cssi/SciSciGPT-SciSciNet huggingface dataset:
Investigation of dried blood sampling with liquid chromatography tandem mass spectrometry to confirm human exposure to nerve agents.

Abstract A method was developed to detect and quantify organophosphate nerve agent (OPNA) metabolites in dried blood samples. Dried blood spots (DBS) and microsampling devices are alternatives to traditional blood draws, allowing for safe handling, extended stability, reduced shipping costs, and potential self-sampling. DBS and microsamplers were evaluated for precision, accuracy, sensitivity, matrix effects, and extraction recovery following collection of whole blood containing five OPNA metabolites. The metabolites of VX, Sarin (GB), Soman (GD), Cyclosarin (GF), and Russian VX (VR) were quantitated from 5.0 to 500 ng mL−1 with precision of ≤16% and accuracy between 93 and 108% for QC samples with controlled volumes. For unknown spot volumes, OPNA metabolite concentrations were normalized to total blood protein to improve interpretation of nerve agent exposures. This study provides data to support the use of DBS and microsamplers to collect critical exposure samples quickly, safely, and efficiently following large-scale chemical exposure events.
Cancer core length from targeted biopsy: an index of prostate cancer volume and pathological stage

Objective To study the relationship of maximum cancer core length (MCCL), on targeted biopsy (TB) of magnetic resonance imaging (MRI)-visible index lesions, to volume of that tumour found at radical prostatectomy (RP). Patients and methods In all, 205 men undergoing fusion biopsy and RP were divided into two groups: 136 in whom the MCCL came from an index MRI-visible lesion (TB) and 69 in whom MCCL came from a non-targeted lesion (non-targeted biopsy [NTB]). MRI was 3-T multi-parametric and biopsy was via MRI-ultrasonography fusion. Results In the TB group, MCCL correlated with volume of clinically significant index tumours (ρ = 0.44-0.60, P 10 mm) and MRI lesion diameter (>20 mm) were independently associated with tumour volume. TB MCCLs >10 mm and Gleason scores >7 were each associated with pathological T3 disease (odds ratios 5.73 and 5.04, respectively), but MRI lesion diameter lesion was not. Conclusions MCCL on a TB from an MRI-visible lesion is an independent predictor of both cancer volume and pathological stage. This relationship does not exist for MCCL from a NTB core. Quantifying CCL on MRI-TBs may have a value, not previously described, to risk-stratify patients with prostate cancer before treatment.
Prostate cancer detection from multi-institution multiparametric MRIs using deep convolutional neural networks system (Erratum)

This erratum corrects an error in the article, “Prostate cancer detection from multi-institution multiparametric MRIs using deep convolutional neural networks system,” by Y. Sumathipala et al.
Assessment of Combined Nivolumab and Bevacizumab in Relapsed Ovarian Cancer: A Phase 2 Clinical Trial

Importance To date, single-agent programmed cell death 1 protein 1 (PD-1)/programmed death ligand 1 (PD-L1) immune checkpoint blockade has shown limited activity in recurrent epithelial ovarian cancer. Combination strategies of PD-1/PD-L1 inhibition with antiangiogenic therapy have the potential for synergistic activity through modulation of the microenvironment and represent a potential therapeutic opportunity in this disease. Objective To evaluate the activity of combined nivolumab and bevacizumab in women with relapsed ovarian cancer. Design, Setting, and Participants A single-arm, phase 2 study enrolled patients between February 8, 2017, and December 29, 2017, at 2 sites in the United States; the primary data analysis was completed July 27, 2018. Thirty-eight women with relapsed epithelial ovarian cancer were enrolled in this study. Participants had disease recurrence within 12 months of their last platinum-based therapy and had received between 1 and 3 lines of prior therapy. Interventions Participants received intravenous nivolumab and intravenous bevacizumab once every 2 weeks. Main Outcome and Measures The primary end point was objective response rate (ORR) as measured by Response Evaluation Criteria in Solid Tumors 1.1. Secondary end points included evaluation of the ORR by platinum sensitivity, assessment of progression-free survival, assessment of safety data, and investigation of the association of tumor PD-L1 with response to therapy. Results Of the 38 women enrolled, 18 had platinum-resistant and 20 had platinum-sensitive disease; mean (SD) age was 63.0 (9.1) years. Eleven patients experienced a confirmed response to nivolumab with bevacizumab (ORR, 28.9%; 95% exact binomial CI, 15.4%-45.9%), with 1 additional unconfirmed response. The ORR was 40.0% (19.1%-64.0%) in platinum-sensitive and 16.7% (95% CI 3.6%-41.4%) in platinum-resistant participants. Thirty-four participants (89.5%) experienced at least 1 treatment-related adverse event; 9 participants (23.7%) experienced a grade 3 or higher treatment-related adverse event. Median progression-free survival was 8.1 months (95% CI, 6.3-14.7 months). In 36 histologic samples for which PD-L1 testing could be performed, 22 samples (61.1%) had a PD-L1 tumoral percentage less than 1, and 14 samples (38.9%) had a PD-L1 tumoral percentage of 1 or greater. Ten responses occurred in patients with PD-L1 tumor percentage less than 1, and 2 in patients with PD-L1 tumor percentages of 1 or greater. Conclusions and Relevance The nivolumab with bevacizumab combination appeared to show activity in patients with relapsed ovarian cancer, with greater activity in the platinum-sensitive setting. Alternative combinational strategies may be necessary in the platinum-resistant setting.
Evaluating resilience as a predictor of outcomes in lung transplant candidates.

Background Resilience represents the capacity to adapt to adversity. Resilience can improve following behavioral interventions. We examined lung transplant candidates' resilience as a novel predictor using the Connor-Davidson Resilience Scale (RISC-10). Methods Waitlisted candidates at six centers were mailed questionnaires from 9/16/2015 to 10/1/2019. Follow-up surveys were collected annually and post-transplant. Outcomes were recorded through February 17, 2020. Primary outcome was pre-transplant death/delisting. Analyses included t test or chi-square for group comparisons, Pearson's correlation coefficients for strength of relationships, and Cox proportional-hazard models to evaluate associations with outcomes, adjusting for age, sex, and mood. Results Participation was 55.3% (N = 199). Baseline RISC-10 averaged 32.0 ± 5.6 and did not differ by demographics, primary transplant diagnosis, or disease severity markers. RISC-10 did not correlate to the commonly utilized Psychosocial Assessment of Candidates for Transplant [PACT] or Stanford Integrated Psychosocial Assessment for Transplantation [SIPAT] tools. Scores 1 standard deviation below population average) occurred in 16% and were associated with pre-transplant death or delisting, adjusted Hazard Ratio of 2.60 (95% Confidence Interval 1.23-5.77; P = .01). Conclusion One in six lung candidates had low resilience, predicting increased pre-transplant death/delisting. RISC-10 did not correlate with PACT or SIPAT; resilience may represent a novel risk factor.
ATP-dependent transport of glutathione conjugate of 7β,8α-dihydroxy-9α,10α-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene in murine hepatic canalicular plasma membrane vesicles

Glutathione (GSH) S-transferases (GSTs) have an important role in the detoxification of (+)-anti-7,8-dihydroxy-9,10-oxy-7,8,9, 10-tetrahydrobenzo[a]pyrene [(+)-anti-BPDE], which is the ultimate carcinogen of benzo[a]pyrene. However, the fate and/or biological activity of the GSH conjugate of (+)-anti-BPDE [(-)-anti-BPD-SG] is not known. We now report that (-)-anti-BPD-SG is a competitive inhibitor (Ki 19 microM) of Pi-class isoenzyme mGSTP1-1, which among murine hepatic GSTs is most efficient in the GSH conjugation of (+)-anti-BPDE. Thus the inhibition of mGSTP1-1 activity by (-)-anti-BPD-SG might interfere with the GST-catalysed GSH conjugation of (+)-anti-BPDE unless one or more mechanisms exist for the removal of the conjugate. The results of the present study indicate that (-)-anti-BPD-SG is transported across canalicular liver plasma membrane (cLPM) in an ATP-dependent manner. The ATP-dependent transport of (-)-anti-[3H]BPD-SG followed Michaelis-Menten kinetics (Km 46 microM). The ATP dependence of the (-)-anti-BPD-SG transport was confirmed by measuring the stimulation of ATP hydrolysis (ATPase activity) by the conjugate in the presence of cLPM protein, which also followed Michaelis-Menten kinetics. In contrast, a kinetic analysis of ATP-dependent uptake of the model conjugate S-[3H](2,4-dinitrophenyl)-glutathione ([3H]DNP-SG) revealed the presence of a high-affinity and a low-affinity transport system in mouse cLPM, with apparent Km values of 18 and 500 microM respectively. The ATP-dependent transport of (-)-anti-BPD-SG was inhibited competitively by DNP-SG (Ki 1.65 microM). Likewise, (-)-anti-BPD-SG was found to be a potent competitive inhibitor of the high-affinity component of DNP-SG transport (Ki 6.3 microM). Our results suggest that GST-catalysed conjugation of (+)-anti-BPDE with GSH, coupled with ATP-dependent transport of the resultant conjugate across cLPM, might be the ultimate detoxification pathway for this carcinogen.
The Military Biomedical Complex: Are Service Members a Vulnerable Population?

In the realm of research with human subjects, vulnerability is an elusive concept. Its essence lies in an asymmetry — of information, access, status, power, or control. Yet vulnerability is also context-dependent, meaning a person becomes vulnerable to something when placed in a certain situation. While there is widespread agreement that research guidelines should provide protections for those who are vulnerable, there is less consensus on who is encompassed by the term and what protections are appropriate. In the United States, regulatory guidelines take a categorical approach to defining vulnerability — federal protections identify prisoners, children, neonates, human fetuses, and pregnant women as vulnerable populations, and specify additional protections for research that includes participants from these groups. This Article examines the notion of vulnerability in human subjects research as it applies to members of the armed forces.
Drug Transaction Experiences in American High Schools 2001‐2015

Background Among adolescents, the pathway from being offered drugs to engaging in drug use has been established. The prevalence of drug transactions specifically in schools is less understood. The purpose of this study was to identify the prevalence of adolescents who have reported drug transaction experiences (being offered, sold, or given an illegal drug) on school property and subsequently identify behavioral correlates associated with these experiences. Methods This study analyzed YRBS data from 2001 to 2015 (N = 117,815). We used 95% confidence intervals to evaluate differences in prevalence across years and demographic subgroups. Odds ratios determined the likelihood of engaging in risk behaviors among those youth also experiencing drug transactions on school property. Results Every survey year, at least 1 in 5 youth reported having drug transaction experiences at school. Boys consistently reported significantly higher rates of drug transaction experiences in comparison to girls, with Hispanic boys representing the highest rates. Youth reporting these experiences with drug transactions were also more likely to carry a weapon to school and to be bullied at school. Conclusions Implications for the reduction of drug transactions in high schools are discussed and recommendations for prevention efforts addressing youth engagement in multiple risk behaviors are identified.
CO2 utilization in built environment via the PCO2 swing carbonation of alkaline solid wastes with different mineralogy

Carbon mineralization to solid carbonates is one of the reaction pathways that can not only utilize captured CO2 but also potentially store it in the long term. In this study, the dissolution and carbonation behaviors of alkaline solid wastes (i.e., waste concrete) was investigated. Concrete is one of the main contributors to a large carbon emission in the built environment. Thus, the upcycling of waste concrete via CO2 utilization has multifaceted environmental benefits including CO2 emission reduction, waste management and reduced mining. Unlike natural silicate minerals such as olivine and serpentine, alkaline solid wastes including waste concrete are highly reactive, and thus, their dissolution and carbonation behaviors vary significantly. Here, both conventional acid (e.g., hydrochloric acid) and less studied carbonic acid (i.e., CO2 saturated water) solvent systems were explored to extract Ca from concrete. Non-stoichiometric dissolution behaviors between Ca and Si were confirmed under far-from-equilibrium conditions (0.1 wt% slurry density), and the re-precipitation of the extracted Si was observed at near-equilibrium conditions (5 wt% slurry density), when the Ca extraction was performed at a controlled pH of 3. These experiments, with a wide range of slurry densities, provided valuable insight into Si re-precipitation phenomena and its effect on the mass transfer limitation during concrete dissolution. Next, the use of the partial pressure of CO2 for the pH swing carbon mineralization process was investigated for concrete, and the results were compared to those of Mg-bearing silicate minerals. In the PCO2 swing process, the extraction of Ca was significantly limited by the precipitation of the carbonate phase (i.e., calcite), since CO2 bubbling could not provide a low enough pH condition for concrete–water–CO2 systems. Thus, this study showed that the two-step carbon mineralization via PCO2 swing, that has been developed for Mg-bearing silicate minerals, may not be viable for highly reactive Ca-bearing silicate materials (e.g., concrete). The precipitated calcium carbonate (PCC) derived from waste concrete via a pH swing process showed very promising results with a high CO2 utilization potential as an upcycled construction material.
The Mediator complex kinase module is necessary for fructose regulation of liver glycogen levels through induction of glucose-6-phosphatase catalytic subunit (G6pc).

Abstract Objective Liver glycogen levels are dynamic and highly regulated by nutrient availability as the levels decrease during fasting and are restored during the feeding cycle. However, feeding in the presence of fructose in water suppresses glycogen accumulation in the liver by upregulating the expression of the glucose-6-phosphatase catalytic subunit (G6pc) gene, although the exact mechanism is unknown. We generated liver-specific knockout MED13 mice that lacked the transcriptional Mediator complex kinase module to examine its effect on the transcriptional activation of inducible target gene expression, such as the ChREBP- and FOXO1-dependent control of the G6pc gene promoter. Methods The relative changes in liver expression of lipogenic and gluconeogenic genes as well as glycogen levels were examined in response to feeding standard low-fat laboratory chow supplemented with water or water containing sucrose or fructose in control (Med13fl/fl) and liver-specific MED13 knockout (MED13-LKO) mice. Results Although MED13 deficiency had no significant effect on constitutive gene expression, all the dietary inducible gene transcripts were significantly reduced despite the unchanged insulin sensitivity in the MED13-LKO mice compared to that in the control mice. G6pc gene transcription displayed the most significant difference between the Med13 fl/fl and MED13-LKO mice, particularly when fed fructose. Following fasting that depleted liver glycogen, feeding induced the restoration of glycogen levels except in the presence of fructose. MED13 deficiency rescued the glycogen accumulation defect in the presence of fructose. This resulted from the suppression of G6pc expression and thus G6PC enzymatic activity. Among two transcriptional factors that regulate G6pc gene expression, FOXO1 binding to the G6pc promoter was not affected, whereas ChREBP binding was dramatically reduced in MED13-LKO hepatocytes. In addition, there was a marked suppression of FOXO1 and ChREBP-β transcriptional activities in MED13-LKO hepatocytes. Conclusions Taken together, our data suggest that the kinase module of the Mediator complex is necessary for the transcriptional activation of metabolic genes such as G6pc and has an important role in regulating glycogen levels in the liver through altering transcription factor binding and activity at the G6pc promoter.
Solving a class of feature selection problems via fractional 0–1 programming

Feature selection is a fundamental preprocessing step for many machine learning and pattern recognition systems. Notably, some mutual-information-based and correlation-based feature selection problems can be formulated as fractional programs with a single ratio of polynomial 0–1 functions. In this paper, we study approaches that ensure globally optimal solutions for these feature selection problems. We conduct computational experiments with several real datasets and report encouraging results. The considered solution methods perform well for medium- and reasonably large-sized datasets, where the existing mixed-integer linear programs from the literature fail.
Phenotypic and Genetic Spectrum of Autosomal Recessive Bestrophinopathy and Best Vitelliform Macular Dystrophy.

Purpose Autosomal recessive bestrophinopathy (ARB) and vitelliform macular dystrophy (VMD) are distinct phenotypes, typically inherited through recessive and dominant patterns, respectively. Recessively inherited VMD (arVMD) has been reported, suggesting that dominant and recessive BEST1-related retinopathies represent a single disease spectrum. This study compares adVMD, arVMD, and ARB to determine whether a continuum exists and to define clinical and genetic features to aid diagnosis and management. Methods One arVMD patient and nine ARB patients underwent standard ophthalmic examination, imaging, electrophysiology, and genetic assessments. A meta-analysis of reported BEST1 variants was compiled, and clinical parameters were analyzed with regard to inheritance and phenotype. Results Among 10 patients with biallelic BEST1 variants, three novel ARB variants (p.Asp118Ala, p.Leu224Gln, p.Val273del) were discovered. A patient with homozygous p.Glu35Lys was clinically unique, presenting with VMD, including hyperautofluorescence extending beyond the macula, peripheral punctate lesions, and shortened axial-length. A tritan-axis color vision deficit was seen in three of six (50%) of ARB patients. Attempts to distinguish recessively-inherited ARB and dominantly-inherited VMD genotypically, by variant frequency and residue location, did not yield significant differences. Literature meta-analysis with principle component analysis of clinical features demonstrated a spectrum of disease with arVMD falling between adVMD and ARB. Conclusions This study suggests that arVMD is part of a continuum of autosomal recessive and dominant BEST1-related retinopathies. Detailed clinical and molecular assessments of this cohort and the literature are corroborated by unsupervised analysis, highlighting the overlapping heterogeneity among BEST1-associated clinical diagnoses. Tritan-axis color vision deficit is a previously unreported finding associated with ARB.
Spectroscopic Analysis of Hormone in Thin Films

More rapid, reproducible, and cost-effective methods to quality control products in the pharmaceutical industry continue to be a major emphasis. Many different methods have been used to determine the stability and content uniformity of a drug in various dosage forms; however most of these methods include the destruction of the sample. Therefore, the development of nondestructive methods has become the basis of much research. A new assay for the nondestructive determination of testosterone content in mucoadhesive bi-layer thin-film composites (TFCs) using near-infrared spectroscopy (NIR) was developed. Five sets of the circular films (n=5) with theoretical testosterone content of 0 mg, 1 mg, 2 mg, 3 mg, and 4 mg per 3/8 inch diameter disks were scanned in the near-infrared region of 1100 to 2500 nm to determine testosterone content. The NIR results were directly compared to those obtained using a previously developed ultraviolet assay for testosterone at 240 nm. Principal component regression (PCR) was performed to determine the accuracy of the new NIR assay. This correlation resulted in a r value of 0.98869 with an error of 0.19 mg. Though the UV assay showed a better r value, the NIR assay was much quicker, easier, and nondestructive. Therefore, the NIR assay may have significant potential for its use in the quality control of pharmaceutical films containing drugs.
OIDM: online interactive data mining

Facilitated by the achievements of various data mining techniques, both academic research and industrial applications are using data mining tools to explore knowledge from various databases. However, building a mining system is a nontrivial task, especially for a data mining novice. In this paper, we present an online interactive data mining toolbox - OIDM, which provides three categories (classification, association analysis, and clustering) of data mining tools, and interacts with the user to facilitate his/her mining process. The interactive mining is accomplished through interviewing the user about his/her data mining task. OIDM can help the user find the appropriate mining algorithm, refine the mining process, and finally get the best mining results. To evaluate the system, the website of OIDM (2003) has been released. The feedback is positive. Both students and senior researchers found that OIDM would be useful in conducting data mining research. This research is supported by a NASA EPSCoR grant.
Reactive oxygen species contribute to the development of arrhythmogenic Ca2+ waves during β-adrenergic receptor stimulation in rabbit cardiomyocytes

While β-adrenergic receptor (β-AR) stimulation leads to positive inotropic effects, it can also induce arrhythmogenic Ca2+ waves. β-AR stimulation increases mitochondrial oxygen consumption and, thereby, the production of reactive oxygen species (ROS). We therefore investigated the role of ROS in the generation of Ca2+ waves during β-AR stimulation in rabbit ventricular myocytes. Isoproterenol (ISO) increased Ca2+ transient amplitude during systole, sarcoplasmic reticulum (SR) Ca2+ load and the occurrence of Ca2+ waves during diastole. These effects, however, developed at different time points during ISO application. While SR Ca2+ release and load reached a maximum level after 3 min, Ca2+ waves occurred at the highest frequency only after 6 min of ISO application. Measurement of intra-SR-free Ca2+ concentration ([Ca2+]SR) showed an initial increase of SR Ca2+ load followed by a gradual decline over time during ISO application. This decline of [Ca2+]SR was not due to decreased SR Ca2+ uptake, but instead was the result of increased SR Ca2+ leak mainly in the form of Ca2+ waves. ISO application led to significant RyR phosphorylation at the protein kinase A (PKA)-specific site, which remained relatively stable throughout β-AR activation. Moreover, β-AR stimulation significantly increased ROS production after 4–6 min of ISO application. The ROS scavenger Tiron and the superoxide dismutase mimetic MnTBPA abolished the ISO-mediated ROS production. The mitochondria-specific antioxidant Mito-Tempo and an inhibitor of the electron transport chain, rotenone, also effectively prevented the ISO-mediated ROS production. Scavenging ROS during ISO application decreased the occurrence of Ca2+ waves and partially prevented augmentation of SR Ca2+ leak, but did not affect the increase of Ca2+ transient amplitude. Treatment of myocytes with ISO for 15 min significantly reduced the free thiol content in RyRs. These data suggest that increased mitochondrial ROS production during β-AR stimulation causes RyR oxidation. Together with RyR phosphorylation, oxidation of RyRs increases diastolic SR Ca2+ leak to a critical level leading to the generation of arrhythmogenic Ca2+ waves.
A hybrid method for planning and scheduling

We combine mixed integer linear programming (MILP) and constraint programming (CP) to solve planning and scheduling problems. Tasks are allocated to facilities using MILP and scheduled using CP, and the two are linked via logic-based Benders decomposition. Tasks assigned to a facility may run in parallel subject to resource constraints (cumulative scheduling). We solve minimum cost problems, as well as minimum makespan problems in which all tasks have the same release date and deadline. We obtain computational speedups of several orders of magnitude relative to the state of the art in both MILP and CP.
Spinal adenosine A2A receptor inhibition enhances phrenic long term facilitation following acute intermittent hypoxia

Phrenic long term facilitation (pLTF) is a form of respiratory plasticity induced by acute intermittent hypoxia. pLTF requires spinal serotonin receptor activation, new BDNF synthesis and TrkB receptor activation. Spinal adenosine 2A (A2A) receptor activation also elicits phrenic motor facilitation, but by a distinct mechanism involving new TrkB synthesis. Because extracellular adenosine increases during hypoxia, we hypothesized that A2A receptor activation contributes to acute intermittent hypoxia (AIH)-induced pLTF. A selective A2A receptor antagonist (MSX-3, 8 μg kg−1, 12 μl) was administered intrathecally (C4) to anaesthetized, vagotomized and ventilated male Sprague–Dawley rats before AIH (three 5 min episodes, 11% O2). Contrary to our hypothesis, pLTF was greater in MSX-3 versus vehicle (aCSF) treated rats (97 ± 6%vs. 49 ± 4% at 60 min post-AIH, respectively; P 0.05). A second A2A receptor antagonist (ZM2412385, 7 μg kg−1, 7 μl) enhanced pLTF (85 ± 11%, P 0.05), indicating specific A2A receptor effects. Intrathecal methysergide (306 μg kg−1, 15μl) blocked AIH-induced pLTF in both MSX-3 and aCSF treated rats, confirming that enhanced pLTF is serotonin dependent. Intravenous MSX-3 (140 μg kg−1, 1 ml) enhanced both phrenic (104 ± 7%vs. 57 ± 5%, P < 0.05) and hypoglossal LTF (46 ± 13%vs. 28 ± 10%; P < 0.05). In conclusion, A2A receptors constrain the expression of serotonin-dependent phrenic and hypoglossal LTF following AIH. A2A receptor antagonists (such as caffeine) may exert beneficial therapeutic effects by enhancing the capacity for AIH-induced respiratory plasticity.
Biopsy vs. extensive resection for first recurrence of glioblastoma: is a prospective clinical trial warranted?

Glioblastoma is an aggressive and almost universally fatal tumor. The prognosis at the time of recurrence has generally been poor, with overall survival typically in the range of 4–40 weeks. The merits of surgical resection (vs. open biopsy, to confirm recurrence via histology) in addition to conventional adjuvant chemotherapy have been the subject of longstanding debate. We wondered whether it would possible to conduct a trial at our institution to settle this question definitively with Class I evidence. Initially, we had hoped to conduct a randomized, unblinded prospective clinical trial. However on closer inspection it appeared that such an undertaking would pose significant practical challenges. Thus we present our protocol in draft form. In keeping with recommended outcomes for these tumors, the primary endpoint would be median progression free survival. Secondary end points would be: median overall survival (mOS, from time of recurrence) and change in Karnofsky Performance Status over time. Patients would be eligible at the time of first recurrence if they had received conventional treatment until that point and at least 1 month had elapsed since the time of radiation. All patients would be considered potentially eligible for enrollment (unless the decision regarding resection was already clear-cut in view of other factors). Using Cox’s proportional hazards model, we estimate that at least 456 patients would be necessary to demonstrate an increase in the hazard ratio to 1.3 for those undergoing biopsy alone. This magnitude of benefit is estimated based on a review of retrospective studies. If restricted to our Institution alone, which sees approximately 100–150 new cases of glioblastoma each year, a trial of this nature would be likely to take around 10 years. Furthermore, there may be significant reluctance on the part of patients and physicians to participate. There is also the opportunity cost of excluding patients from other trials to consider. We recognize that the estimate of the magnitude of effect may be conservative. As things stand, we feel that multi-institutional collaboration would almost certainly be required for an undertaking of this kind.
Improved cross-axis synchronous flow-through coil planet centrifuge for performing counter-current chromatography

Abstract A novel design of the cross-axis synchronous flow-through coil planet centrifuge is introduced. The apparatus holds a pair of large coil holders symmetrically, one on each side of the rotary frame, at a lateral position 12.5 cm from the center of the holder shaft held 10 cm from the centrifuge axis. Mathematical analysis of acceleration generated by the planetary motion of the apparatus revealed a unique centrfugal force field which promises high retention of the stationary phase in the multilayer coil to perform efficient preparative-scale counter-current chromatography.
Teaching Astronomy and the Vital Role of the True Amateur

This contribution summarized the situation in the United Kingdom where there are 5 organisations that are concerned with astronomical observation, but where there are hopes that a single unifying committee may be formed. Practical work for pupils was essential and many examples of simple equipment and practical applications were shown.
Exact algorithm for sampling the two-dimensional Ising spin glass.

A sampling algorithm is presented that generates spin-glass configurations of the two-dimensional Edwards-Anderson Ising spin glass at finite temperature with probabilities proportional to their Boltzmann weights. Such an algorithm overcomes the slow dynamics of direct simulation and can be used to study long-range correlation functions and coarse-grained dynamics. The algorithm uses a correspondence between spin configurations on a regular lattice and dimer (edge) coverings of a related graph: Wilson's algorithm [D. B. Wilson, Proceedings of the Eighth Symposium on Discrete Algorithms (SIAM, Philadelphia, 1997), p 258] for sampling dimer coverings on a planar lattice is adapted to generate samplings for the dimer problem corresponding to both planar and toroidal spin-glass samples. This algorithm is recursive: it computes probabilities for spins along a ``separator'' that divides the sample in half. Given the spins on the separator, sample configurations for the two separated halves are generated by further division and assignment. The algorithm is simplified by using Pfaffian elimination rather than Gaussian elimination for sampling dimer configurations. For $n$ spins and given floating point precision, the algorithm has an asymptotic run-time of $O({n}^{3/2})$; it is found that the required precision scales as inverse temperature and grows only slowly with system size. Sample applications and benchmarking results are presented for samples of size up to $n={128}^{2}$, with fixed and periodic boundary conditions.
The Civic Education of Cicero’s Ideal Orator

Scarcely five years after the Roman people hailed him as “father of the fatherland” for his role in saving the Republic from a revolutionary plot, Cicero was banished from Rome. A violent and demagogic tribune, backed by a cabal of ruthless senators including Julius Caesar and Pompey the Great, had arranged for his removal. Though he would return the following year, Rome’s leading orator increasingly found himself politically hamstrung and the republican system plagued by dysfunction. Intent on remedying the ills of the Republic, Cicero took to writing philosophy.
Developmental Psychopathology and Preventive Intervention

This chapter focuses on two high-risk groups, including children with histories of maltreatment and the offspring of mothers with a major depressive disorder, in order to illustrate how theory and research guided by a developmental psychopathology perspective can inform the implementation, conduct, and evaluation of preventive interventions for high-risk conditions. Two preventive intervention programs are described in detail and they serve as case studies to illustrate the process involved with designing preventive interventions, recruiting the samples, and dealing with the interface between the research and clinical worlds. Throughout the chapter, decision points and challenges that emerge during the development, implementation, and evaluation of these preventive interventions are discussed. Issues that are likely to be encountered in translating efficacy-based clinical trials into broader clinical contexts also are addressed. Keywords: bridging research and practice; child maltreatment; developmental psychopathology; maternal depression; organizational perspective on development; preventive interventions; translational research
Efficient systolic array implementations of digital filtering

Four different realization schemes are proposed to improve hardware efficiency for the systolic array implementation of a general class of IIR digital filters that includes the classical direct-form digital filter, the Gray-Markel digital lattice or ladder filters, and the Rao-Kailath orthogonal digital filters. The four schemes use: (1) two interleaved-signal sequences; (2) two-module processing elements (PEs); (3) two overlapped cascaded smaller filters; and (4) a systolic ring. Each scheme has its own advantages and disadvantages. The first scheme can always achieve 100% hardware utilization, but it only applies to the digital filtering of two data sequences. The second scheme is simple and straightforward, but it needs more multiplexers than the other schemes. The third scheme needs only one multiplexer, but the transfer function has to be factorized. The fourth scheme also needs only one multiplexer, but it can have more half-active PEs in some cases. Which scheme is preferable depends on specific situations and applications. Generally speaking, all four of these proposed schemes can improve the hardware efficiency to (or near) 100% with low control overhead. >
Nicotine attenuates spatial learning deficits induced in the rat by perinatal lead exposure

Maternally lead (Pb)-exposed, juvenile rats exhibit significant deficits in spatial reference memory acquisition and working memory performance in the Morris water maze (MWM). Acute systemic application of nicotine reverses these deficits without affecting behavioral performance of the age-matched, lead-unexposed control animals. These results suggest that nicotinic agonist treatments can ameliorate learning and memory impairments, presumably by compensating for deficient nicotinic function in developmentally lead-exposed animals.
The Synoptic-Scale Environment Associated with the Low-Level Jet of the Great Plains

Abstract The synoptic-scale conditions of the upper- and lower-tropospheric circulation and water vapor transport during the occurrence of the low-level jet (LLJ) over the Great Plains were analyzed in terms of composite Stream- and potential functions for 64 cases over a period of 11 springs (1979–89). The LLJ formation takes place when a developing baroclinic wave with an upper-level jet appears east of the Rocky Mountains. The divergent circulation associated with this baroclinic wave exhibits the coupling of the upper-tropospheric divergence with the lower-level convergence ahead of this wave as predicted by the classic baroclinic wave theory. The precipitation generated by severe storms over the surface low northeast of the LLJ is maintained by the water vapor converged by the lower-tropospheric convergence.
Prewetting phase diagram of 4He on cesium.

We have studied the adsorption of $^{4}\mathrm{He}$ on cesium in the temperature range from 1.3 to 4.1 K. The $^{4}\mathrm{He}$ film undergoes a first-order phase transition known as prewetting. The prewetting line intersects the coexistence curve at the wetting temperature, ${\mathit{T}}_{\mathit{w}}$=1.95 K, and terminates at ${\mathit{T}}_{\mathit{c}}$=2.5 K, the prewetting critical point. There are dramatic hysteresis effects when the temperature of the system is varied at coexistence in the vicinity of ${\mathit{T}}_{\mathit{w}}$. This is the first experimental realization of a complete prewetting phase diagram.
Family factors in Internet addiction among Chinese youth: A review of English- and Chinese-language studies

Approximately 513 million Chinese citizens used the Internet in 2011, with adolescents reporting comparatively high levels of use. Although numerous studies (reviewed herein) indicate that Internet Addiction/Pathological Internet Use (IA/PIU) is endemic among Chinese youth and trending upward, no prior review has examined family correlates of IA/PIU in Chinese youth. Thus, our principal aim was to evaluate methodological features and substantive findings of all studies examining family correlates of IA/PIU in Chinese youth. Internet, demographic, psychosocial, and psychiatric/behavioral correlates of IA/PIU, and prevalence estimates for adolescent IA/PIU, were also examined using the large set of studies evaluated in association with our principal aim. Comprehensive bibliographic searches identified 42 pertinent investigations. Youth with IA/PIU reported greater global dissatisfaction with their families; less organized, cohesive and adaptable families; greater inter-parental and parent-child conflict; and perceived their parents as more punitive, and less supportive, warm, and involved compared to non-IA youth. IA/PIU youth were significantly more likely to have divorced parents, live with a single parent, and be an only child than non-IA/PIU youth. IA/PIU is prevalent among Chinese youth and associated with diverse family, psychosocial and psychiatric/behavioral impairments, but rarely is the focus of prevention and treatment interventions.
A butterfly processor-memory interconnection for a vector processing environment

Abstract A fundamental hurdle impeding the development of large N common memory multiprocessors is the performance limitation incurred in the switch connecting the processors to the memory modules. Multistage networks currently considered for this connection have a memory latency which grows like αlog2N. For scientific computing, it is natural to look for a multiprocessor architecture that will enable the use of vector operations to mask memory latency. The problem to be overcome here is the chaotic behavior introduced by conflicts occurring in the switch. In this paper we examine the performance of the butterfly or indirect binary n-cube network in a vector processing environment. We describe a simplemodification of the standard 2 × 2 switch node used in such networks. This local modification to the switch node endows the network with a surprising global property. It adaptively removes chaotic behavior during a vector operation.
Single cell trapping in larger microwells capable of supporting cell spreading and proliferation

Conventional cell trapping methods using microwells with small dimensions (10–20 μm) are useful for examining the instantaneous cell response to reagents; however, such wells have insufficient space for longer duration screening tests that require observation of cell attachment and division. Here we describe a flow method that enables single cell trapping in microwells with dimensions of 50 μm, a size sufficient to allow attachment and division of captured cells. Among various geometries tested, triangular microwells were found to be most efficient for single cell trapping while providing ample space for cells to grow and spread. An important trapping mechanism is the formation of fluid streamlines inside, rather than over, the microwells. A strong flow recirculation occurs in the triangular microwell so that it efficiently catches cells. Once a cell is captured, the cell presence in the microwell changes the flow pattern, thereby preventing trapping of other cells. About 62% of microwells were filled with single cells after a 20 min loading procedure. Human prostate cancer cells (PC3) were used for validation of our system.
Prevalence of leukemia in hemolymph of soft-shell clams, Mya arenaria, in Dorchester Bay, Boston Harbor

Abstract Four sites in Dorchester Bay, Boston Harbor were selected to gather baseline data on the prevalence of leukemia in soft-shell clams. Mya arenaria. Prevalence studies were conducted from September 1986 to December 1987 using two techniques to evaluate hemolymph: (1) Indirect immunoperoxidase (IP) staining using monoclonal antibodies specific for leukemic cells of Mya, (2) Feulgen-picromethyl blue (FPMB) staining. Tissue samples were also obtained from some clams for histopathological examination. The results show that there is no statistically different prevalence of leukemia in any, of the four sites studied. In addition, there is no seasonal pattern in the prevalence of disease. The prevalence of the leukemia in Boston Harbor is similar to natural background levels; however, gill inflammation and hyperplasia are elevated.
Mutagenesis induced by the tumor microenvironment

Genomic instability is a commonly observed feature of tumors. Most investigations addressing the mechanism of tumor progression have focused on the genetic factors that may play a role. Growing evidence now suggests that, in addition to these endogenous factors, the exogenous environment within solid tumors may by itself be mutagenic and constitute a significant source of genetic instability. The tumor microenvironment is characterized by regions of fluctuating hypoxia, low pH, and nutrient deprivation. Each of these microenvironmental factors has been shown to cause severe disturbance in cell metabolism and physiology. Both in vivo and in vitro data demonstrate that exposure of tumor cells to adverse conditions can directly cause mutations, contributing to genetic instability. In this review, we will reexamine the current body of evidence on the role of the tumor microenvironment in inducing mutagenesis and consequent tumor progression.
Novel structure-recognition-based OCR system and its parallel VLSI architecture

We propose a structure pattern recognition based OCR system for printed text recognition. The segmentation algorithm is a raster-scan based one that reduces memory access time a great deal. The feature extract algorithm is a chain-code encoding based graph traversal algorithm. It has an advantage of single memory access for each pixel while most graph traversal algorithms require multiple scans of the entire image. While traversing a thinned character, structural feature is automatically extracted. The classification is a process of tree search in the structure feature space that is created during the training process. The segmentation, thinning, and feature extraction algorithms are all raster-scan based algorithms that can be implemented by a parallel systolic array architecture.© (1993) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Impact of Fixture Design Sheet Metal Assembly Variation

This paper presents a new fixture design methodology for sheet metal assembly processes. The proposed approach focuses on the impact of fixture position on the dimensional quality of sheet metal parts after assembly, considering part and tooling variation and assembly springback. The optimization algorithm combines finite element analysis and nonlinear programming methods to find the optimal fixture position such that the assembly variation is minimized. The optimal fixture design methodology enables to significantly reduce the assembly variation in the presence of part and tooling variation. A case study is presented to demonstrate the design procedure.Copyright © 2002 by ASME
Cytotoxin ("lymphotoxin") mediated target cell lysis: involvement of surface component.

The interaction of cytotoxin with target cells to produce target cell lysis is not understood. Herein reported is the identification of an elutable target mouse fibroblast L cell component which when added to other sensitive L cells enhances their sensitivity to cytotoxin, or which when added to L cells rendered relatively insensitive to cytotoxin by incubation in a lipid depleted media, largely restores their sensitivity to cytotoxin. Extraction of the L cell component is carried out by either trypsinization, scraping or by an incubation of 4–6 hr with the monolayer L cells. The elutable component enhances the susceptibility of target cells to cytotoxin rather than by directly affecting cytotoxin as its effect is dependent on an incubation period with the cells prior to the addition of cytotoxin.
Effects of Online Christian Self-Disclosure on Impression Formation

This experiment examined the effects of online Christian disclosure. Respondents (N = 233) viewed a fictional social networking profile containing one of three levels of Christian disclosure frequency: none, nominal, and extensive. Respondents made few distinctions between nondisclosure and nominal disclosure. Most notably, respondent religiosity moderated impressions. Regardless of disclosure level, religious respondents rated profile owners as more likeable and less stereotypically negative than less religious respondents. The least religious respondents tended to rate the extensively disclosing Christian as least romantically desirable and with more negative stereotyping. The most religious respondents rated the extensively disclosing Christian as most likeable and as most romantically desirable. Christian identity tended to be assumed when not disclosed. Nominal disclosure may constitute a socially acceptable level of online Christian disclosure.
Laryngeal pathology in hearing-impaired children☆

Eighty-five children enrolled in a total communication elementary school for the severe-to-profoundly hearing-impaired were evaluated prospectively to assess the incidence of laryngeal abnormalities. Direct flexible laryngoscopy and indirect mirror laryngoscopy revealed vocal cord nodules in 3 children, omega-shape infantile epiglottis in 3 children, and normal larynges in the remaining 79 children. These findings suggest that severe-to-profoundly hearing-impaired children develop detectable laryngeal pathology at approximately the same frequency as previously reported by others for normal hearing children.
Frequency broadening in laser-induced sparks

Abstract The spectrum of forward scattered radiation resulting from laser-induced air breakdown has been investigated using a single-mode ruby laser and a mode-locked neodymium: glass laser. The broadening observed provides additional evidence for self-focusing mechanism associated with the production of laser sparks.
US-France Exchange Programs for Undergraduate and Graduate Engineers: 10 Years of Lessons Learned

In the context of a capstone engineering design experience, American and French students collaborate on ergonomics and multidisciplinary design projects for industrial sponsors. Grown out of this U.S.-French relationship, a dual-degree graduate program was developed and was the first of its kind at Virginia Tech. Discussion focuses on the methods employed in both programs, results achieved and lessons learned during this 10 year international experiment.