cssi/SciSciGPT-SciSciNet huggingface dataset:
A fixed-dose combination of ledipasvir and sofosbuvir ± ribavirin for treatment of hepatitis C infection: a systematic review and meta-analysis

Novel antivirals have shown promising results in the treatment of hepatitis C. Our objective was to perform a meta-analysis of the efficacy and safety of a fixed-dose combination (FDC) of ledipasvir + sofosbuvir and compare outcomes with the addition of ribavirin (RBV) to treatment with the FDC. We searched PubMed, EMBASE, and Cochrane CENTRAL from inception through to 9 February 2017. We used a random effects model to calculate untransformed proportions (PRs) and pooled odds ratios (ORs) with 95% confidence intervals (CIs) to compare outcome measures [sustained virologic response at 12 weeks after treatment completion (SVR12); any, serious, and individual adverse events] between groups receiving the FDC ± RBV. We performed the systematic review according to PRISMA guidelines. A total of 21 studies with 3826 patients were included in the meta-analysis. Ledipasvir/sofosbuvir was effective in achieving SVR12 after 8 weeks of therapy in genotype (GT) 1 treatment-naive patients without cirrhosis (PR 0.941; 95% CI 0.910–0.971; p < 0.001; I 2 = 0%). Similarly, it was effective after 12 weeks of therapy in GT1a and 1b patients irrespective of baseline viral load, presence of cirrhosis and CC interleukin-28B (IL28B) GT status. The SVR12 results after 12 weeks of therapy in GT1 patients were similar in groups ± RBV [PR 0.968 (95% CI 0.952–0.985), p < 0.001, I 2 = 46%, and PR 0.973 (95% CI 0.958–0.988), p < 0.001, I 2 = 64%, respectively]. Meta-analysis of comparative studies showed no benefit of adding RBV to ledipasvir/sofosbuvir in achieving SVR12 after 12 weeks of treatment in GT1 patients [OR 1.44 (95% CI 0.34–6.07); p = 0.62; I 2 = 57%], irrespective of cirrhosis. Twelve weeks of ledipasvir/sofosbuvir is effective in the treatment of GT1a and 1b patients, including those with cirrhosis and difficult to treat non-CC IL28B GTs, and addition of RBV does not confer any benefit in these patients. Eight weeks of ledipasvir/sofosbuvir therapy alone may be sufficient in treatment-naive GT1 patients without cirrhosis.
Market share growth and stock returns

We find a negative relationship between market share growth and subsequent stock returns, three- and four-factor alphas. We report the potential explanatory role of market share growth in explaining subsequent average monthly stock returns. High (Low) market share growth firms report good (poor) operating performance and positive (negative) SUEs in the quarter in which market share growth is measured and investors overact to that good (bad) news. However, high (low) market share growth firms experience decrease (increase) in operating performance and SUEs in the subsequent quarters resulting in corrections in investors’ expectations and subsequent lower (higher) stock returns.
A recovery coefficient study using pre-clinical hollow spheres in clinical PET/CT scanners

Aim: To measure and study the recovery coefficients of pre-clinical hollow spheres in clinical PET/CT scanners. Materials and Methods: Seven small hollow spheres with inner diameters ranging from 3.95mm up to 15.43mm, were imaged in a Jaszczak ECT Phantom, in air and with sphere to background activity concentration ratios of 15 to 1 for 16 minutes. The images were reconstructed to 2×2×2 mm voxel size images using the default clinical reconstruction method supplied by the scanner. The imaging protocol was performed on five different PET/CT scanners; the Gemini TF and Vereos by Philips, the mCT and HRRT by Siemens, and the Discovery 710 by General Electric. Results: The NEMA NU2 recovery coefficient for the 15.43 mm and 12.43 mm diameter spheres were about the same within each scanner. The Philips Vereos and HRRT scanners had RC values of 108% and 104% respectively, while the GE Discovery 710 was 118% and the Siemens mCT was 126%. The Gemini TF was 76%. For the smallest hollow sphere of 3.95 mm, the RC were 6.6%, 3.6%, 13%, 8.9% and 6.1% for the Gemini TF, Vereos, Discovery 710, mCT and HRRT respectively. An anomalous increase in the RC for the Discovery 710 and mCT was found for sphere sizes 9.89 mm diameter spheres where the RC was 161% and 145% for each respectively. A related recovery coefficient parameter called RC I which measures the recovery coefficient of the integrated activity in the spheres did not show this anomaly of increased recovery above 100% at the 9.89 mm sphere diameter measurement. Conclusion: The recovery coefficient data resulting from scanning five different scanners is presented. An increase in the recovery coefficient is seen in two scanners which is possibly due to over correction by the iterative reconstruction used to generate the images. This effect is not present when measuring the total activity in the sphere.
“questing toward what might otherwise be:” Adrienne Rich’s Later Work

(2017). “questing toward what might otherwise be:” Adrienne Rich’s Later Work. Women's Studies: Vol. 46, Adrienne Rich, pp. 704-717.
The Role of Alkoxide Initiator, Spin State, and Oxidation State in Ring-Opening Polymerization of ε-Caprolactone Catalyzed by Iron Bis(imino)pyridine Complexes.

Density functional theory (DFT) is employed to characterize in detail the mechanism for the ring-opening polymerization (ROP) of e-caprolactone catalyzed by iron alkoxide complexes bearing redox-active bis(imino)pyridine ligands. The combination of iron with the non-innocent bis(imino)pyridine ligand permits comparison of catalytic activity as a function of oxidation state (and overall spin state). The reactivities of aryl oxide versus alkoxide initiators for the ROP of e-caprolactone are also examined. An experimental test of a computational prediction reveals an Fe(III) bis(imino)pyridine bis-neopentoxide complex to be competent for ROP of e-caprolactone.
How reviewers’ use of profanity affects perceived usefulness of online reviews

This research explores the effects of profanity on perceptions of online reviews’ usefulness. Based on the prior research that described asymmetric attribution effects, we predict that when consumers see profanity in an online review, their reactions differ depending on the valence of the review. Specifically, when profanity is used in a negative review, it should reduce review usefulness because of decreased perceived reviewer objectivity. Among positive reviews, profanity increases review usefulness through greater perceived reviewer credibility. Through analysis of Yelp data, we show that the effect of profanity on usefulness depends on review valence. Experimentally, we demonstrate the opposing mediating effects of perceived objectivity and credibility on the usefulness of the review.
Mono(ADP-Ribosyl)transferases and Their Effects on Cellular Metabolism

Publisher Summary This chapter discusses the inhibition of protein synthesis and activation of adenylate cyclase. Diphtheria toxin and Pseudomonas exotoxin A inhibit protein synthesis in susceptible cells and in cell-free systems by catalyzing the ADP-ribosylation of a single amino acid in elongation factor II (EF-II), which then becomes inactive in protein synthesis. These toxins apparently do not ADP-ribosylate other proteins, presumably because they lack the post-translationally modified histidine that serves as the ADP-ribose acceptor in EF-II. Choleragen has been a valuable tool in the work that has resulted in the isolation and characterization of the guanyl nucleotide-binding component (G/F) of the cyclase. In addition, demonstration of the enzymic activity of choleragen leads directly to the question whether animal cells employ ADP-ribosylation in a controlled way to regulate adenylate cyclase activity.
Acoustic Image Models for Obstacle Avoidance with Forward-Looking Sonar

Long-range forward-looking sonars (FLS) have recently been deployed in autonomous unmanned vehicles (AUV). We present models for various features in acoustic images, with the goal of using this sensor for altitude maintenance, obstacle detection and obstacle avoidance. First, we model the backscatter and FLS noise as pixel-based, spatially-varying intensity distributions. Experiments show that these models predict noise with an accuracy of over 98%. Next, the presence of acoustic noise from two other sources including a modem is reliably detected with a template-based filter and a threshold learned from training data. Lastly, the ocean floor location and orientation is estimated with a gradient-descent method using a site-independent template, yielding sufficiently accurate results in 95% of the frames. Temporal information is expected to further improve the performance.
Identifying Major Sedimentary Basins Beneath the West Antarctic Ice Sheet from Aeromagnetic Data Analysis

In the Ross Sea, large sedimentary basins reflect primarily the major extensional event associated with the Late Cretaceous breakup of Gondwana. Within the Interior Ross Embayment, no similar large basins have been identified to date. We have used aerogravity and Werner deconvolution methods applied to aeromagnetic data to map depth to magnetic basement, which helped delineate three major sedimentary basins, the Bentley Subglacial, Onset, and Trunk D Basins.
A High Pressure Study of Ortho-para Conversion in Hydrogen by NMR

We have developed a system for studying NMR in a diamond anvil cell (DAC) resulting in an increased sensitivity of a few orders of magnitude. The DAC was loaded with solid hydrogen and studied to a pressure of 12.8 GPa in the temperature range of 4.2 to 77.3 K. We measured free induction decays and spin echoes. From this we could determine the ortho-para conversion rate. Conversion measurements were made at both low and high temperatures and are possible because at high pressure the sample remains solid. The rate constant rises to 58 %/hr at our highest pressure.
Writing Clinical Research Protocols: Ethical Considerations

Writing Clinical Research Protocols: Ethical Considerations by Evan DeRenzo, Joel Moss Elsevier Academic Press, 2006 ISBN 0-122-10751-9 Paperback: 320 pp, $39.95 1. Carol McCoy, PhD MT(ASCP)CLS 1. Director. Clinical Laboratory Science Program, Fairview Health Services, 2450 Riverside Avenue W1-505, Minneapolis MN 55454 Writing Clinical Research Protocols was written for the novice as well as the experienced clinical researcher. Authors Drs. Evan DeRenzo and Joel Moss divided the book into four sections: The Basics; Preparing the Protocol; Procedures, Methods, Statistics, Data Management, and Record Keeping; and Special Issues. In all aspects of the book, the theme that emerges involves the ethical issues to be considered when undertaking clinical research. In the section entitled The Basics, the authors provide background information as well as the history of clinical research. They present the regulatory issues that apply to clinical research and tie it back to historical happenings. As is often the case, abuse led to regulations. Preparing the Protocol focuses on the research subject. These chapters stress the importance of evaluating the risk and benefits of the study as well as the selection of the subject. To illustrate their points, the authors tie in excellent examples. Certainly for the novice clinical researcher this section is a must-read. As a clinical laboratory scientist, Preparing the Protocol was interesting but did not present information applicable to our role in clinical research as it exists today. However, with the potential broadening of the field to encompass clinical research, this section could provide pertinent background information. The section on Procedures, Methods, Statistics, Data Management, and Record Keeping fills fewer than 30 pages. Ethically, clinical research can not follow experimental research format. A mixture of qualitative and quantitative research methods are discussed, with a heavier emphasis on the qualitative. The…
Psychotherapy for PTSD and stress disorders

Abstract LMIC are affected by serious issues that contribute to the development of traumatic stress, such as war and conflict, internal displacement, poverty, food insecurity, and disease. Evidence-based psychological treatments for PTSD have been developed and tested in high-income countries, but less research has been conducted in LMIC to examine if similar treatments for PTSD are efficacious in various cultural contexts and within a range of delivery settings. In this chapter, we review psychological interventions for PTSD and stress disorders that have been evaluated in LMIC, provide an overview of their efficacy, synthesize the strengths and weaknesses of empirical work to date, and discuss future directions for research and treatment implementation. Resulting studies were organized by population stressor into the following sections: ( American Psychiatric Association, 2013 ) conflict and violence, ( Scott, Koenen, Aguilar-Gaxiola, et al., 2013 ) natural disasters, and ( Turner & Lloyd, 1995 ) gender-based violence, including comorbid medical conditions. Existing interventions have several methodological strengths, such as numerous studies utilizing empirically supported approaches, group-based intervention structures, and delivery by nonspecialists in mental health (e.g., lay counselors or community health workers). The treatments evaluated are on a continuum of traditions from those in the CBT framework such as TF-CBT and NET to broader psychological treatments such as problem-solving, IPT, and BA. A limitation is that trials have largely compared treatments with a wait list control, no-treatment control, or treatment-as-usual condition. Therefore, for many PTSD trials, the extent of the effect attributable to treatment is not clear. Future directions should include testing mechanisms of change in treatment, developing brief and scalable interventions that have been culturally tailored, and using attention-matched control comparisons to elucidate effective treatment components.
Acute exposure to 4-OH-A, not PCB1254, alters brain aromatase activity but does not adversely affect growth in zebrafish.

Abstract Acute developmental exposure to pharmaceuticals or environmental contaminants can have deleterious, long lasting effects. Many of these compounds are endocrine disruptors (EDCs) that target estrogen signaling, with effects on reproductive and non-reproductive tissues. We recently reported that zebrafish larvae transiently exposed to the pharmaceutical EDC 4-OH-A display visual deficits as adults. Here, we examine whether these long-term effects are due to compound-induced morphological and/or cellular changes. Zebrafish aged 24 h, 48 h, 72 h, or 7 days post-fertilization (larvae) or 3-4mos (adults) were exposed to either 4-OH-A or PCB1254 for 24 h. After that time, notochord length, eye diameter, inter-eye distance, and heart rate were measured from larvae; and aromatase (estrogen synthase) activity was measured in homogenates of adult brain tissue. In general, indices of larval growth and development were not altered by 24 h exposure to either compound. 4-OH-A potently inhibited aromatase activity, while PCB1254 did not, with inhibition continuing even after removal from treatment. These results support differential function of EDCs and indicate that developmental exposure to 4-OH-A causes sustained inhibition of aromatase, which could be associated with altered adult behaviors.
Iridocorneal Endothelial Syndrome with Contralateral Guttate Endothelial Dystrophy: A Light and Electron Microscopic Study

Abstract Both eyes from a 75-year-old woman who had unilateral closedangle glaucoma, characteristic endothelial specular microscopic findings, and slowly progressive tractional iris abnormalities consistent with essential iris atrophy were obtained postmortem and studied by light, scanning, and transmission electron microscopy. Clinically, the nonglaucomatous right eye had an open-angle, normal iris, and severe endothelial dystrophy with three-plus corneal guttae. In this eye, results of histopathologic examination disclosed marked endothelial degeneration and typical guttate excrescences on Descemet's membrane. In contrast, the endothelium in the fellow eye with the essential iris atrophy variant of the iridocorneal endothelial (ICE) syndrome was strikingly different. The endothelial cells were relatively well preserved and exhibited marked pleomorphism, anisocytosis, and flat, occasionally paired oval nuclei. Binucleate cells also were observed. The endothelial monolayer had secreted a new layer of fibrillar extracellular matrix material on the posterior surface of Descemet's membrane. Extracellular matrix material was found interposed between the iris and cornea in zones of synechial closure, and an endothelial membrane was present on the anterior surface of the iris. These observations support the hypothesis that the iris abnormalities in essential iris atrophy are secondary to endothelial proliferation. The endothelial cells displayed neither tonofilaments nor abundant apical microvilli. The latter observation suggests that increased numbers of endothelial microvilli are not responsible for the characteristic specular microscopic picture seen in the ICE syndrome.
Radiographic Differentiation of Cranial Mediastinal Lymphomas from Thymic Epithelial Tumors in Dogs and Cats.

In both dogs and cats, the most common cranial mediastinal masses (CMMs) are lymphoma and thymic epithelial tumors (TETs). Pretreatment differentiation of these tumors using fine needle aspiration or biopsy is essential because lymphomas are treated medically, whereas TETs are treated surgically. The purpose of this retrospective study was to determine whether thoracic radiographic findings can be used to aid clinicians in preliminarily differentiating the two tumor types before cytology or histopathology results become available. Medical records, available cytologic or histologic samples, and thoracic radiographs were evaluated for 62 dogs and 28 cats. Seventeen radiographic criteria were assessed by two examiners, and regression modeling was performed to test for significant predictors of tumor type. In dogs, CMMs with at least two well-defined radiographic margins on a lateral view and CMMs causing a rightward shift of the cardiac silhouette on a ventrodorsal or dorsoventral view were significantly more likely to be TETs than lymphomas (P < .001 and P < .01, respectively). No significant predictive variables were identified in cats. Radiographic findings do not eliminate the need for invasive sampling, but in dogs, they may guide the clinician in providing preliminary information to owners regarding the staging and therapeutic measures that may eventually be recommended.
Factors Influencing Receipt of Interventional Pain Management Among Medicaid Beneficiaries with Cancer.

BACKGROUND Pain is common among cancer patients. Nonclinical factors may affect receipt of pain management among Medicaid beneficiaries with cancer. OBJECTIVES To examine associations of patient characteristics and US state-level Medicaid policies on receipt of interventional pain management among Medicaid beneficiaries with breast or colorectal cancer. STUDY DESIGN A retrospective analysis of 2006-2008 Medicaid claims data. SETTING Claims data from facilities providing care to Medicaid beneficiaries. METHODS Interventional pain management among Medicaid beneficiaries aged 18-64 years with breast or colorectal cancer was identified using procedure codes in Medicaid claims data. State-level Medicaid policy variables included physician visit reimbursements, required patient copayments, and time period for Medicaid eligibility recertification (12 vs. < 12 months). Analyses also examined beneficiary race/ethnicity, age, comorbidities, and cancer treatment. Generalized estimating equations controlling for clustering by state assessed factors influencing receipt of interventional pain management. RESULTS The study included 8,438 Medicaid beneficiaries with breast or colorectal cancer. Colorectal cancer (vs. breast cancer) patients were significantly more likely to receive interventional pain management. Medicaid policies were not significantly associated with receipt of interventional pain services. Among breast cancer patients, older age and non-Hispanic white race/ethnicity were associated with decreased likelihood of receiving interventional pain management; more comorbidities and receipt of breast conserving surgery were associated with increased likelihood. Demographic characteristics were not significantly associated with receipt of interventional pain management among colorectal cancer patients. LIMITATIONS Sample size of Medicare beneficiaries with cancer receiving interventional pain management; limited information included in Medicare claims data. CONCLUSIONS State-level Medicaid policies were not significantly associated with receipt of interventional pain management for breast or colorectal cancer patients; disparities in receipt of these services were observed only for breast cancer patients. These results may help develop policies to enhance access to appropriate pain management services. KEY WORDS Cancer pain, pain management, Medicaid, health care disparities, breast neoplasms, colorectal neoplasms, health policies, physician practice patterns, retrospective studies, claims analyses.
Non-Linear Parameter Imaging with Refinement Techniques

The parameter β is a function of the acoustic nonlinearity of a medium. We previously reported making tomograms of spatial variations in β by using the concept of the parametric acoustic array. We have reconstructed tomograms from two nonlinearly generated secondary waves: 1) a difference-frequency wave and 2) a second-harmonic wave.
Doubling Down When You Should Fold: Immoral Entrenchment in the Face of Crisis

Why do top management teams (TMTs) make decisions in crisis situations that result in further harm to the firm and customers? In answering that question, I incorporate research on moral intensity, ...
The Buffering Effect of Relationships on Combat Exposure, Military Performance, and Mental Health of U.S. Military Soldiers: A Vantage Point for CFTs

This study examined the role of cumulative combat experiences with regard to military performance and conduct and mental health among a sample of young soldiers from the Army STARRS dataset (N = 5,283). Higher levels of cumulative combat experiences were directly related to poorer performance and conduct and a greater likelihood of anxiety, depression, and post-traumatic stress disorder (PTSD). Military performance and conduct served as a linking mechanism between combat experiences and mental health. Using moderated mediation structural equation modeling, relationship disruptions were found to exacerbate the adverse effects of combat experiences; conversely, unit cohesion buffered the impact of combat experiences. Implications for military helping professionals include identifying leverage points for intervention, particularly strengthening the social connections of service members within and outside the military.
So Help Me, God: Religiosity and End-of-Life Choices in a Nationally Representative Sample

Background: Studies show significant associations between the various dimensions of religiousness and end-of-life (EOL) decisions, such as individuals with high religiosity are more likely to choose aggressive care at EOL. However, these studies focused largely on smaller cancer populations. To our knowledge, there is no existing literature about the association between religiosity and EOL decisions within a national sample of older adults. Objective: The objective of this study was to investigate the association between religiosity and advance directive (AD) completion, and among those with an AD, documented EOL care preferences, using a nationally representative sample. Methods: This was an observational study. Descriptive statistics and logistic regression were conducted with 6051 decedents from the Health and Retirement Study using self-reported frequency of religious service attendance, importance of religion, and religious affiliation. Measurements: The dependent variables were AD completion and care preference. The independent variables were self-reported frequency of religious service attendance, importance of religion, and religious affiliation. Results: Protestants and Catholics had significantly lower odds of AD completion, compared with those with no religious preferences. Decedents who reported religion as very important had significantly lower odds of AD completion than decedents who said religion is not too important. Furthermore, decedents who attended religious services at least once a week, compared with those who do not attend, had significantly higher odds of completing an AD. Among those who completed an AD, neither religiosity nor religious affiliation was significantly associated with preference for prolonged care. Conclusions: Our study demonstrates the influence religiosity has on the development of ADs, prompting seriously ill patients' religious needs to be recognized and supported. It further suggests that religious services may provide a good opportunity for promoting knowledge and completion of ADs.
Flow Cytometric, Morphologic, and Laboratory Comparative Study in Patients With Leukocytosis and Cytopenia

Objectives We wanted to evaluate the effectiveness of flow cytometry immunophenotyping (FCI) as a screening test for patients with leukocytosis and cytopenia. Methods We identified 320 patients during August 2016 to December 2016 and evaluated FCI and morphology of peripheral blood smears (PBSs). Results The most common indications for FCI included history of hematologic malignancy (HHM, n = 126), leukocytosis (n = 80), and cytopenia (n = 53). Positive FCI rate was low with a range of 4.4% to 12.5% in patients with absolute neutrophilia regardless of HHM, if cases with circulating blasts were excluded. Patients with absolute lymphocytosis had a 93% positive FCI rate. Patients with HHM and pancytopenia showed a higher incidence of positive FCI findings than patients without HHM and with isolated cytopenia. PBS morphology correlated strongly with FCI (P = .0001). Conclusion PBS evaluation is an accurate and cost-effective screening test. FCI for patients with mature neutrophilia and isolated cytopenia has a very low yield.
Do central state interventions cause urban shrinkage in China

In China, the stories of urban shrinkage have been ignored and obscured by the dazzling urbanization and modernization processes. This paper intends to find out which prefecture-level cities shrank...
What are the competitive effects of invasive species? Forty years of the Eurasian collared-dove in North America

Eurasian collared-doves (Streptopelia decaocto; hereafter ‘collared-doves’) have spread throughout North America since they first colonized Florida in the early 1980s. Here I test for adverse effects of this introduced species on four confamilial potential competitor dove and pigeon species using data from the breeding season (North American Breeding Bird Survey; BBS) and the winter (Audubon Christmas Bird Count; CBC). Within sites of both sets of surveys, correlations between populations of collared-doves and all four potential competitor species have generally been either nonsignificant or positive, indicating a lack of adverse competitive effects due to collared-doves. Similarly, there were no significant differences in population trends of any of the four species in sites where collared-doves were present compared to those where they were not, and there have been no significant declines in population trends of the four species driven by differences in collared-dove abundance in areas where the latter were present. Overall, analyses revealed no negative effects of collared-doves on populations of these potential competitors. Evidence thus far supports a ‘passenger’ rather than a ‘driver’ role for collared-doves in North America, although future monitoring of potential competitor species is warranted, especially if collared-dove populations continue to increase.
Effects of Reduced-Nicotine Cigarettes Across Regulatory Environments in the Experimental Tobacco Marketplace: A Randomized Trial

Introduction Cigarette smoking remains the leading preventable cause of death in the United States. Recent efforts have explored the potential health and policy benefits of reducing nicotine, an addictive component, in combustible cigarettes. To date, an experimental, prospective analysis directly comparing the effects of varying regulatory environments on purchases of multiple products has yet to be conducted. The present study compared real purchasing of conventional cigarettes, reduced-nicotine cigarettes, and a variety of other nicotine and tobacco products across a range of regulatory environments. Methods Participants were assigned to one of five groups, each associated with a different nicotine level (mg of nicotine to g of tobacco) in SPECTRUM investigational cigarettes (15.8mg/g, 5.2mg/g, 2.4mg/g, 1.3mg/g, and 0.4mg/g). Across sessions, participants made real purchases for nicotine/tobacco products in an Experimental Tobacco Marketplace. Each session corresponded with a distinct regulatory environment wherein different nicotine/tobacco products were available for purchase. Results Our results suggest that the primary drivers of cigarette and nicotine purchasing are regulatory environment and the presence/absence of alternative nicotine and tobacco products. Perhaps surprisingly, nicotine level does not appear to be such a driver of purchasing behavior under these experimental conditions. Investigational cigarette purchasing is lowest when other preferred combustible products are available and highest when investigational cigarettes are the only combustible product available for purchase. Conclusions If a reduced-nicotine policy is implemented, great care should be taken in determining and making available less harmful nicotine/tobacco products as the availability of preferred combustible products may result in undesirable levels of purchasing. Implications This is the first experimental study investigating different potential regulatory effects related to a reduced-nicotine policy by examining purchasing across a range of nicotine/tobacco products. Our results suggest the presence of affordable, highly preferred combustible products is likely to maintain tobacco purchasing at undesirable levels. To promote switching to less harmful products, affordable alternate nicotine and tobacco products should be readily available. Finally, our results suggest availability of noncigarette products, not cigarette nicotine level, will most likely affect purchasing of reduced-nicotine cigarettes.
Cytokine storm of a different flavour: The different cytokine signature of SARS-CoV-2, the cause of COVID-19, from the original SARS outbreak.

Abstract Here we present a case series of three patients with COVID-19 (coronavirus disease 2019) who had a cytokine panel that revealed elevation of interleukin-6 (IL-6) but normal levels of interleukin-10 (IL-10), interferon-gamma (INF-γ) and interleukin-8 (IL-8), in contrast to the cytokine signature described in severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). We also documented evidence of a compromised T-cell IFN-γ response in two of these patients.
Impact of HIV‐infection on human somatosensory processing, spontaneous cortical activity, and cortical thickness: A multimodal neuroimaging approach

HIV-infection has been associated with widespread alterations in brain structure and function, although few studies have examined whether such aberrations are co-localized and the degree to which clinical and cognitive metrics are related. We examine this question in the somatosensory system using high-resolution structural MRI (sMRI) and magnetoencephalographic (MEG) imaging of neural oscillatory activity. Forty-four participants with HIV (PWH) and 55 demographically-matched uninfected controls completed a paired-pulse somatosensory stimulation paradigm during MEG and underwent 3T sMRI. MEG data were transformed into the time-frequency domain; significant sensor level responses were imaged using a beamformer. Virtual sensor time series were derived from the peak responses. These data were used to compute response amplitude, sensory gating metrics, and spontaneous cortical activity power. The T1-weighted sMRI data were processed using morphological methods to derive cortical thickness values across the brain. From these, the cortical thickness of the tissue coinciding with the peak response was estimated. Our findings indicated both PWH and control exhibit somatosensory gating, and that spontaneous cortical activity was significantly stronger in PWH within the left postcentral gyrus. Interestingly, within the same tissue, PWH also had significantly reduced cortical thickness relative to controls. Follow-up analyses indicated that the reduction in cortical thickness was significantly correlated with CD4 nadir and mediated the relationship between HIV and spontaneous cortical activity within the left postcentral gyrus. These data indicate that PWH have abnormally strong spontaneous cortical activity in the left postcentral gyrus and such elevated activity is driven by locally reduced cortical gray matter thickness.
A head-to-head comparison of ribodepletion and polyA selection approaches for C. elegans low input RNA-sequencing libraries.

A recent and powerful technique is to obtain transcriptomes from rare cell populations, such as single neurons in C. elegans, by enriching dissociated cells using fluorescent sorting. However, these cell samples often have low yields of RNA that present challenges in library preparation. This can lead to PCR duplicates, noisy gene expression for lowly expressed genes, and other issues that limit endpoint analysis. Further, some common resources, such as sequence specific kits for removing ribosomal RNA, are not optimized for non-mammalian samples. To advance library construction for such challenging samples, we compared two approaches for building RNAseq libraries from less than 10 nanograms of C. elegans RNA: SMARTSeq V4 (Takara), a widely used kit for selecting poly-adenylated transcripts; and SoLo Ovation (Tecan Genomics), a newly developed ribodepletion-based approach. For ribodepletion, we used a custom kit of 200 probes designed to match C. elegans rRNA gene sequences. We found that SoLo Ovation, in combination with our custom C. elegans probe set for rRNA depletion, detects an expanded set of noncoding RNAs, shows reduced noise in lowly expressed genes, and more accurately counts expression of long genes. The approach described here should be broadly useful for similar efforts to analyze transcriptomics when RNA is limiting.
Nonpoint source arsenic contamination of soil and groundwater from legacy pesticides.

Arsenic (As) contamination in wells is common throughout the northeastern United States. It is well documented that lead-arsenate (PbHAsO4 ) pesticides were widely used on fruit tree orchards from the 1890s to 1950s. This study evaluates the potential for As contamination of groundwater from former orchards in Connecticut, where there were over 47,000 orchards in 1935. A proximity analysis involving 189 orchards and 114 domestic wells was conducted to assess the spatial relationship between historic orchards and As in wells. Field studies were then conducted to characterize As and lead (Pb) distributions in soils and wells near historic orchards. The proximity analysis found that the wells with no detected As were further away from historic orchards and had fewer historic orchards within their vicinity when compared with wells that contained As. The field investigations found that elevated levels of As and Pb were widespread in soils from orchards established by 1951, with some As concentrations exceeding 200 ppm. In some soils, As and Pb were leachable at concentrations exceeding USEPA drinking water standards in synthetic precipitation laboratory tests. It was also found that the wells nearest to the impacted soils tended to contain the highest As concentrations, while the wells located in areas that were forested prior to 1970 contained no As. Overall, this study found that As and Pb from legacy pesticide residues are still abundant in former orchard soils and that a strong spatial relationship exists between As-contaminated wells and historic orchards. Greater consideration should be given to historic orchard soils as a potential contributing nonpoint source of As to the groundwater in Connecticut, where domestic well contamination rates are high.
Auditory feedback and speech development.

Publisher Summary This chapter evaluates the role of feedback, particularly auditory feedback, in the development of speech in children. In the recent enthusiasm for exploring rule-governed bases of linguistic competence, the fact that speech is a highly coordinated motor skill has been almost ignored. Competence theories have ruled the imagination of researchers whereas performance data have been grudgingly accepted as the imperfect source from which competence theories are derived. As important as linguistic considerations are, they inevitably take form through an expressive system such as speech, writing, or signing, and such a system could scarcely function without the contribution of feedback, at least during certain stages of development. Under normal circumstances, speech clearly is multiply determined. Speakers acquire the language to which they have been exposed in the presence of different kinds of listeners and in a variety of social and physical situations. Although it is a motor skill, speech is the expression of linguistic codes and communication needs. Speakers talk louder in noise and also to impress a listener with their determination. Choice of words, speech rate, and inflectional pattern are all multiply determined, reflecting the contributions of social and physical variables, as well as the physiological constraints of the speech system. The relationship between forms of feedback and the various parameters of speech production are well worth exploring in future research. The area is an exciting one, as it pertains both to normal and deviant speech development.
Military Health Services Support in Conflict

This chapter summaries the principles and practice of military health service support in conflict. The language for this chapter is chosen for a non-military audience but is consistent with more detailed descriptions contained in military publications and procedures. The chapter covers the breadth of military health services and includes the practice of medicine, nursing, dentistry and those of allied health professions in the relief of suffering in multinational and joint military operations. The chapter will start by placing health in the context of the military environment. It will then describe the organisation and resources required to provide military health services and the military-specific issues associated with the planning, preparation and deployment of health service support to operations. It will conclude by describing the command and control arrangements for the conduct of military health services support operations.
Guest Editorial: Infrared Imaging Systems

This PDF file contains the editorial “Guest Editorial: Infrared Imaging Systems” for OE Vol. 30 Issue 11
SEPARATION OF LONG-CHAIN BASES BY THIN-LAYER CHROMATOGRAPHY; INSTABILITY OF SPHINGOSINE.

Purified sphingosine was resolved into dihydrosphingosine, sphingosine, and a fast-moving component thin-layer chromatography on Silica Gel G. The fast-moving component was generated by the adsorbent, and consisted of a mixture of the cationic forms of dihydrosphingosine and sphingosine. Other sphingosine derivatives gave rise to similar artifacts. Sphingosine formed two degradation products when stored in solution or on thin-layer plates; related long-chain bases with some of their reactive sites blocked did not deteriorate when stored in solution.
Mutations in the hemolytic-phospholipase C operon result in decreased virulence of Pseudomonas aeruginosa PAO1 grown under phosphate-limiting conditions.

Abstract The phospholipase C (PLC) operon of Pseudomonas aeruginosa consists of plcS, which encodes a heat-labile secreted hemolysin, and two in-phase, overlapping genes, plcR1 and plcR2, which may encode Pi-regulatory genes. A 2.8-kilobase-pair deletion mutation in this operon was constructed, and a tetracycline resistance (Tcr) cartridge replaced the deleted sequences. A deletion mutant of strain PAO1 was obtained through recombination between the flanking regions of the mutated cloned PLC operon and the homologous chromosomal regions. The deletion of the chromosomal PLC operon and its replacement by the Tcr cartridge was confirmed by Southern hybridization. The deletion strain, PLC SR, is nonhemolytic. However, it retains PLC activity when measured on a synthetic substrate. A second mutant strain, PLC R, contains a deletion in the plcR genes. This mutant is more hemolytic and produces more enzymatic activity than PAO1. The virulence of both of these mutants was compared with that of PAO1 in the mouse burn model of infection. When mice were infected with cultures grown in a high-Pi medium, there was a 10-fold increase in the 50% lethal dose of the mutants compared with PAO1. In contrast, when the inoculum originated from low-Pi cultures, there was a 200- to 10,000-fold increase in the 50% lethal dose of the mutants over PAO1.
Evaluation of the effect of ruxolitinib on cardiac repolarization: A thorough QT study.

This was a randomized, four-way crossover study that evaluated the effects of placebo, single doses of ruxolitinib 25 and 200 mg, and a single dose of moxifloxacin 400 mg on heart rate-corrected QT interval in healthy subjects. Electrocardiograms (ECGs) and pharmacokinetic samples were obtained on each dosing day; baseline ECGs were taken pre-dose. The primary endpoint was placebo-subtracted change from baseline heart rate-corrected QT (Fridericia formula [ΔΔQTcF]). The ΔΔQTcF for either dose of ruxolitinib ranged from -3.09 to 3.28 milliseconds (1-sided 95% confidence interval of 0.06-6.62 milliseconds). The ΔΔQTcF for moxifloxacin (lower confidence interval) was significantly >5 milliseconds at 1, 2, and 3 hours post-dose. Individual QTcF >450 milliseconds and QTcF from baseline >30 milliseconds following ruxolitinib were similar to placebo. Based on the International Conference on Harmonization E14 guidance, the study results were considered negative for QTc prolongation. In conclusion, ruxolitinib did not have a clinically significant effect on QT interval.
3-D heart contour delineation and motion tracking of ultrasound images using continuous distance transform neural networks

We apply the previously proposed continuous distance transform neural network (CDTNN) to effectively represent the 3-D endocardial (inner) and epicardial (outer) contours and track the motion of the left ventricle (principal pumping chamber) of the heart from ultrasound images. This CDTNN has many good properties as the conventional distance transforms which are suitable for 3-D object representation and deformation estimation. In addition, this continuous and differentiable representation is parametric so that very low memory storage is needed. We have successfully represented the 3-D epicardial and endocardial walls of the left ventricle of the heart using CDTNNs based on 7.5% to 25% of manually traced training data. The absolute error measured compares favorably with the human interobserver variability reported for analyzing distances.
Effects of Perinatal Vitamin B6 Deficiency on Dopaminergic Neurochemistry

: Long-Evans dams were fed either a vitamin B6-deficient or a control diet from day 13–14 of gestation and throughout lactation. A control pair-fed group was also included because of differences in food intake between vitamin B6-deficient and control ad libitum dams. The progeny of vitamin B6-deficient dams had all the classic symptoms of B6 deficiency. These included weight loss, ataxia, tremor, and epileptic seizures. Concentrations of the neurotransmit-terdopamine (DA), and its metabolites 3,4-dihydroxyphen-ylacetic acid (DOPAC) and homovanillic acid (HVA), as well as D-2 dopamine receptor binding, 3,4-dihydroxy-phenylalanine (DOPA) decarboxylase activity, and vitamin B6 levels were measured in the corpus striatum of progeny at 7, 14, and 18 days after birth. Striatal DA and HVA levels were significantly decreased in B6-deficient animals when compared to ad libitum or pair-fed controls. Daily injections of vitamin B6 to deprived animals from the 14th to 18th day after birth improved the abnormal movement and normalized the concentration of DA but not of HVA in corpus striatum. Striatal D-2 dopamine receptor binding using [3H]spiperone as ligand was significantly reduced in 18-day-3old animals as compared to ad libitum and pair-fed controls. No significant differences were found at 14 days. The administration of vitamin B6 to deprived animals did not raise the level of D-2 receptor binding during the period of observation. Scatchard plots indicated that the differences in binding were due to changes in receptor number and not in KD. Corpus striatum DOPA decarboxylase activity with and without the addition of exogenous pyridoxal phosphate was significantly reduced in 14- and 18-day-old animals when compared to pair-fed controls. Vitamin B6 levels in corpus striatum of deprived animals were significantly lower than control at all ages, substantiating the effect of the maternal deprivation. The results of these experiments suggest that perinatal vitamin B6 deficiency produces significant alterations in the development of the dopaminergic system in the corpus striatum of the neonatal rat.
Money and reputation: squandered opportunities of a clinical IR service.

If a tree falls in the woods, does it make a sound? This age-old philosophical question about the difference between reality and perception is apropos for interventional radiologists who have embraced the clinical imperative. If an interventional radiologist evaluates a patient in the clinic, admits the patient for a procedure, and manages the patientʼs care longitudinally as an outpatient, but does not bill for those services, has that interventional radiologist provided nonprocedural clinical care? Of course—but in her eyes only. Her partners and business manager, who are closely watching the practice’s bottom line, see nothing. Also, policy makers and other specialists (who use claims data to track who’s doing what) continue to dismiss the interventional radiologist as a nonclinical proceduralist. Money and professional reputation are at stake, and without better data and charge capture mechanisms to demonstrate that those services are truly being performed, opportunities to enhance both are squandered. In the current issue of JVIR, White et al (1) report the experience of their interventional practice in applying a team-based systems approach to clinical service revenue management. This is a retrospective report from a single academic institution devoid of actual dollar transparency, but nonetheless it frames an important narrative: Interventional radiologists regularly leave legitimate evaluation and management (E&M) nonprocedural claims on the table—dollars that could easily be realized if they simply implemented the same kind of basic billing systems that our clinical colleagues mastered decades ago.
Engineering Surface Plasmon-Polaritons with Hetero- Dielectric Nanolayers for Ultra-long Range Propagation, Anomalous Dispersion, and Nanoscale Confinement

We report our investigation of using hetero-dielectric nanolayers to engineer and control the attenuation, confinement, and dispersion of the symmetric surface plasmon-polariton modes of thin metal film surface plasmon-polariton waveguides.