 8.8 PD). Preoperative alignment, amount of re-recession, distance from insertion to the limbus, and postoperative alignment and versions were collected. Results: In most cases, MR muscles were re-recessed to a fixed distance of 12 mm from the limbus, with unilateral re-recessions in cases with relatively small ET (typically 20 PD). No clear relation was found between the amount of re-recession and the change in alignment in prism diopters. The success rate (esotropia [ET] ≤ 10 PD or exotropia [XT] ≤ 8 PD) 4 weeks to 8 months after surgery was 85%, with 4 patients still showing ET and 13 patients showing XT. Incidence of XT was higher for bilateral than for unilateral re- recessions. Significant underaction of the MR muscles was noted in 7% of the patients. None of the undercorrected patients and only 1 of the overcorrected patients were adults. Among adults, incidence of MR underaction was 4%. Long-term follow-up (8-120 months; median, 25 months) data from 59 patients indicated that good stability in alignment can be expected. Conclusion: The results support the notion that MR re-recession to 12 mm from the limbus successfully corrects recurrent ET up to 35 PD and that it is particularly effective in adults. (J AAPOS 2001;5:381-7)
SU-FF-T-123: Robust Optimization Including Effects of Systematic Treatment Errors

Purpose: Intensity‐modulated treatment planning methods have not previously accounted for systematic errors in tumor and tissue locations. We introduce a novel method for including systematic errors during the optimization phase, based on estimated probabilities of systematic geometrical shifts or tissue misidentification(i.e.tumor location). Method and Materials: Given a planning geometry, the users supply estimates of the systematic probability that tissues are actually displaced by a given vector(“ensemble”). Overall plan quality is based on probability‐weighted measures of actual plan realization. Ensembles are estimated here based on dose‐convolution with Gaussian probability distributions. Two different objective function metrics based on this paradigm are investigated:the maximum probability of tumor under‐dosage is computed using integer variables which divide dose values into under‐dose vs. adequate dose. Similarly, the probability that dose to a critical serial normal structure will exceed tolerance is formed into an objective function. A third metric is the uncertainty in the mean dose given to the tumor, averaged over ensembles. Both of these can be mixed with other standard metrics in the IMRTtreatment planningoptimization process. Results: Mathematical formulas for the metrics were derived. We demonstrate the use of ensemble averaging using large‐scale mixed integer programming. A systematic setup shift Gaussian probability distribution of 5 mm(half‐width) was assumed. A lung treatment plan was tested partly based on minimizing the highest probability of clinical target volume under‐dosage. The plan was more robust against systematic errors than the comparable plan without considering the robust metric. Conclusion: Systematic uncertainties can be considered directly within the optimization process by averaging over ensembles. The result is increased robustness of the treatment plans. The method of estimating dose to the ensemble treatment plans needs to be studied to potentially improve its accuracy. We have introduced novel metric functions based on explicitly considering the effects of systematic errors, thereby resulting in treatment plans of increased robustness.
Sensitivity Limits of an Optical-Fiber Gyroscope

The optimum sensitivity limits of an optical-fiber gyro are assessed with intrinsic light scattering taken into account. Results reveal that laser wavelength of 1.1 µm is more suitable than 0.633 µm, continuous mode stripping can reduce the scattering effect by one hundredfold, and photon-noise-limited performance can be achieved with the adoption of modulation or heterodyne techniques. Numerical examples show that sensitivities of 0.0078 deg/h at 2 mW laser power and 0.0009 deg/h at 81 mW for X=0.633 Âµm, and 0.0025 deg/h at 2 mW and 0.0007 deg/h at 14.4 mW for X=1.1 pm may be achieved. These values are better than those of the current ring laser gyros and suggest that, with adequate research and development effort, the optical fiber gyroscope canlpeaviable alternative to ring laser gyros as high-performance rotational rate sensors.© (1978) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.