cssi/SciSciGPT-SciSciNet huggingface dataset:
Germline genetic variants in men with prostate cancer and one or more additional cancers.

BACKGROUND Prostate cancer has a significant heritable component, and rare deleterious germline variants in certain genes can increase the risk of the disease. The aim of the current study was to describe the prevalence of pathogenic germline variants in cancer-predisposing genes in men with prostate cancer and at least 1 additional primary cancer. METHODS Using a multigene panel, the authors sequenced germline DNA from 102 men with prostate cancer and at least 1 additional primary cancer who also met ≥1 of the following criteria: 1) age ≤55 years at the time of diagnosis of the first malignancy; 2) rare tumor type or atypical presentation of a common tumor; and/or 3) ≥3 primary malignancies. Cancer family history and clinicopathologic data were independently reviewed by a clinical genetic counselor to determine whether the patient met established criteria for testing for a hereditary cancer syndrome. RESULTS Sequencing identified approximately 3500 variants. Nine protein-truncating deleterious mutations were found across 6 genes, including BRCA2, ataxia telangiectasia mutated (ATM), mutL homolog 1 (MLH1), BRCA1 interacting protein C-terminal helicase 1 (BRIP1), partner and localizer of BRCA2 (PALB2), and fibroblast growth factor receptor 3 (FGFR3). Likely pathogenic missense variants were identified in checkpoint kinase 2 (CHEK2) and homeobox protein Hox-B13 (HOXB13). In total, 11 of 102 patients (10.8%) were found to have pathogenic or likely pathogenic mutations in cancer-predisposing genes. The majority of these men (64%) did not meet current clinical criteria for germline testing. CONCLUSIONS Men with prostate cancer and at least 1 additional primary cancer are enriched for harboring a germline deleterious mutation in a cancer-predisposing gene that may impact cancer prognosis and treatment, but the majority do not meet current criteria for clinical genetic testing. Cancer 2017. © 2017 American Cancer Society.
The Quiet Costs of Taxation: Cash Taxes and Noncash Bases

Tax law gives relief to “illiquid” taxpayers, those with income or wealth but no cash. This relief results in revenue losses, creates opportunities for tax avoidance, and distorts economic decisions. And yet, we don’t know how much hardship is actually created by illiquidity. This Article provides a framework for determining the magnitude of that hardship. The framework reveals that the costs of selling property or borrowing money to pay taxes in cash are not the only costs borne by illiquid taxpayers; they may also have to make painful adjustments in their current consumption or retirement savings plans. These are the “quiet” costs of taxation. I show that illiquidity hardship can be quantified in dollar terms and thereby placed on the same scale as other considerations that go into the evaluation of tax law and policy, allowing it to be weighed in the balance and making it possible to identify the contexts in which it truly matters. I demonstrate that illiquidity hardship is a meaningful concern in the property tax context but is a weak justification for the “realization” requirement under federal income tax law.
A History of Military Computer Simulation

The history of military simulation dates back to the earliest ages of conflict. Throughout the history, military personnel has employed cognitive devices to comprehend and plan for conflict. This chapter provides a history of military simulation, starting with a review of the board-based war games , progressing through the computerization of those war games and completing with a discussion of the modern world of military simulation encompassing desktop-based analytical simulations, video games, and distributed training and analytical environments. It provides a background for the contributions of the military track that has been a pillar of the Winter Simulation Conference for many years.
Novel pericatheter retrograde urethrogram technique is a viable method for postoperative urethroplasty imaging

The purpose of this study is to describe our technique for pericatheter retrograde urethrogram (pcRUG) and to evaluate the utility of a pcRUG to detect a clinically significant leak after urethral reconstruction. We retrospectively reviewed our prospective IRB-approved database of patients undergoing urethral reconstruction. pcRUG was performed at 3–4 weeks after surgery, in standardized fashion. Patients were placed in oblique position, and with the penis stretched, diluted contrast was instilled via an angiocatheter alongside the indwelling urethral catheter under dynamic fluoroscopy. The image was then evaluated for the presence of any contrast extravasation. Patient with and without extravasation seen on initial pcRUG were compared. From September 2012 through February 2017, 144 pericatheter retrograde urethrograms were performed on 130 patients. 115 patients (88.5%) had no extravasation on pcRUG. Fifteen patients (11.5%) demonstrated extravasation, with 13 of those patients (10%) undergoing a repeat pcRUG. Patients with extravasation seen on initial pcRUG were more likely to have strictures that were panurethral (36 vs. 9%, p = 0.029) and ≥10 cm (43 vs. 11%, p = 0.016). One patient (0.8%) presented with urinary leak and scrotal abscess after a urethra was assessed as sufficiently healed at the initial pcRUG and the catheter removed. There were otherwise no infectious or procedural complications related to pericatheter retrograde urethrogram. Our pericatheter retrograde urethrogram technique is a safe and reproducible technique to effectively assess urethral healing after urethroplasty and determine timing of catheter removal. The pcRUG is minimally invasive and is comparable in accuracy and sensitivity to voiding cystourethrography and retrograde urethrography that have traditionally been used to assess healing after urethroplasty.
Inter- and intra-subject variability of nitric oxide levels in leukocyte subpopulations

Assessment of nitric oxide (NO) dynamics in immune cells, commonly measured using NO surrogates such as inducible nitric oxide synthase (iNOS) rather than NO itself, has been effective in understanding pathophysiology across a wide range of diseases. Although the intracellular measurement of NO is now feasible, many technical issues remain unresolved. The principle aim of our study was to determine the effect of storage time of whole blood on nitric oxide (NO) level expression in leukocytes. This is important because immune cells remain chemically dynamic even after they are removed from the circulation, and the impact of storage time must be known to optimally quantify the effect of a disease or condition on NO dynamics in circulating leukocytes. We measured NO levels using the fluorescent probe, diaminofluorescein (DAF-2DA), and flow cytometry in monocytes, neutrophils, and natural killer cells from healthy subjects immediately after blood draw (Time 0) and 30, 60, and 120 min following the blood draw. There was no significant difference among the 4 study time points in NO (DAF-2) levels, though there was wide intra-subject variability at all time points. Using LPS stimulation, we compared iNOS (the more traditional surrogate marker of NO dynamics) with NO (by DAF-2) in natural killer cells and monocytes and, we found no difference in the response patterns. In summary, we did find that within a 2-hour interval from blood draw to sample processing, there was a remarkably wide intra-subject variability in expression of intracellular NO (DAF-2) in leukocytes of healthy individuals at baseline and over time. The mechanism(s) for these differences are not known but could clearly confound efforts to detect changes in NO metabolism in white blood cells. We speculate that rapid pulsatility of NO could explain the wide variability seen.
Multimodality optical coherence tomography and fluorescence confocal scanning laser ophthalmoscopy for image-guided feedback of intraocular injections in mouse models

Rodent models are robust tools for understanding human retinal disease and function because of their similarities with human physiology and anatomy and availability of genetic mutants. Optical coherence tomography (OCT) has been well-established for ophthalmic imaging in rodents and enables depth-resolved visualization of structures and image-based surrogate biomarkers of disease. Similarly, fluorescence confocal scanning laser ophthalmoscopy (cSLO) has demonstrated utility for imaging endogenous and exogenous fluorescence and scattering contrast in the mouse retina. Complementary volumetric scattering and en face fluorescence contrast from OCT and cSLO, respectively, enables cellular-resolution longitudinal imaging of changes in ophthalmic structure and function. We present a non-contact multimodal OCT+cSLO small animal imaging system with extended working distance to the pupil, which enables imaging during and after intraocular injection. While injections are routinely performed in mice to develop novel models of ophthalmic diseases and screen novel therapeutics, the location and volume delivered is not precisely controlled and difficult to reproduce. Animals were imaged using a custom-built OCT engine and scan-head combined with a modified commercial cSLO scan-head. Post-injection imaging showed structural changes associated with retinal puncture, including the injection track, a retinal elevation, and detachment of the posterior hyaloid. When combined with imagesegmentation, we believe OCT can be used to precisely identify injection locations and quantify injection volumes. Fluorescence cSLO can provide complementary contrast for either fluorescently labeled compounds or transgenic cells for improved specificity. Our non-contact OCT+cSLO system is uniquely-suited for concurrent imaging with intraocular injections, which may be used for real-time image-guided injections.
Early employment careers of people with disabilities in the National Child Development Study.

OBJECTIVES To compare the early employment careers of people with disabilities and their non-disabled contemporaries. STUDY DESIGN The employment of 436 people with disabilities was investigated between the ages of 23 and 33. The sample were part of a continuing longitudinal study, the National Child Development Study (NCDS), of some 17,000 people born during one week in 1958 and living in England, Wales and Scotland. Cross-tabulations were carried out comparing the employment of people with disabilities and that of their non-disabled counterparts using SPSS for Windows. RESULTS Despite the majority of the sample not having difficulties with everyday activities people with disabilities were disadvantaged in terms of educational and vocational qualifications, employment rates and earnings. Those with physical disabilities fared better than the other disability groups in terms of employment and earnings, among this group men with 'below average' educational and vocational qualifications differing most from their non-disabled counterparts and women with 'above average' qualifications differing least. CONCLUSIONS Findings indicate the importance of educational and vocational qualifications for those with disabilities, for more emphasis on job retention, for measures against wage discrimination, and for job placement assistance for some groups of those with a disability.
Validity and the Basic Norm

As we move towards the last quarter of the 20th century, there can no longer be any doubt that the formative jurist of our time is Hans Kelsen. If the mark of the genius is that he creates a cosmos out of chaos, then Kelsen has evidently earned that title. His pure theory of law has displayed for us, with splendid accuracy and elegance, the anatomy of a legal system. He has demonstrated the essential unity of law, the distinctive marks that separate the concept of law from that of morality, and the relationship between the legal order and the concept of the state. He has corrected the monocular excesses both of Austin, who placed exaggerated emphasis on the role of a sovereign commander, and of the American realists, with their obsessive concentration on judicial activity. No general writer on the concept of law in the last half-century has been able to ignore Kelsen, and there is no important contribution to the general philosophy of law in that period that does not owe much to Kelsen's work.
Improvements in RFID Physical Layer Using Ultra-wideband Signals

Even though narrowband RFID systems are currently quite mature and effective in many applications, the limitations posed by narrowband signal characteristics (discussed in Chap. 2) makes them somewhat unreliable for use in certain practical environments [1].
Genomics and Systems Biology

Abstract The Biological systems are complex, especially on a genomic scale. Individual genes interact and regulate one another to form a gene regulatory network that modulates genomic functions. Any aberrant activities disrupting the system can potentially lead to abnormal phenotypes such as human disorders. To systematically decode the biological complexity, advanced signal processing and network science approaches have been applied to model and analyze gene regulatory networks. In this chapter, we will review recent applications of signal processing and network-based methods to systems biology especially in the field of gene regulation. First, we will introduce genomic signal processing approaches that process and analyze the large-scale, next-generation sequencing data in the context of gene expression and regulatory activity analysis. Second, we will review the computational approaches for constructing and predicting gene regulatory networks including both directed and undirected graphs. Finally, we will summarize the network-based approaches for analyzing and modeling network topological structures such as gene clusters, motifs, hierarchies, and critical pathways. We will also discuss future directions on gene regulatory networks.
Refractive index of lithium fluoride to 900 gigapascal and implications for dynamic equation of state measurements

Lithium fluoride (LiF) is a unique crystal possessing the largest reported bandgap of any material and is predicted to remain transparent to visible light under stresses in excess of 1000 GPa. Dynamic compression experiments often utilize LiF as a window material to maintain stress on a sample while enabling direct measurements of interface velocity. However, typical velocimetry diagnostics measure changes in the optical path length; therefore, an accurate understanding of LiF’s equation of state and refractive index is needed. Here, we present a measurement of the LiF refractive index up to 900 GPa from a low-temperature ramp-compression experiment at the National Ignition Facility. To demonstrate propagation of optical uncertainty from this work to equation of state measurements, simulations in which a tin–LiF interface reaches a peak stress of 825 GPa show that the principal isentrope of tin can be determined up to 1450 GPa with a 1.2% uncertainty in density while considering uncertainties in the optical response of LiF.
Journalistic Autonomy in Voice of America’s Amharic Service: Actors, Deterrents, and Safeguards

Established in 1982, the Voice of America (VOA) Amharic Service became one of the most popular news outlets for Ethiopians in Ethiopia and Ethiopian diaspora communities across the world. Angered b...
Relationship between the Financial Indicators and the Implementation of Telework

In most European countries, teleworking or homeworking is used in various forms that differ from one another by its legal regulation. The paper examines the SME's in the Czech Republic from the perspective what makes them to adopt telework using the financial indicators. We hypothesized that employer adoption of telework would depend on some economic factors. The empirical evidence showed that a typical company that uses telework is a company with higher ratio of liabilities and therefore lower ratio of equity, a lower ratio of fixed assets, higher sales, lower inventory, higher labour productivity and higher value added per employee, higher return on equity, higher personnel costs, higher average wages. Within the analysed enterprises, 16 indicators were assessed; the 9 indicators showed the difference between companies that use telework and companies that do not use telework. The research shows a typical company that uses telework.
Artificial Intelligence: Practical Primer for Clinical Research in Cardiovascular Disease.

Artificial intelligence (AI) has begun to permeate and reform the field of medicine and cardiovascular medicine. Impacting about 100 million patients in the United States, the burden of cardiovascular disease is felt in a diverse array of demographics.1, 2 Meanwhile, routine mediums such as multimodality images, electronic health records (EHR), and mobile health devices store troves of underutilized data for each patient. AI has the potential to improve and influence the status quo, with capacity to learn from these massive data and apply knowledge from them to distinct circumstances.3, 4 With considerable information in each heart beat, cardiovascular medicine will definitely be one of the fields that embrace AI to move toward personalized and precise care.5 AI has already been woven into the fabric of everyday life. From an internet search engine, email spam and malware filtering, to uncovering fraudulent credit card purchases, AI addresses an individual's needs in the realms of business, entertainment, and technology. Unfortunately, medicine, including cardiology, has not fully embraced this revolution, with only a limited number of AI‐based clinical applications being available. Nevertheless, there is promise towards routine implementation; machine learning and deep learning have seen an exponential surge of cardiovascular publications in the past decade.6, 7 These methods have proven beneficial in a variety of complex areas including echocardiogram interpretation and diastolic dysfunction grade stratification.8, 9 The US Food and Drug Administration has already approved several devices that utilize AI features.10 Imagine coming to work finding that your system has analyzed all your patients while you were sleeping: their laboratory data, imaging results, symptoms, and mobile device data to calculate their risk of cardiovascular events, death, hospitalization, whether medications should be adjusted/added/removed, or whether they should be referred for an examination. The system presents you with the reasons for its recommendations, and you are confident that they are as good as those given by the most experienced physicians. This may allow you to spend time in shared decision making with your patients, both objectively and compassionately. Although there are currently several barriers/challenges to adoption of AI in clinical practice, undoubtedly, AI will drive current healthcare practice towards a more individualized and precision‐based approach over the next several years. Therefore, general understanding of AI techniques by clinicians and researchers in cardiovascular medicine is paramount. In this review article, we describe the fundamentals of AI that clinicians and researchers should understand, its definition and principles, how to interpret and apply AI in cardiovascular research, limitations, and future perspectives.
NITRIFICATION AND OTHER FACTORS AFFECTING NITROGEN IN THE HOLSTON RIVER

Many of the factors that affect nitrogen balance in free-flowing streams and impoundments are elucidated in light of recent literature. For free-flowing streams, emphasis is placed on evaluation of nitrification, denitrification and other reduction processes that affect nitrate nitrogen, and absorption and assimilation of nitrate and ammonium by aquatic plants. An analysis of nitrification and denitrification in the complex Holston River environment is then presented. The effects of nitrates, nitrites, organic nitrogen, and ammonium on eutrophication of reservoirs is then elucidated, and the effect of nitrogen on dissolved oxygen concentration on Cherokee Reservoir is discussed. Also, the effect of nitrogen on the Cherokee Reservoir fishery is discussed.
Complex magnetic phases enriched by charge density waves in the topological semimetals GdSb x Te 2 − x − δ

The interplay of crystal symmetry, magnetism, band topology, and electronic correlation can be the origin of quantum phase transitions in condensed matter. Particularly, square-lattice materials have been serving as a versatile platform to study the rich phenomena resulting from that interplay. In this work we report a detailed magnetic study on the square-lattice-based magnetic topological semimetal ${\mathrm{GdSb}}_{x}{\mathrm{Te}}_{2\ensuremath{-}x\ensuremath{-}\ensuremath{\delta}}$. We report the H-T magnetic phase diagrams along three crystallographic orientations and show that, for those materials where a charge density wave distortion is known to exist, many different magnetic phases are identified. In addition, the data hints towards the existence of an antiferromagnetic skyrmion phase, which has been theoretically predicted but not experimentally confirmed in a bulk material yet.
Next Steps: Sequencing Therapies in Metastatic Kidney Cancer in the Contemporary Era

Systemic therapy for first-line metastatic renal cell carcinoma has evolved toward immune checkpoint blockade combinations incorporating a PD-1/L1 inhibitor along with CTLA-4 inhibition or VEGF-targeted therapy. The new treatment paradigm that integrates immunotherapy for treatment-naive advanced metastatic renal cell carcinoma creates a new therapeutic challenge for clinicians including the optimal way to integrate multidisciplinary care involving surgery, radiotherapy, and application of contemporaneous systemic treatment in subsequent lines of therapy following discontinuation of combination therapy. We outline the available data for the multidisciplinary management of metastatic renal cell carcinoma, systemic therapy options in the post-immune checkpoint blockade setting, and novel therapies in development for advanced renal cell carcinoma. We provide practical considerations to assist clinicians in treatment choice and map future directions for progress.
Drug Alert Experience and Salience during Medical Residency at Two Healthcare Institutions.

Background Drug alerts are clinical decision support tools intended to prevent medication misadministration. In teaching hospitals, residents encounter the majority of the drug alerts while learning under variable workloads and responsibilities that may have an impact on drug-alert response rates. Objectives This study was aimed to explore drug-alert experience and salience among postgraduate year 1 (PGY-1), postgraduate year 2 (PGY-2), and postgraduate year 3 (PGY-3) internal medicine resident physicians at two different institutions. Methods Drug-alert information was queried from the electronic health record (EHR) for 47 internal medicine residents at the University of Pennsylvania Medical Center (UPMC) Pinnacle in Pennsylvania, and 79 internal medicine residents at the MetroHealth System (MHS) in Ohio from December 2018 through February 2019. Salience was defined as the percentage of drug alerts resulting in removal or modification of the triggering order. Comparisons were made across institutions, residency training year, and alert burden. Results A total of 126 residents were exposed to 52,624 alerts over a 3-month period. UPMC Pinnacle had 15,574 alerts with 47 residents and MHS had 37,050 alerts with 79 residents. At MHS, salience was 8.6% which was lower than UPMC Pinnacle with 15%. The relatively lower salience (42% lower) at MHS corresponded to a greater number of alerts-per-resident (41% higher) compared with UPMC Pinnacle. Overall, salience was 11.6% for PGY-1, 10.5% for PGY-2, and 8.9% for PGY-3 residents. Conclusion Our results are suggestive of long-term drug-alert desensitization during progressive residency training. A higher number of alerts-per-resident correlating with a lower salience suggests alert fatigue; however, other factors should also be considered including differences in workload and culture.
Precision metrology system for the Hubble Space Telescope Wide Field Camera 3 instrument

The Wide Field Camera 3 (WFC3) instrument for the Hubble Space Telescope (HST) will replace the current Wide Field and Planetary Camera 2 (WFPC2). By providing higher throughput and sensitivity than WFPC2, and operating from the near-IR to the near-UV, WFC3 will once again bring the performance of HST above that from ground-based observatories. Crucial to the integration of the WFC3 optical bench is a pair of 2-axis cathetometers used to view targets which cannot be seen by other means when the bench is loaded into its enclosure. The setup and calibration of these cathetometers is described, along with results from a comparison of the cathetometer system with other metrology techniques.
Internet search trends in refractive diseases and interventions during the COVID-19 pandemic

Purpose : To assess national and international internet search trends and public interest in refractive diseases and interventions during the COVID-19 pandemic compared to existing trends prior to the pandemic. Methods : A Google Trends search for refractive terms was performed between the time periods of January 1, 2016 to November 1, 2020. Refractive terms were divided into two groups: disease terms and procedure/treatment terms. Relative search volume (RSV) indices for refractive terms were assessed in the United States (US) and worldwide from the initial 18-week COVID-19 pandemic period (March 1, 2020 to July 4, 2020) and the subsequent 18-week period. (July 5, 2020 to November 1, 2020) These results were compared to pooled data of overlapping weeks between 2016-2019. A t-test of two independent samples assuming unequal variances was utilized to compare the two groups. Results : The relative public interest in refractive disease and procedure/treatment terms showed a sharp decline in the initial 18-weeks of the pandemic with a slow increase over the following 18-weeks compared to prior to the pandemic (Figure 1). There was a statistically significant decrease in mean RSV for multiple refractive disease terms (near far sighted/sightedness, keratoconus, hyperopia, cataract, astigmatism, myopia, near sighted/sightedness, blurry/blurred vision) and refractive procedure/treatment terms (intraocular lens, LASIK, cataract surgery/removal/extraction, LASEK, contact lens/lenses) both in the US and worldwide in 2020 compared to 2016-2019. Conclusions : The onset of the COVID-19 pandemic correlates with declining relative popularity of searches related to refractive disease and elective refractive procedures/treatments. Declining interest in refractive diseases and treatments may lead to poorer health literacy, delay in care, and potentially worse outcomes for these conditions.
Effects of dietary aspirin on high-LET radiation-induced prostaglandin E2 levels and gastrointestinal tumorigenesis in Apc1638N/+ mice.

Abstract Inevitable exposure to high-LET ionizing radiation (IR) present in galactic cosmic radiation (GCR) could enhance gastrointestinal (GI) cancer incidence among astronauts undertaking deep space exploration and GI-cancer mortality has been predicted to far exceed NASA's limit of 2mm2), number, and cluster (>5 adjoining tumors) were analyzed at 150 days post-exposure. Aspirin led to a significant reduction in PGE2 in a dose-dependent manner but did not reduce 28Si-induced GI tumorigenesis even at the highest (300 mg/day) dose. In summary, this study suggests that aspirin could reduce high-LET IR-induced pro-inflammatory PGE2 levels, however, lacks the ability to reduce high-LET IR-induced GI tumorigenesis in Apc1638N/+ mice.
Alpha 2-Adrenergic Receptor Modulation of Calcium Current is Impaired in Mesenteric Artery Projecting Sympathetic Neurons in DOCA-Salt Hypertensive Rats

In sympathetic neurons, activation of the prejunctional alpha 2-adrenergic receptor (a2-AR) inhibits nerve terminal N-type Ca2+ channels and norepinephrine (NE) release onto blood vessels. In rats,...
Applying Fuzzy Hypothesis Testing to Medical Data

Classical statistics and many data mining methods rely on “statistical significance” as a sole criterion for evaluating alternative hypotheses. In this paper, we use a novel, fuzzy logic approach to perform hypothesis testing. The method involves four major steps: hypothesis formulation, data selection (sampling), hypothesis testing (data mining), and decision (results). In the hypothesis formulation step, a null hypothesis and set of alternative hypotheses are created using conjunctive antecedents and consequent functions. In the data selection step, a subset D of the set of all data in the database is chosen as a sample set. This sample should contain enough objects to be representative of the data to a certain degree of satisfaction. In the third step, the fuzzy implication is performed for the data in D for each hypothesis and the results are combined using some aggregation function. These results are used in the final step to determine if the null hypothesis should be accepted or rejected. The method is applied to a real-world data set of medical diagnoses. The automated perception approach is used for comparing the mapping functions of fuzzy hypotheses, tested on different age groups (“young” and “old”). The results are compared to the “crisp” hypothesis testing.
Amyotrophic lateral sclerosis onset is influenced by the burden of rare variants in known amyotrophic lateral sclerosis genes.

Objective To define the genetic landscape of amyotrophic lateral sclerosis (ALS) and assess the contribution of possible oligogenic inheritance, we aimed to comprehensively sequence 17 known ALS genes in 391 ALS patients from the United States. Methods Targeted pooled-sample sequencing was used to identify variants in 17 ALS genes. Fragment size analysis was used to define ATXN2 and C9ORF72 expansion sizes. Genotype–phenotype correlations were made with individual variants and total burden of variants. Rare variant associations for risk of ALS were investigated at both the single variant and gene level. Results A total of 64.3% of familial and 27.8% of sporadic subjects carried potentially pathogenic novel or rare coding variants identified by sequencing or an expanded repeat in C9ORF72 or ATXN2; 3.8% of subjects had variants in >1 ALS gene, and these individuals had disease onset 10 years earlier (p = 0.0046) than subjects with variants in a single gene. The number of potentially pathogenic coding variants did not influence disease duration or site of onset. Interpretation Rare and potentially pathogenic variants in known ALS genes are present in >25% of apparently sporadic and 64% of familial patients, significantly higher than previous reports using less comprehensive sequencing approaches. A significant number of subjects carried variants in >1 gene, which influenced the age of symptom onset and supports oligogenic inheritance as relevant to disease pathogenesis. ANN NEUROL 2015;77:100–113
Predictors of reoperation-free survival following decompression-alone lumbar spine surgery for on-the-job injuries.

Abstract Introduction Workers’ compensation patients are known to be associated with inferior outcomes following lumbar surgery. We investigated demographics and clinical characteristics between the reoperative and non-reoperative group of patients undergoing decompression-alone lumbar surgery (discectomy and/or laminectomy) for on-the-job injuries (OJI) at our institute, and evaluated its possible impact on the reoperation-free survival (RFS). Methods A retrospective analysis of patients undergoing lumbar surgery for OJI between 2003 through 2010 by a single surgeon (A.N.) was performed. A comparison of baseline clinical and demographic parameters between the two groups was compared using Fisher's exact test for the categorical variables and the independent t-test (2-tailed) for the continuous variables. Overall, RFS was presented in Kaplan–Meier curves and the RFS difference was compared using log-rank (Mantel–Cox) test. Cox proportional hazard model was used for the univariate and multivariate analysis and hazard ratios with 95% confidence intervals were reported. Results About 92 patients with mean age 48.07 ± 10.10 years and mean follow-up of 36.4 (range 24.3–66.0) months were included. About 38 (41.3%) patients underwent reoperation for failed decompression-alone procedures whereas the non-reoperative cohort comprises 54 (58.7%) patients. Female gender (p = 0.015) and history of previous surgery (p = 0.05) were associated with a higher chance of reoperation. Majority of the reoperations (20/38, 52.6%) were performed within the first 2 years, with a RFS at the end of 2 years being 78.3% (n = 72) and 58.9% (n = 53) at 5 years. Cox-regression analysis did not demonstrate any influence of patients and treatment-related factors on the RFS. Conclusion There is a substantial risk of redo surgeries following decompression-alone lumbar procedures for OJI. As patient and treatment-related factors did not influence the reoperation rates and RFS in this study, it appears that workman compensation status of patients is inherently associated with poor outcomes following spine surgeries.
Existence of Equilibria in Auctions with Interdependent Values: Two Symmetic Bidders

For two symmetric bidders, weak monotonicity conditions are shown to imply existence of an equilibrium in mixed behavioral strategies for a sealed-bid first-price auction of an item for which each bidder's value depends on every bidder's observed signal. Such an equilibrium has atomless distributions of bids and thus is unaffected by how tied bids are resolved.
Silicon measurements of characteristics for passgate/pull-down/pull-up MOSs and search MOS in a 28 nm HKMG TCAM bitcell

Test structures for measuring characteristics of MOS components in 28 nm high-k metal-gate (HKMG) Ternary Content-Addressable memory (TCAM) bitcell are implemented. Proposed TCAM bitcell are including pull-down (PD) and pass-gate (PG) NMOSs, pull-up (PU) PMOSs and search NMOSs, which are built up based on standard 6T SRAM bitcell. It can achieve the small area but symmetrical layout could not be implemented. Each MOS characteristic is measured by test structure and observed over 20 mV V t offset for each PD and PG NMOS pairs due to asymmetrical layout, whereas there is no difference in PU-PMOS pair. From measurement results we estimate the bit error rates on the supply voltage for TCAM array and predict that the TCAM V min for read-operation becomes worse by 42 mV at 5.3-sigma condition compared to that of standard SRAM array. Based on measured bitcell characteristics we designed and fabricated 80-Mbit TCAM test chips with appropriate redundancies, achieving below 740 mV V min at 250 MHz operation at 25°C and 85°C.
Trypsin inhibitor from bovine pancreatic juice.

Abstract A trypsin inhibitor has been isolated in 54% yield from bovine pancreatic juice by gel filtration on Sephadex G-75 at pH 8.1 and by elution chromatography on DEAE-cellulose at pH 9.0. It appears to be homogeneous by equilibrium chromatography, equilibrium sedimentation ultracentrifugation, and amino acid analysis, and on the basis of the stoichiometry of its interaction with trypsin. The polypeptide inhibitor has a molecular weight of 6155 and has the following amino acid composition: Asp7, Thr4, Ser2, Glu7, Pro4, Gly5, Ala1, Cys6, Val4, Met1, Ileu3, Leu4, Tyr2, Lys3, and Arg3. The inhibitor is secreted in the pancreatic juice in the free form (not in a complex with trypsin) and it prevents the trypsin-catalyzed activation of the proteolytic zymogens. The amount of inhibitor is equivalent to 1% of the total potential trypsin in pancreatic juice. Although two trypsin inhibitors have been isolated from acid extracts of the gland, only one (Kazal type) is present in the secretion. This suggests that the inhibitors are segregated at the subcellular level in the pancreatic acinar cells.
Astaxanthin Plays Anti-inflammatory and Antioxidant Effects by Inhibiting NFkB Nuclear Translocation and NOX2 Expression in Macrophages

Chronic inflammation and oxidative stress are associated with obesity-related metabolic diseases such as non-alcoholic fatty liver disease, type 2 diabetes, and cardiovascular disease. Astaxanthin (ASTX), a xanthophyll carotenoid, has been suggested to play anti-inflammatory and antioxidant functions. We investigated potential mechanisms of action by which ASTX exerts the anti-inflammatory and antioxidant effects in macrophages. When RAW 264.7 macrophages were stimulated by LPS (100 ng/ml) for 24 h, mRNA expression of IL-6 and IL-1β was increased. However, co-incubation with ASTX (25 mM) significantly attenuated the induction. ASTX markedly decreased LPS-induced nuclear translocation of nuclear factor kB (NFkB). In addition, LPS increased cellular reactive oxygen species (ROS), which was abolished by ASTX with a concomitant decrease in NADPH oxidase 2 (NOX2) expression. Bone marrow-derived macrophages (BMDM) isolated from wild-type and nuclear factor E2 related factor 2 (Nrf2) knockout mice were incubated...
Antenatal diagnosis and management of the small-for-gestational age fetus.

Abstract A new classification of small birth weight neonates (approximately 2,600 grams or less) has been developed. This classification is based on gestational age and birth weight determinations. With the use of physical, neurological, and electroencephalographic determinations, more accurate gestational age measurements can be made. From these measurements, fetal growth curves have been developed that present percentile distribution of birth weight at successive gestational periods. This report describes from an obstetric viewpoint the results of analysis of a group of 48 infants who were small for gestational ages.
Lithium abundance and surface magnetic fields: new constraints in magnetic models of M dwarfs

Precision modeling of M dwarfs has become worthwhile in recent years due to the increasingly precise values of masses and radii which can be obtained from eclipsing binary studies. Torres (2013) has identified 4 prime M dwarf pairs with the most precise empirical determinations of masses and radii. The measured radii are consistently larger than standard stellar models predict. We have previously modeled M dwarfs in the context of a criterion due to Gough & Tayler in which magnetic fields inhibit the onset of convection according to a physics-based prescription. New constraints on the models of M dwarfs are now provided by measurements of lithium abundances. The key aspect of Li in terms of setting constraints on magnetic modeling is that Li burning starts at T = 2.5 MK, and temperatures of just such magnitude are associated with the base of the convection zone: magnetic inhibition of convective onset can shift this base slightly closer to the surface, i.e. to slightly lower temperatures, thereby reducing the amount of Li depletion compared to a non-magnetic model. In the present paper, we consider how our magneto-convection models handle the new test of stellar structure provided by Li measurements. Among the prime systems listed by Torres, we find that plausible magnetic models work well for CM Dra and YY Gem but not for CU Cnc. (The fourth system in Torres's list does not yet have enough information to warrant magnetic modeling.) For CU Cnc, we suggest that the observed lithium may have been accreted from a circumstellar disk. We find that our magneto-convection models of CM Dra, YY Gem and CU Cnc yield results which are consistent with the observed correlation between magnetic flux and X-ray luminosity.
Characterization of early pulmonary hyperproliferation and tumor progression and their inhibition by black tea in a 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis model with A/J mice

Abstract The pathogenesis of pulmonary tumors induced by a tobacco carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and its inhibition by black tea have been characterized. Female A/J mice (6 weeks old) were treated with a single dose of NNK (103 mg/kg of body weight, i.p.) on day 0, and the cell proliferation index was measured by the incorporation of bromodeoxyuridine (BrdUrd) immunohistochemically. The number of BrdUrd-labeled cells increased in the bronchiolar epithelium from day 2 to day 14, with the highest proliferation rate observed on day 5. By day 35, the BrdUrd-labeling index returned to the level of the control group. Further examination of the day 35 samples revealed the presence of foci of hyperproliferative cells in the bronchiolar epithelium, particularly in the bronchiolalveolar regions. These proliferating bronchiolar epithelial cells (Clara cells) may be the initiated sites for pulmonary tumorigenesis. In this short-term model, administration of black tea polyphenols (0.3%) through the drinking water starting 24 h after NNK treatment significantly inhibited NNK-induced early bronchiolar cell proliferation on day 5. In long-term studies, adenomas were observed in 100% (15 of 15) of the mice at week 16, with 7.8 ± 0.8 tumors per mouse. At week 52, a malignant tumor incidence of 80% (41 of 51 mice) and a malignant tumor multiplicity of 2.39 ± 0.19 were observed. The growth patterns of the malignant tumors, which included solid, papillary, and mixed types, may be associated with the cellular origin of the tumor. The cell proliferation indices, as measured by proliferating cell nuclear antigen immunohistochemistry, were significantly higher in dysplasia within adenoma than in adenoma, and significantly higher in adenoma at week 52 than in adenoma at week 16. Administration of black tea, starting 16 weeks after a single dose of NNK, inhibited the progression of adenoma to adenocarcinoma as determined by both malignant tumor incidence and multiplicity. The cell proliferation rate in adenomas was also suppressed by black tea treatment. The present work demonstrates the antiproliferative activities of black tea and its polyphenols. Such activities, at the early and late stages of lung tumorigenesis, may be important for the cancer-chemopreventive activities of black tea.
Validation of Numerically Simulated Tissue Temperatures During Transcutaneous Recharge of Neurostimulation Systems.

Objective A research study combining numerical simulation and animal-model experiments has been performed to assess the ability of simulation to accurately calculate temperatures within living tissue during the recharge of a neuromodulation system (Restore Ultra device, Medtronic Neuromodulation, Minneapolis, MN, USA). Materials and Methods The experiments were carried out on a sheep with the neuromodulation implant set to depths of 0.6 cm and 2.1 cm. Temperatures were recorded on the surfaces of the implant and on the sheep skin. Finite element simulations were carried out to determine the degree to which the simulations and experiments match. Additional calculations were performed for an intermediate implant depth. Results It was found that there was excellent agreement between the simulations and the animal model for both depths. Conclusion It is shown that numerical simulation using the Pennes bioheat equation is capable of predicting temperature increases within living tissues when implanted heat-generating devices are in use. The device used in the present study does not give rise to temperatures which cause concern of thermal injury or safety. The study was performed for aligned antenna and implant.
Penguin Contribution to the Phase of B_s-\bar B_s Mixing and B_s -> mu mu in Grand Unified Theories

Abstract We investigate the possibility of a large B s – B s ¯ mixing phase in the context of grand unified theory (GUT) models, e.g., SO(10) and SU(5). In these models, we find that a large phase of B s mixing is correlated with Br( b → s γ ), Br( τ → μ γ ) and Br( B s → μ μ ) for large tan β . In the case of the SO(10) model, the large phase of B s mixing is correlated with Br( b → s γ ) and Br( B s → μ μ ) and we find that a large B s mixing corresponds to an enhanced Br( B s → μ μ ) about to be probed by the Tevatron. In the case of the SU(5) model, the large phase is correlated with Br( τ → μ γ ) and Br( B s → μ μ ). In this case, the Br( τ → μ γ ) constraint requires a smaller pseudo-scalar Higgs mass which in turn generates a large Br( B s → μ μ ) almost at the edge of present experimental constraint. If the present observation of large phase of B s mixing persists in the upcoming data, using all these branching ratios, we will be able to distinguish these models.
A SPECTROPHOTOMETRIC METHOD FOR MEASURING SERUM TRYPSIN INHIBITOR CAPACITY.

The spectrophotometric method of Schwert and Takenaka (11) for the assay of trypsin esterolytic activity has been modified for the measurement of the trypsin inhibitor capacity of serum. An average value of 0.99 mg. of trypsin inhibited per milliliter of serum (3 S.D. = ±0.30) was determined for 50 control subjects. Patient serum assay values determined with this method have been found similar to those determined with the modified Kunitz method using l131-labeled casein as the substrate-in the normal range for a variety of pathologic conditions and in the elevated range for abnormalities of the pancreas and generalized cancer conditions. From the standpoints of accuracy, simplicity, and speed this technic is believed to be an improvement over previous methods for the measurement of this serum variable.
Potentiation of Clostridium botulinum Toxin by Aminoglycoside Antibiotics: Clinical and Laboratory Observations

A child with infant botulism became apneic and died while receiving ampicillin and gentamicin therapy. As aminoglycosides have been implicated in the induction and/or exacerbation of neuromuscular blockade, we used an animal model to test the hypothesis that aminoglycosides potentiate neuromuscular blockade of botulinum toxin. In the range of aminoglycoside doses utilized in these experiments, both gentamicin and tobramycin enhance neuromuscular impairment and death of botulinum toxin-exposed mice. These results support recently published clinical observations that aminoglycosides may potentiate neuromuscular weakness caused by botulinum toxin, and suggest that these antibiotics should be used with caution in suspected cases of infant botulism.
Computing True Shadow Prices in Linear Programming.

Abstract : It is well known that in linear programming, the optimal values of the dual variables can be interpreted as shadow prices (marginal values) of the right-hand-side coefficients. However, this is true only under nondegeneracy assumptions. Since real problems are often degenerate, the output from conventional LP software regarding such marginal information can be misleading. This paper surveys and generalizes known results in this topic and demonstrates how true shadow prices can be computed with or without modification to existing software. Keywords: Optimization software.
A 10 GS/s Distributed Waveform Generator for Sub-Nanosecond Pulse Generation and Modulation in 0.18μm Standard Digital CMOS

A distributed waveform generator is presented for sub-nanosecond pulse generation in UWB impulse radios. It time-interleaves multiple digital pulse generators, and uses an on-chip transmission line for wideband pulse combining. Compared to other UWB pulse generation and shaping solutions, it is low power and fully reconfigurable. A 10-tap, 10 GS/s prototype was implemented in 0.18μm standard digital CMOS. It consumes 50 mW at 1 GHz pulse repetition rate. On-off keying modulation is demonstrated using 16 Mb/s PRBS data.