cssi/SciSciGPT-SciSciNet huggingface dataset:
Pathogenic characteristics and virulence genes of Shigella flexneri 4c in in Minhang district of Shanghai

Objective:To investigate the biochemical characteristics,antibioticresistance and virulence genes of Shigella flexneri 4c isolates in in Minhang district of Shanghai.Methods:Biochemical identification of the strains was performed using API 32E,serotyping using slide agglutination,antimicrobial susceptibility testing using the Kirby-Bauer method and detection of setlA,setlB,sen,ial,ipaH virulence genes using PCR.Results:The S.flexneri 4c isolates,fermenting glucose and with 91.7% strains fermenting mannitol,were found 100% resistant to nalidixicacid,97.2% to rifampicin,88.9% to SMZ/TM,83.3% to tetracycline,83.3% to ampicillin,80.6% isolates possessed resistance to more than a half of antibiotic species.Presence of setlA,setlB,sen,ial ipaH virulence genes was identified among 91.7%,91.7%,100.0%,100.0% and 100.0% of tested isolates.Conclusion:Strong multidrug resistance of S.flexneri 4c isolates has been found in the present study.Susceptibility to gentamicin and norfloxacin was identified.Presence of virulence genes associated with strong pathogenicity is found in a high proportion of isolates.
Book Review: J. P. Das, Consciousness Quest: Where East Meets West: On Mind, Meditation, and Neural Correlates:

J. P. Das, Consciousness Quest: Where East Meets West: On Mind, Meditation, and Neural Correlates, New Delhi: SAGE Publications, 2014, 307 pp.
Current concepts in the design of hydrogels as vitreous substitutes

In this chapter, the optimization of the design of in situ-forming hydrogel vitreous substitutes is discussed. First, a review of the structure and function, development and growth, and biomechanical properties of the vitreous humor is given. This review provides a foundation for designing a biomimetic vitreous substitute. Past and current treatments for vitreous substitution are also discussed. Recent research advances utilizing hydrogels as vitreous substitutes and proposed solutions for the design of vitreous substitutes are discussed in detail. Particular emphasis is given to the use of in situ-forming hydrogels for vitreous substitution and exploiting the swelling properties of hydrogels to reattach the retina.
Clinical phenotyping in selected national networks

Computational methods for the identification of clinical phenotypes from EHR data are needed to advance our understanding of disease, treatments, and drug response.Machine learning approaches that rely on data patterns require fewer clinical domain experts and resources, and meet the growing demand for scalable and portable phenotyping tools.Research networks and phenotype developers should support collaboration and data standards that will enable computational phenotyping derived from data rather than experts. ObjectiveThe combination of phenomic data from electronic health records (EHR) and clinical data repositories with dense biological data has enabled genomic and pharmacogenomic discovery, a first step toward precision medicine. Computational methods for the identification of clinical phenotypes from EHR data will advance our understanding of disease risk and drug response, and support the practice of precision medicine on a national scale. MethodsBased on our experience within three national research networks, we summarize the broad approaches to clinical phenotyping and highlight the important role of these networks in the progression of high-throughput phenotyping and precision medicine. We provide supporting literature in the form of a non-systematic review. ResultsThe practice of clinical phenotyping is evolving to meet the growing demand for scalable, portable, and data driven methods and tools. The resources required for traditional phenotyping algorithms from expert defined rules are significant. In contrast, machine learning approaches that rely on data patterns will require fewer clinical domain experts and resources. ConclusionsMachine learning approaches that generate phenotype definitions from patient features and clinical profiles will result in truly computational phenotypes, derived from data rather than experts. Research networks and phenotype developers should cooperate to develop methods, collaboration platforms, and data standards that will enable computational phenotyping and truly modernize biomedical research and precision medicine.
SE—Structures and Environment: A Dual-reactor Anaerobic System for Complete Treatment of a Food Processing Waste

Abstract Anaerobic technologies are commonly employed for the initial treatment of food processing wastewater; however, they are not typically considered capable of treating wastewater to meet final discharge requirements. To assess the potential of anaerobic technologies to meet discharge requirements, the performance of two dual-reactor high-rate anaerobic systems fed with confectionery wastewater was investigated. The primary reactors in the system were operated at constant hydraulic retention times of 1·6 d. The secondary reactors were operated with hydraulic retention times of 0·8, 1·6, and 3·2 d. The secondary reactors, which were both downflow anaerobic filters, achieved maximum chemical oxygen demand (COD) removal rates when operated at a hydraulic retention time of 1·6 d. The brick-filled downflow anaerobic filter and the plastic-ring-filled downflow anaerobic filter produced average effluent five-day biochemical oxygen demand concentrations of 26 mg l −1 (COD=80 mg l −1 ) and 36 mg l − (COD=112 mg l −1 ), respectively. To examine the enhanced stability provided by the sequential reactor approach, the dual-reactor system was overloaded at 3·5 times the normal COD concentration (8000 mg l −1 ) for an 8 h period. The secondary reactors were able to accommodate the increased organic loading emitted from the primary reactors, maintaining an overall removal efficiency of >994%. The results suggest that full anaerobic treatment of readily degradable food waste streams may be realistic, and that a sequential reactor approach significantly enhances overall process stability.
Abstract A059: Combinatorial proteomic analysis of the receptor programmed cell death (PD)-1 uncovers new checkpoint modulators

Programmed cell death (PD)-1 is one of the most important inhibitory checkpoints in T cells. Antibodies targeting PD-1 have elicited durable clinical responses in multiple tumor types and long-term remissions in some. Nevertheless, response to anti-PD-1 approaches is limited to a small fraction of patients and thus, a more complete understanding of this pathway should provide i) novel biomarkers for potential responders and ii) potential new therapeutic targets for refractory patients. We took an unbiased approach, exploiting high-resolution mass spectrometry, to uncover novel proteins that either interact with the cytoplasmic tail of PD-1 or are dephosphorylated downstream of the PD-1. We identified almost 20 proteins that interacted directly with the tail of PD-1, and approximately 100 proteins that their phosphorylation status was changed upon PD-1 signaling. Two of the more abundant proteins, EFHD2 and SH2D1A, were functionally analyzed for their contribution in mediating PD-1 inhibitory responses. Silencing EFHD2 resulted in abrogation of PD-1 inhibitory effect, including elimination of the ability of PD-1 signaling to inhibit cytokine secretion, cell proliferation, and cellular adhesion. Mechanistically, EFHD2 co-localized with PD-1 in the immunologic synapse, and was necessary for PD-1 clustering. In contrast, silencing SH2D1A augmented PD-1 function while over-expression of the same protein blocked PD-1 effects. We than discovered that SH2D1A physically competed with the phosphatase SHP2 for the same binding site on the tail of PD-1. Studying PD-1 interactome and phosphoproteome has thus identified new proteins that can modulate PD-1 function in opposite ways. These proteins should be further explored as potential targets in cancer. Citation Format: Michael Peled, Adam Mor. Combinatorial proteomic analysis of the receptor programmed cell death (PD)-1 uncovers new checkpoint modulators [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr A059.
A Comprehensive Review of Wraparound Care Coordination Research, 1986–2014

Wraparound is a team-based care coordination strategy for children and youth with complex behavioral health needs and their families. Despite widespread adoption, a review of the literature pertaining to Wraparound has not previously been conducted. To address this gap, we conducted a comprehensive review, ultimately identifying 206 unique Wraparound-related publications in peer-reviewed outlets. We then coded and analyzed the publications’ methods, main foci, measures, and findings. Eighty-three publications (40%) were non-empirical, most of which focused on defining Wraparound and advocating for its use, largely based on its alignment with the System of Care philosophy. Among empirical studies (n = 123; 60%), 22 controlled studies were found, most finding positive or mixed evidence for Wraparound’s effectiveness. Other empirical studies examined implementation issues such as necessary system conditions and measurement and influence of fidelity. Major gaps include rigorous tests of Wraparound’s change mechanisms, workforce development models, peer support, and the use of specific treatments. We conclude that literature produced to date has provided useful information about Wraparound’s core components, program-level and system-level implementation supports, and applicability across systems and populations, as well as preliminary information about effectiveness and cost-effectiveness. The Wraparound research base would, however, benefit from additional studies of the model’s intervention and implementation components, as well as more rigorous effectiveness studies.
Implementing Constitutional Rights for Juveniles: The Parent-Child Privilege in Context

This article advocates for the creation of a parent-child privilege by focusing on the parental contribution to raising their children. The article argues that children cannot fully exercise their constitutional rights without being able to confide freely in their parents and consult them before waiving rights and while working with their attorneys. I begin by describing the current state of privilege law and suggest that there is already a “de facto” tendency to observe a parent-child privilege. I show that courts have failed to distinguish among three distinctive kinds of confidences: (1) testimony concerning confidences from a minor child to a parent; (2) testimony concerning confidences from adult children to parents; (3) testimony concerning confidences from parents to their children; and have failed to distinguish all three from testimony not based on confidences at all. The first category should be at the heart of any parent-child privilege. Finally, I provide three justifications for recognizing an official parent-child privilege: 1) parents’ interest in a parent-child relationship without governmental intervention, 2) parents serving as intermediaries between their children and professionals working with their children, and 3) the child’s ability to employ his constitutional rights only with open parental communication.
Incidence of mucositis in patients treated with mTOR inhibitor-based regimens and correlation to treatment response.

e13575 Background: Mucositis is a well-known side effect of mTOR inhibitor (temsirolimus) treatment of cancer patients, limiting the use of mTOR inhibitors. We investigated whether combination trea...
A comprehensive analysis of myocardial substrate preference emphasizes the need for a synchronized fluxomic/metabolomic research design

The heart oxidizes fatty acids, carbohydrates, and ketone bodies inside the tricarboxylic acid (TCA) cycle to generate the reducing equivalents needed for ATP production. Competition between these ...
Is There a Church-Turing Thesis for Social Algorithms?

It is well known that how an individual acts in a specific situation depends not only on her preferences (and her means) but also on what she believes. If she believes a restaurant is open, she will go to it, assuming she likes that restaurant and she has the means, e.g., transportation. But if she knows it is not open, then her liking becomes irrelevant.
Oxalobacter formigenes -associated host features and microbial community structures examined using the American Gut Project

Increasing evidence shows the importance of the commensal microbe Oxalobacter formigenes in regulating host oxalate homeostasis, with effects against calcium oxalate kidney stone formation, and other oxalate-associated pathological conditions. However, limited understanding of O. formigenes in humans poses difficulties for designing targeted experiments to assess its definitive effects and sustainable interventions in clinical settings. We exploited the large-scale dataset from the American Gut Project (AGP) to study O. formigenes colonization in the human gastrointestinal (GI) tract and to explore O. formigenes-associated ecology and the underlying host–microbe relationships. In >8000 AGP samples, we detected two dominant, co-colonizing O. formigenes operational taxonomic units (OTUs) in fecal specimens. Multivariate analysis suggested that O. formigenes abundance was associated with particular host demographic and clinical features, including age, sex, race, geographical location, BMI, and antibiotic history. Furthermore, we found that O. formigenes presence was an indicator of altered host gut microbiota structure, including higher community diversity, global network connectivity, and stronger resilience to simulated disturbances. Through this study, we identified O. formigenes colonizing patterns in the human GI tract, potential underlying host–microbe relationships, and associated microbial community structures. These insights suggest hypotheses to be tested in future experiments. Additionally, we proposed a systematic framework to study any bacterial taxa of interest to computational biologists, using large-scale public data to yield novel biological insights.
Numerical schemes for SDEs with time delay using the Wong-Zakai approximation

Will a spectral approximation of Brownian motion lead to higher-order numerical methods for stochastic differential equations as the Karhunen-Loeve truncation of a smooth stochastic process does?
A Numerical and Experimental Investigation of Flow Separation Control over a Wall-Mounted Hump Model

Numerical simulations and wind tunnel experiments were performed to investigate flow separation and its control over a wall-mounted hump model. Three-dimensional, unsteady fluid dynamic simulations were used to capture the relevant flow physics of unsteady flow separation and its control via active and passive flow control methods. Surface pressure measurements and surface oilflow visualization were obtained in the experiments. Current measurements documented a considerably thinner incoming boundary layer, but similar pressure distribution, compared to the reference data reported in the CFD (Computational Fluid Dynamics) Validation (CFDVAL 2004) Experiments. Consistent with the data available in the literature, numerical simulations predicted a longer separation bubble, which manifested itself as a shift in the pressure distributions. Streamwise vortices generated by passive vortex generators increased the suction pressure and provided substantial pressure recovery. Numerical simulations of vortex generators qualitatively predicted the effects of control, and revealed patterns of attached/separated flow regions. On the other hand, active flow control using steady discrete jets reduced, but was not able to eliminate, flow separation for the tested configuration. Although the major disagreement between the numerical and experimental results was in the pressure recovery region due to the inaccurate prediction of separation bubbles, the relative pressure recoveries from the baselines were comparable. Surface oilflow visualization and simulated surface streamlines were qualitatively in good agreement revealing the key flow features.
Occurrence and transformation of veterinary antibiotics and antibiotic resistance genes in dairy manure treated by advanced anaerobic digestion and conventional treatment methods.

Manure treatment technologies are rapidly developing to minimize eutrophication of surrounding environments and potentially decrease the introduction of antibiotics and antibiotic resistant genes (ARGs) into the environment. While laboratory and pilot-scale manure treatment systems boast promising results, antibiotic and ARG removals in full-scale systems receiving continuous manure input have not been evaluated. The effect of treatment on ARGs is similarly lacking. This study examines the occurrence and transformation of sulfonamides, tetracyclines, tetracycline degradation products, and related ARGs throughout a full-scale advanced anaerobic digester (AAD) receiving continuous manure and antibiotic input. Manure samples were collected throughout the AAD system to evaluate baseline antibiotic and ARG input (raw manure), the effect of hygenization (post-pasteurized manure) and anaerobic digestion (post-digestion manure) on antibiotic and ARG levels. Antibiotics were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and the ARGs tet(O), tet(W), sul1 and sul2 were analyzed by quantitative polymerase chain reaction (Q-PCR). Significant reductions in the concentrations of chlortetracycline, oxytetracycline, tetracycline and their degradation products were observed in manure liquids following treatment (p < 0.001), concomitant to significant increases in manure solids (p < 0.001). These results suggest sorption is the major removal route for tetracyclines during AAD. Significant decreases in the epimer-to-total residue ratios for chlortetracycline and tetracycline in manure solids further indicate degradation is desorption-limited. Moreover, sul1 and sul2 copies decreased significantly (p < 0.001) following AAD in the absence of sulfonamide antibiotics, while tetracyclines-resistant genes remained unchanged. A cross-sectional study of dairy farms utilizing natural aeration and liquid-solid separation treatments was additionally performed to compare levels of antibiotics and ARGs found in AAD with the levels in common manure management systems. The concentration of antibiotics in raw manure varied greatly between farms while minimal differences in ARGs were observed. However, significant (p < 0.01) differences in the levels of antibiotics and ARGs (except tet(W)) were observed in the effluents from the three different manure management systems.
Neuronal Intermediate Filaments and Neurodegenerative Diseases

Neuronal intermediate filaments (IFs) are major components of the cytoskeleton in neurons and are composed of a family of neuronal IF proteins that include peripherin, α-internexin, and neurofilament triplet proteins (NFTPs), designated NF-L, NF-M, and NF-H for low, medium, and high molecular weight subunits, respectively. NFTPs are determinants of axonal caliber, while α-internexin may play a role in neuronal regeneration and peripherin in proper development of a defined population of sensory neurons. The composition and proper stoichiometry of these proteins are important for IF assembly and transport. Abnormal IF accumulations in neuronal perikarya and proximal axons are pathological hallmarks of many neurodegenerative diseases. Studies of transgenic mouse models as well as identification of NF-H mutations in sporadic amyotrophic lateral sclerosis (ALS) and NF-L mutations in Charcot-Marie-Tooth disease indicate that neuronal IFs have a direct role in pathogenesis of these diseases. Overexpression of individual NFTP subunit or peripherin in transgenic mice causes abnormal accumulation of IFs in motor neurons and motor dysfunction, reminiscent of ALS, whereas overexpression of α-internexin causes Purkinje cell death and motor coordination deficits. Deletion of NF-L or overexpression of NF-H extends the lifespan of transgenic mice expressing mutated Cu/Zn superoxide dismutase (SOD1), suggesting that NFTPs may also contribute to SOD1 mutation-linked ALS. The misaccumulated IFs in neuronal perikarya and proximal axons are disorganized and aberrantly phosphorylated. The kinases and phosphatases that are known to control phosphorylation of NFTPs are deregulated in the disease state. Studies of transgenic mouse models show that axonal transport of neuronal IFs and other cellular components is impaired in the disease state, ultimately leading to neurodegeneration. Formation of disorganized and aberrantly phospohorylated IFs, changes in stoichiometric levels of neuronal IF proteins due to dysregulation of their gene expression, and reduced levels of functional motor proteins may contribute in part to this defective axonal transport. Recent studies raise the possibility that cis-acting and trans-acting determinants of NF-L mRNA stability may also be involved in degeneration of motor neurons. Taken together, these data suggest that abnormal IF accumulations in neurons may not simply be the by-products of neurodegenerative diseases but may instead play a contributory role in pathogenesis of these diseases.
Judging the Ends-The Good

Making moral decisions is a vastly complicated process. And in great degree the complexity is due to the various meanings that moral terms have. Learning to make moral decisions is, in large measure, learning to use words less ambiguously in order to be able to apply them properly.
Six new species of Miconia (Miconieae, Melastomataceae) from the Andes

The eastern slopes of the Andes harbor some of the greatest amount of biodiversity, much of which remains undescribed in the scientific literature. Here, we describe six new species of Miconia from the Andes, encompassing the southernmost extent of the mountain range from Peru to Bolivia. The new species include Miconia cernuiflora, Miconia cinnabarina, Miconia dimorphotheca, Miconia dulcis, Miconia farfanii, and Miconia paucartambensis. Each species is compared with similar species. For each species, we include a diagnostic illustration, conservation assessment and range map. The number of species described underscores the continued need for exploration and field studies, especially as many of these species have extremely restricted distributions.
Phosphatidylinositol 4,5-Bisphosphate (PIP2) Regulate KCNQ3 K+ Channels Via Multiple Sites Of Action

Phosphatidylinositol 4,5-bisphosphate (PIP2) regulates the function of many ion channels, including M-type (KCNQ, Kv7) K+ channels; however the molecular mechanisms involved remain unclear. To resolve this issue for M-channels, we focused on the KCNQ3 subtype that has the highest apparent affinity of PIP2 and performed extensive mutagenesis in regions suggested to be involved in PIP2 interactions among the KCNQ family. Using the zebrafish (Danio rerio) voltage-sensitive phosphatase to deplete PIP2 as a probe, we found that PIP2 modulates KCNQ3 channels through four different domains: 1) the A-B helix linker that we previously identified as important for both KCNQ2 and KCNQ3, 2) the junction between S6 and the A helix, 3) the S2-S3 linker and 4) the S4-S5 linker. We found that PIP2 interactions within none of these domains were coupled to the voltage dependence of activation. Extensive homology modeling and docking simulations between the wild-type or mutant KCNQ3 channels and PIP2 correlated with the experimental data. Our results indicate that PIP2 modulates KCNQ3 channel function by interacting synergistically with a minimum of four cytoplasmic domains.
WHO-AVLT recognition trial: Initial validation for a new malingering index for Spanish-speaking patients

Several methods for identifying suboptimal effort on Spanish neuropsychological assessment have been established. The purpose of this retrospective study was to determine whether recognition data from the WHO-AVLT could be employed for determination of malingering in a Spanish-speaking sample. Sixteen subjects in litigation, 25 neurological patients, and 14 healthy controls completed neuropsychological testing. All subjects completed the Test of Memory Malingering (TOMM). Inclusion criteria for neurological patients and controls included performance above the standard TOMM cutoff. Subjects in litigation were classified as probable malingering, through lower than cutoff performance on the TOMM and at least one other performance validity measure. Cut-off scores for classification of malingering were determined based on the number of recognition hits on the WHO-AVLT. The probable malingering group performed significantly worse than both groups on recognition hits. A score <10 was determined to be the optimal group cutoff, with 56.25% sensitivity and specificity greater than 92%. A combination score of 14 increased sensitivity to 68.75%. These findings provide initial validation of a new malingering index, based on the number of hits on the WHO-AVLT recognition trial. This index will provide valuable information to neuropsychologists conducting forensic or clinical evaluations on Spanish-speaking individuals.
Causal Inference and Counterfactual Reasoning (3hr Tutorial)

As computing systems are more frequently and more actively intervening to improve people's work and daily lives, it is critical to correctly predict and understand the causal effects of these interventions. Conventional machine learning methods, built on pattern recognition and correlational analyses, are insufficient for causal analysis. This tutorial will introduce participants to concepts in causal inference and counterfactual reasoning, drawing from a broad literature from statistics, social sciences and machine learning. We will first motivate the use of causal inference through examples in domains such as recommender systems, social media datasets, health, education and governance. To tackle such questions, we will introduce the key ingredient that causal analysis depends on---counterfactual reasoning---and describe the two most popular frameworks based on Bayesian graphical models and potential outcomes. Based on this, we will cover a range of methods suitable for doing causal inference with large-scale online data, including randomized experiments, observational methods like matching and stratification, and natural experiment-based methods such as instrumental variables and regression discontinuity. We will also focus on best practices for evaluation and validation of causal inference techniques, drawing from our own experiences. After attending this tutorial, participants will understand the basics of causal inference, be able to appropriately apply the most common causal inference methods, and be able to recognize situations where more complex methods are required.
The Sharing Economy and the Allocation of Urban Space

This short essay uses four interrelated issues as a framework for examining recent challenges posed by the sharing economy, particularly for urban areas. First, in the realm of short-term rentals there is increasing concern – and a growing set of studies that support it – that as these rentals proliferate across municipalities they are moving existing housing off of the long-term rental market, exacerbating affordability crises in many cities. Second, there is a related concern that short-term rentals are changing the character of existing neighborhoods and undermining the goals of local planning and zoning. Third, in the realm of transportation network companies, a growing body of research links Uber and Lyft to increased traffic congestion in dense urban areas. And fourth, ridesharing services threaten to pull riders away from public transportation, further exacerbating congestion while simultaneously harming cash-strapped transportation systems. The essay considers these challenges in light of the contributions to the recently published Cambridge Handbook of the Law of the Sharing Economy, of which the author is a co-editor, drawing on insights from those contributions and highlighting chapters within the volume of most relevance for zoning and planning law. It then surveys potential responses to these challenges, drawing both on the Handbook and on recent developments in a small number of representative jurisdictions.
Development of the Highly Processed Food Withdrawal Scale for Children

Abstract Introduction Highly processed foods (with added fats and/or refined carbohydrates) may trigger an addictive-like process, including withdrawal when these foods are reduced. Withdrawal is marked by affective, cognitive, and physical symptoms that may hinder dietary change. A recently developed scale of highly processed food withdrawal in adults (ProWS) provides evidence for this construct. Children commonly consume highly processed foods, but no measures currently exist to examine highly processed food withdrawal in children. The purpose of this study was to develop a measure (ProWS-C) to assess for signs of highly processed food withdrawal in children. Methods Parents who had recently attempted to reduce their child's highly processed food consumption were recruited through an online crowdsourcing platform. 304 parents (56.9% mothers) reported on their 3-11-year-old children (63.8% male). The ProWS-C was designed to reflect parents' observations of child behavior. Internal consistency and validity were evaluated using the Dimensional Yale Food Addiction Scale Version 2.0 for Children (dYFAS-C 2.0.), Children's Food Neophobia Scale-Modified (CFNS), and body mass index (BMI) silhouettes. Results Exploratory factor analysis revealed a one-factor structure with 21 items (α = 0.94). The ProWS-C demonstrated convergent validity with more child food addiction symptoms (r = 0.55, p Discussion The ProWS-C provides preliminary evidence for highly processed food withdrawal in children and appears to be a psychometrically sound tool for assessing parent-reported withdrawal symptoms in children. Illuminating specific challenges families face when reducing highly processed foods may improve parents’ ability to help their children make sustainable dietary changes.
Individual species and cumulative mixture relationships of 24-hour urine metal concentrations with DNA methylation age variables in older men

Abstract Background Globally, toxic metal exposures are a well-recognized risk factor for many adverse health outcomes. DNA methylation-based measures of biological aging are predictive of disease, but have poorly understood relationships with metal exposures. Objective We performed a pilot study examining the relationships of 24-h urine metal concentrations with three novel DNA methylation-based measures of biological aging: DNAmAge, GrimAge, and PhenoAge. Methods We utilized a previously established urine panel of five common metals [arsenic (As), cadmium (Cd), lead (Pb), manganese (Mn), and mercury (Hg)] found in a subset of the elderly US Veterans Affairs Normative Aging Study cohort (N = 48). The measures of DNA methylation-based biological age were calculated using CpG sites on the Illumina HumanMethylation450 BeadChip. Bayesian Kernel Machine Regression (BKMR) was used to determine metals most important to the aging outcomes and the relationship of the cumulative metal mixture with the outcomes. Individual relationships of important metals with the biological aging outcomes were modeled using fully-adjusted linear models controlling for chronological age, renal function, and lifestyle/environmental factors. Results Mn was selected as important to PhenoAge. A 1 ng/mL increase in urine Mn was associated with a 9.93-year increase in PhenoAge (95%CI: 1.24, 18.61, p = 0.03). The cumulative urine metal mixture was associated with increases in PhenoAge. Compared to a model where each metal in the mixture is set to its 50th percentile value, every one-unit increase of the cumulative mixture with each metal at its 70th percentile was associated with a 2.53-year increase in PhenoAge (95%CI: 0.10, 4.96, P Conclusion Our results add novel evidence that metals detected in urine are associated with increases in biological aging and suggest that these DNA methylation-based measures may be useful for identifying individuals at-risk for diseases related to toxic metal exposures. Further research is necessary to confirm these findings more broadly.
COVID-19 poses a riddle for the immune system.

It is unclear why people’s immune response to the SARS-CoV-2 coronavirus varies so widely. Tracking patient responses over time sheds light on this issue, and has implications for efforts to predict disease severity. Variations in patient defence responses tracked over time.
Remembering Empires: Between Civilisational Nationalism and Post-National Pluralism

This chapter explores the uses and abuses of imperial nostalgia. It proposes two categories: “civilizationalist nationalism” and “post-national pluralism.” The former is defined as a form of cultural nationalism which cites an imagined, imperial golden age of religious and racial purity. This mode of remembering empire informs right-wing nationalist and violent extremist platforms in both the West and the Islamicate world. Post-national pluralism, on the other hand, invokes imperial cosmopolitanism as inspiration for managing diversity today. Less egregious than civilizationalist nationalism, it nonetheless can take hyperbolic forms which gloss over the shortcomings of Habsburg and Ottoman multiculturalism, violent patterns of transition from empire to nation-state, and their traumatic legacies. Offering a synthetic overview of this volume’s contributions as a corrective to these reductionist modes of remembrance, the chapter concludes with a plea for embrace of our complexity, past and present alike.
Cold-induced vasodilation in abstinent smokers with and without a 12-hour nicotine patch.

This study was designed to identify the effects of a 12-h nicotine patch administration on cold induced vasodilation (CIVD) in healthy young chronic smokers following 16 h of abstinence from smoking. Two laser Doppler probes and temperature thermocouples were placed on the dorsal part of the distal phalanx of the middle and ring fingers of 7 smokers (>12 cigarettes/day). Following 16 h of abstinence from smoking, smokers were tested with and without administration of a 21 mg transdermal nicotine patch (NicoDerm® ). Each participant's right hand was immersed in cold (~5°C) water for 40 min. Cutaneous vascular conductance (CVC) was calculated from non-invasive arterial finger blood pressure and skin blood flow and expressed as a percentage of peak CVC observed during hand skin heating to 44°C. For comparison purposes, the CIVD response of a non-smoking cohort without nicotine patch (n = 10) was also examined. Baseline CVC was similar in smokers and non-smokers (27.8 ± 12.6 CVC % peak). The initial vasoconstriction during cold-water immersion decreased skin blood flow to 4.0 ± 3.9 CVC % peak in both smokers and non-smokers. The onset of CIVD in smokers (4.5 ± 1.5 min) was delayed compared to non-smoker (3.3 ± 0.8 min, p < .05). The area under the CVC %peak-time curve during cold-water immersion averaged 1250 ± 388 CVC %peak · min in non-smokers which was larger (p < .05) than smokers with or without nicotine (789 ± 542 and 862 ± 517 CVC %peak · min, respectively). Chronic smoking impaired the CIVD response to cold-water immersion of the hand; however, the impaired CIVD response in 16 h of abstinence from smoking was not influenced by application of a 21 mg transdermal nicotine patch.
High Quality Imaging and Dosimetry of Yttrium-90 (90Y) Radioembolization Using a SiPM-Based PET/CT scanner

599 Objectives: Yttrium-90 radioembolization (90Y RE) is a treatment modality for primary and secondary hepatic malignancies. Personalized dosimetry is crucial and aims for maximum treatment effect while keeping toxicity acceptably low. Dose calculation methods are based on empirical evidence with regard to efficacy and safety, but do not take the radiation absorbed dose in the tumor(s) or the normal liver tissue into account. Here we evaluated the image quality of 90Y post RE scans using a SiPM-based PET/CT scanner (Discovery MI) compared to standard of care pre-therapy 99mTc MAA SPECT/CT. We assessed the accuracy for both distribution and dosimetry and compared the absorbed dose in the tumor(s) and normal liver tissue in the pre- and post-therapy imaging. Methods: SurePlan (MIM) software (version 6.7.10, MIM Software, Cleveland, OH) was used to analyze the 99mTc MAA SPECT/CT and 90Y PET/CT imaging. Tumor volume and normal liver tissue were contoured on the diagnostic CT images and then registered to the 99mTc MAA SPECT/CT and the post-therapy 90Y PET/CT images respectively. Image quality of the lesions detected with digital PET/CT was compared to 99mTc-MAA SPECT/CT using the 5-point Likert scale. All PET images were acquired for 30 minutes and reconstructed in 10, 15 and 20 minute datasets. Two nuclear medicine physicians reviewed all scans independently. Results: We enrolled eight patients (age range 55 - 88 years, mean age 67 years; 5 males and 3 females) treated for primary and secondary liver malignancies. The median administered activity was 2.42 (0.2-4.4) GBq. Mean dose of tumor computed from 99mTc MAA SPECT/CT was 82.4 Gy versus 83.1 Gy from post-therapy 90Y PET/CT. There was no significant average difference between Tumor-SPECT/CT and Tumor-90Y PET/CT doses (t = 0.78, P=0.938). On average, Tumor-SPECT/CT scores were 0.7 Gy higher than Tumor-90Y PET/CT doses (95% CI [-18, 20]). For normal liver tissue a mean dose of 21.3 Gy was found in the 99mTc MAA SPECT/CT images and 17.8 Gy for 90Y PET/CT (T= -1.114, P=0.302). On average, normal liver tissue doses in the 99mTc MAA SPECT/CT were 3.5Gy lower than 90Y PET/CT doses (95% CI [-11, 4]). The tumor uptake of pre- and post-therapy imaging was well correlated in all patients. For 90Y PET/CT imaging, the best image quality was found to be at 20 min scan time (Likert-Scale 4.5 ± 0.5) vs. 15 min Likert-Scale 4 ± 0.6 and 10 min Likert-Scale 2 ± 0.6. Conclusions: Our preliminary data show excellent image quality from digital 90Y PET/CT at a reduced scan time of 20 minutes, and SurePlan (MIM) software computed no significant divergent tumor or normal liver tissue doses for 99mTc MAA SPECT/CT and 90Y PET/CT. However, more patients have to be evaluated to confirm these findings. The faster imaging time may allow for inclusion of 90Y PET/CT in routine clinical workflows.
Clinical prediction is at the heart of preventing birth trauma and pelvic floor disorders for individual women.

The purpose of this article is to understand that the majority of studies investigating the role of risk factors for maternal birth trauma and pelvic floor disorders are designed using causal inferential statistical methods and have not been designed to investigate the more useful goal of clinical prediction. A review of the literature was conducted to describe notable causal and predictive associations between risk factors and maternal birth trauma outcomes. Examples were obtained to illustrate and contrast differences in clinical usefulness between causal and predictive models. Effects of pregnancy and childbirth on the risk of maternal birth trauma outcomes and subsequent pelvic floor disorders are an area of profound investigation. Numerous observational studies provide evidence that pregnancy and childbirth play a causal role in the increasing prevalence of these outcomes, and clinicians must rely on this observational evidence to guide decisions about preventing maternal birth trauma and pelvic floor disorders. However, there are important differences between the design and evaluation of models for a predictive context including: study design goals, inclusion or exclusion of candidate risk factors, model evaluation and the additional need to assess model error. This article contrasts how causal and predictive modeling approaches are different and argues that indiscriminately modeling risk factors for birth trauma and pelvic floor disorder outcomes is costly to women.
Spatial, temporal, and demographic patterns in prevalence of smoking tobacco use and initiation among young people in 204 countries and territories, 1990–2019

Summary Background Universally, smoking cessation rates among established smokers are poor. Preventing young people from starting use of and becoming addicted to tobacco products remains a key strategy to end the tobacco epidemic. Previous country-specific studies have found that initiation of smoking tobacco use occurs predominantly among young people and have found mixed progress in reducing the prevalence of smoking tobacco use among young people. Current and comparable estimates for all countries are needed to inform targeted interventions and policies. Methods We modelled two indicators: prevalence of current smoking tobacco use among young adults aged 15–24 years, and the age at which current smokers aged 20–54 years in 2019 began smoking regularly. We synthesised data from 3625 nationally representative surveys on prevalence of smoking and 254 on age at initiation. We used spatiotemporal Gaussian process regression to produce estimates of the prevalence of smoking and age of initiation by sex, for 204 countries and territories for each year between 1990 and 2019. Findings Globally in 2019, an estimated 155 million (95% uncertainty interval 150–160) individuals aged 15–24 years were tobacco smokers, with a prevalence of 20·1% (19·4–20·8) among males and 4·95% (4·64–5·29) among females. We estimated that 82·6% (82·1–83·1) of current smokers initiated between ages 14 and 25 years, and that 18·5% (17·7–19·3) of smokers began smoking regularly by age 15 years. Although some countries have made substantial progress in reducing the prevalence of smoking tobacco use among young people, prevalence in 2019 still exceeds 20% among males aged 15–24 years in 120 countries and among females aged 15–24 years in 43 countries. Interpretation The fact that most smokers start smoking regularly before age 20 years highlights the unique window of opportunity to target prevention efforts among young people and save millions of lives and avert health-care costs in the future. Countries can substantially improve the health of their populations by implementing and enforcing evidence-based tobacco control policies that prevent the next generation from initiating smoking. Funding Bloomberg Philanthropies.
Cognitive behavioral therapy for depressive disorders: Outcomes from a multi-state, multi-site primary care practice.

Abstract Background Individuals with depressive disorders often present to and seek treatment in primary care. Integrated behavioral health services within this setting can improve access to evidence-based cognitive behavioral therapy (CBT). However, limited information exists on the effectiveness of CBT for depression in primary care. Methods Of the 1,302 participants with a primary depressive disorder referred by their primary care provider, 435 endorsed moderate to severe depression at baseline and engaged in at least one CBT session. A psychotherapy tracking database was used to collect relevant data, which included demographics, clinical characteristics, treatment outcomes, and CBT intervention use. Results Participants with moderate to severe depression who participated in CBT reported a significant decrease in depression and anxiety symptoms at the end of treatment (p ≤ .001, d = 0.52–0.78). Rates of reliable change, response, and remission and types of CBT interventions used differed between major and persistent depressive disorders. Limitations Multiple limitations must be noted, which are related to the naturalistic study design, inclusion and exclusion criteria, sample operationalization, symptomatic measurement, time-limited and focused assessment, data collection strategies, and psychological services. Together, these temper the conclusions that can be drawn. Conclusion Significant reductions in depression and anxiety symptoms were reported by participants with depressive disorders who engaged in short-term CBT within primary care. This study indicates that CBT can be implemented within primary care and suggests that primary care patients with depression can benefit from integrated psychological services, supporting population-based models of care.
A Knowledge Network-Based Approach to Facilitate Annotation of Clinical Pathway Component Clusters

Mining electronic health records (EHRs) to identify contextually related clinical concept clusters that tend to co-occur temporarily and consistently could improve data-driven clinical pathway (CP) construction. However, the automatic extraction of contextually related clinical concept clusters contains a vast amount of irrelevant information. Hence, this paper proposes a knowledge network-enabled literature-based discovery (LBD) approach to remove noise from clusters. The authors used published literature to filter spurious concepts from the clusters and used data from the US Department of Veterans Affairs’s major depressive disorder (MDD) cohort of Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) for their experimentation. The approach was applied to 2,967 clusters extracted from the MDD OEF/OIF database. The experimental results demonstrate that the proposed approach can filter 94% of the irrelevant information. Moreover, the authors applied various network mining algorithms to analyze the clusters and demonstrated that LBD, along with network mining techniques, is a useful method for finding accurate contextually related clinical concept clusters. This could help domain researchers perform advanced analytics in CPs.
Implementation of Screening, Brief Intervention, and Referral to Treatment (SBIRT) Training in Large Cohorts of Second Year Medical Students

Substance use disorders are debilitating disorders with far reaching effects. However, many healthcare providers do not receive sufficient training on how to identify or respond to individuals who ...
Observing Performance Dynamics Using Parallel Profile Snapshots

Performance analysis tools are only as useful as the data they collect. Not just accuracy of performance data, but accessibility, is necessary for performance analysis tools to be used to their full effect. The diversity of performance analysis and tuning problems calls for more flexible means of storing and representing performance data. The development and maintenance cycles of high performance programs, in particular, stand to benefit from exploration of and expansion of the means used to record and describe program execution behavior. We describe a means of representing program performance data via a time or event delineated series of performance profiles, or profile snapshots, implemented in the TAU performance analysis system. This includes an explanation of the profile snapshot format and means of snapshot analysis.
Predictors of Perforation in Necrotizing Enterocolitis |[dagger]| 1090

Objective: Reliance on abdominal radiographs to diagnose intestinal perforation secondary to necrotizing enterocolitis in premature infants may delay operative intervention and increase the short and longterm complications. The objective of the study was to determine whether clinical and hematological alterations predict impending perforation in neonates with necrotizing enterocolitis.