cssi/SciSciGPT-SciSciNet huggingface dataset:
Neural control of feeding behavior Overview and clinical correlations

AgRP= : Agouti-related protein; ARC= : arcuate nucleus; BDNF= : brain-derived neurotrophic factor; CART= : cocaine- and amphetamine-regulated transcript; CB1= : cannabinoid 1; CRH= : corticotrophin-releasing hormone; GABA= : γ-aminobutyric acid; MC4R= : melanocortin 4 receptor; MCH= : melanin-concentrating hormone; MSH= : melanocyte-stimulating hormone; NPY= : neuropeptide Y; POMC= : pro-opiomelanocortin; PVN= : paraventricular nucleus; TRH= : thyrotrophin-releasing hormone. The control of food intake and energy metabolism depends on the interaction among energy homeostasis, emotional factors (including the hedonic aspects of food), and environmental cues. These complex interactions involve a neural network distributed throughout the forebrain and brainstem and are mediated by multiple chemical signals. The hypothalamus is a nodal component of this network and contains several nuclei that exert a bidirectional homeostatic control on food intake and metabolism in response to peripheral signals that reflect the absorptive state and energy reserve. The insular cortex, orbitofrontal cortex, nucleus accumbens, amygdala, and dopaminergic ventral tegmental area neurons have a key role in control of feeding behavior in response to the reward or hedonic aspects of food. Over the past several years, there has been extensive research on the mechanisms controlling food intake and energy metabolism. Studies in experimental animals and functional neuroimaging studies in humans have provided insight into the complex interactions between the homeostatic and hedonic control of feeding behavior. These studies are relevant given the importance of obesity as a public health problem, and have identified several potential targets for treatment of this disorder. This experimental information also provides insight into the mechanisms underlying abnormal feeding behavior in neurologic disorders such as hypothalamic lesions and frontotemporal dementia. There are excellent reviews on homeostatic control of food intake and energy metabolism by the hypothalamus1–7 and the role of brain reward circuits in regulating feeding behavior.1,8–13 Only selected aspects will be emphasized here. The homeostatic control of food intake depends on long-loop mechanisms involving peripheral humoral and neural signals that are processed in the hypothalamus. Recent experimental studies2–7 have greatly refined the classic model of a “satiety” center, located in the ventromedial hypothalamus and a “feeding center,” located in the lateral hypothalamus, which was originally based on …
Monocyte-Macrophages, Granulocyte-Macrophage Colony-Stimulating Factor, and Prolonged Survival Among Patients with Acute Myeloid Leukemia and Stem Cell Transplants

Recombinant GM-CSF has been recently shown to prolong survival of elderly patients with acute myeloid leukemia (AML) by reducing the rate of induction therapy-related mortality. In a prospective, randomized, placebo-controlled, double-blind, multicenter study conducted by the Eastern Cooperative Oncology Group in the United States, granulocyte-macrophage colony-stimulating factor (GM-CSF) was given only to those patients who had hypocellular or remission marrow on day 10 of one or two cycles of standard induction therapy. Although the administration of GM-CSF significantly reduced a wide range of adverse events, the main benefit of this cytokine seems to be mediated by a reduction in sepsis. A similarly designed study, conducted by the Southwest Oncology Group in a directly comparable AML patient population with use of granulocyte colony-stimulating factor (G-CSF) as the supportive cytokine, showed no survival benefit and no reduction in the rates of serious or lethal sepsis. In most current clinical situations, GM-CSF and G-CSF are indistinguishable both in terms of efficacy and toxicity. GM-CSF and G-CSF have very different impacts on the survival of patients with AML. The stimulation of monocyte-macrophage function and proliferation by GM-CSF may mediate the selective benefit of GM-CSF in patients with AML and stem cell transplants. GM-CSF merits further study as therapy for and/or protection against opportunistic sepsis in patients with cancer and will be included in a number of International Oncology Study Group protocols.
Gastroduodenal motility disturbances in man.

The specialised regions of the stomach include the cardia, fundus, body, antrum and the pylorus. Not only do these regions have specific secretory functions, but also, they have specific motor functions as well. For example, the proximal stomach is most important in regulating emptying of liquids and the distal stomach and pylorus, the emptying of solids. Disorders of gastric emptying can be classified into two major categories: mechanical obstruction due to increased resistance and functional obstruction (gastroparesis) due to pump failure. Gastroparesis is best diagnosed using a solid test meal which is labelled by a gammaemitting radionuclide. Agents employed to treat gastroparesis include bethanechol, metoclopramide and domperidone. Entero-gastric reflux occurs when there are abnormalities in the duodeno-gastric pressure gradient or the duodeno-gastric resistance mechanism. Excessive entero-gastric reflux may be seen in patients with gastric ulcers, chronic obstructive pulmonary disease, post-cholecys...
Mitigating the Risk of Coprecipitation of Pinacol during Isolation from Telescoped Miyaura Borylation and Suzuki Couplings Utilizing Boron Pinacol Esters: Use of Modeling for Process Design

Process definition and optimization of a telescoped Miyaura borylation and Suzuki coupling reaction employing bis(pinacolato)diboron (BisPin), used in the developmental synthesis of an intermediate for Abemaciclib, led to the unexpected coprecipitation of pinacol during the isolation. Thermodynamic phase separation, distillation, and pinacol phase diagram models were used to guide the design of a modified process to maintain pinacol fully soluble. A Quality by Design (QbD) approach was used to illustrate the control strategy and provide a maximally flexible process for manufacturing to maintain high purity of the intermediate. Different possible representations of the design space to mitigate pinacol precipitation are discussed and compared. The risk of pinacol precipitation may not be unique to the system of study and could have broad implication to the development of this class of reactions.
Empirically Based Strategies for Preventing Juvenile Delinquency

Juvenile crime is a serious public health problem that results in significant emotional and financial costs for victims and society. Using etiologic models as a guide, multiple interventions have been developed to target risk factors thought to perpetuate the emergence and persistence of delinquent behavior. Evidence suggests that the most effective interventions tend to have well-defined treatment protocols, focus on therapeutic approaches as opposed to external control techniques, and use multimodal cognitive-behavioral treatment strategies. Moving forward, there is a need to develop effective policies and procedures that promote the widespread adoption of evidence-based delinquency prevention practices across multiple settings.
Applying Statistical Causal Analyses to Agricultural Conservation: A Case Study Examining P Loss Impacts

Estimating the effect of agricultural conservation practices on reducing nutrient loss using observational data can be confounded by factors such as differing crop types and management practices. As we may not have the full knowledge of these confounding factors, conventional statistical meta-analysis methods can be misleading. We discuss the use of two statistical causal analysis methods for quantifying the effects of water and soil conservation practices in reducing P loss from agricultural fields. With the propensity score method, a subset of data was used to form a treatment group and a control group with similar distributions of confounding factors. With the multilevel modeling method, data were stratified based on important confounding factors, and the conservation practice effect was evaluated for each stratum. Both methods resulted in similar estimates of the conservation practice effect (total P load reduction avg. ~70%). In addition, both methods show evidence of conservation practices reducing the incremental increase in total P export per unit increase in fertilizer application. These results are presented as examples of the types of outcomes provided by statistical causal analyses, not to provide definitive estimates of P loss reduction. The enhanced meta-analysis methods presented within are applicable for improved assessment of agricultural practices and their effects and can be used for providing realistic parameter values for watershed-scale modeling.
Leveraging Resilience Evidence From the Management of Senior Low-Income Housing

Although public and private management approaches have been frequently analyzed for their outcomes along the lines of efficiency and equity, their relationship to fostering community resilience has been understudied. Public housing has undergone a market-based transition, devolving management and operations of its sites or tenants to private management companies. This multi-site case study evaluates different management contexts to understand how management processes encourage or discourage community resilience. Findings include that management can play an integral role in developing community resilience by providing spaces and opportunities for community engagement and resident empowerment. To better navigate in an era of austerity measures, this article recommends practitioners actively leverage and invest in citizen strengths to build more resilient programs.
Über die Gültigkeit des Pflüger'schen Gesetzes für die galvanotropischen Reaktionen von Paramaecium

1. Die Cilien ungereizter Paramaecien sind entweder in Ruhe oder ruckwartsschlagend. 2. Ein gereiztes Paramaecium fuhrt gewohnlich eine Reihe von Bewegungen aus, deren Hauptcharakteristikum in der Umkehr der Cilien besteht, so dass diese nun vorwarts schlagen. 3. Bei der Annahme der Umkehr der Cilien als Kriterium fur eine Reizung gilt Pfluger's Gesetz fur die Reizung der Cilien. Beim Schliessen und wahrend der Dauer des Stromes drehen sich die kathodalen — aber nur die kathodalen Cilien um und beim Offnen des Stromes die anodalen Cilien.
Interleukin-1β and interleukin-6 enhance thermal prolongation of the LCR in decerebrate piglets

Thermal stress and prior upper respiratory tract infection are risk factors for the Sudden Infant Death Syndrome. The adverse effects of prior infection are likely mediated by interleukin-1β (IL-1β). Therefore, we examined the single and combined effects of IL-1β and elevated body temperature on the duration of the Laryngeal Chemoreflex (LCR) in decerebrate neonatal piglets ranging in age from post-natal day (P) 3 to P7. We examined the effects of intraperitoneal (I.P.) injections of 0.3mg/Kg IL-1β with or without I.P. 10mg/Kg indomethacin pretreatment on the duration of the LCR, and in the same animals we also examined the duration of the LCR when body temperature was elevated approximately 2°C. We found that IL-1β significantly increased the duration of the LCR even when body temperature was held constant. There was a significant multiplicative effect when elevated body temperature was combined with IL-1β treatment: prolongation of the LCR was significantly greater than the sum of independent thermal and IL-1β-induced prolongations of the LCR. The effects of IL-1β, but not elevated body temperature, were blocked by pretreatment with indomethacin alone. We also tested the interaction between IL-6 given directly into the nucleus of the solitary tract (NTS) bilaterally in 100ngm microinjections of 50μL and pretreatment with indomethacin. Here again, there was a multiplicative effect of IL-6 treatment and elevated body temperature, which significantly prolonged the LCR. The effect of IL-6 on the LCR, but not elevated body temperature, was blocked by pretreatment with indomethacin. We conclude that cytokines interact with elevated body temperature, probably through direct thermal effects on TRPV1 receptors expressed pre-synaptically in the NTS and through cytokine-dependent sensitization of the TRPV1 receptor. This sensitization is likely initiated by cyclo-oxygenase-2 dependent synthesis of prostaglandin E2, which is stimulated by elevated levels of IL-1β or IL-6. Inflammatory sensitization of the LCR coupled with thermal prolongation of the LCR may increase the propensity for apnea and Sudden Infant Death Syndrome.
The Strategy of Multi-join Query Optimization of Database Based on Genetic Algorithm

In this paper,a strategy of query optimization,combined with characteristic of multi-join optimization,is proposed based on genetic algorithm.A model of genetic algorithm on state space of the left-deep tree of query strategy is constructed to optimize the multi-join operator.The method of chromosome coding on query optimization is showed,and further selection strategy,crossover and mutation of genetic algorithm are determined by the design of coding.
A survey on serological epidemiology of influenza A (H1N1) 2009 in Beijing

OBJECTIVE To investigate the immunological level against influenza A (H1N1) 2009 in Beijing and provide evidence to evaluate the developing trend of the disease. METHODS Between Nov. 27, 2009 and Dec. 23, 2009, subjects were randomly selected from patients in hospitals (infectious and respiratory diseases related departments were excluded), volunteers in blood donation center and healthy subjects attending the physical examination center. Questionnaire survey was conducted and serum samples were collected to detect the hemagglutination-inhibition (HI) antibody against influenza A (H1N1) 2009 virus. RESULTS 856 subjects participated in this survey, and 127 showed positive HI antibody to this pandemic virus. The proportions of sero-positivity among 0 - 5, 6 - 17, 18 - 55, ≥ 56 year olds were 14.5%, 19.4%, 17.4% and 8.0% respectively (P = 0.009). There was no significant difference in the sero-positivity between males and females (P = 0.693). The age-adjusted positive rate was 15.8% in the population of Beijing. By multivariate logistic regression analysis, factors as age, acute respiratory symptoms and the rate of pandemic (H1N1) 2009 vaccination were significantly associated with sero-positivity of HI antibody to the influenza A (H1N1) 2009 virus. CONCLUSION Above 15% of the population in Beijing showed protective antibody against influenza A (H1N1) 2009 virus, indicating the development of immunological barrier to this disease had been formed, to some extent.
Reliable Method for Detection of Programmed Cell Death in Yeast

Accumulating evidence suggests that yeasts are capable of undergoing programmed cell death (PCD) to benefit long-term survival of the species, and that yeast and mammals may share at least partially conserved PCD pathways. In our experience, mammalian apoptosis assays have not been readily applicable to yeast. Therefore, to take advantage of yeast as a genetic tool to study PCD, we developed a yeast cell death assay that can reliably reveal viability differences between wild-type strains and strains lacking the mitochondrial fission genes DNM1/Drp1 and FIS1, orthologs of mammalian cell death regulators. Cell viability following treatment with acetic acid is quantified by colony formation and vital dye (FUN1) staining to reproducibly detect dose-dependent, genetically programmed yeast cell death.
What Encourages Nonprofits' Adoption of Good Governance Policies?

This study examines how nonprofits' external environments and organizational characteristics explain their likelihood of having written policies for good governance. Findings from the 2010 data of the National Center for Charitable Statistics show that state requirements for registration and annual reporting are not related to a nonprofit's likelihood of adopting such written policies. The results instead indicate that organizations that engage in lobbying activities and operate in metropolitan areas are more likely to have good governance standards. Most of all, the analysis shows that organizational resources, both financial and human, explain differences in the adoption of these policies. These findings suggest that the nonprofit community should collectively invest in building the infrastructure that helps smaller organizations develop good governance policies and, hence, stay competitive.
Communicating Wave Energy: An Active Learning Experience for Students.

We have conducted an education project to communicate the wave energy concept to high school students. A virtual reality system that combines both hardware and software is developed in this project to simulate the buoy-wave interaction. This first-of-its-kind wave energy unit is portable and physics-based, allowing students to conduct a number of hands-on activities. This system is the core component of an educational experience that integrates demonstration and hands-on learning, with an aim of introducing the wave energy conversion process to students in an interactive environment. Presentations have been made at two different high schools with diverse student populations, and students involved in this project rated very positively about their learning experience. As revealed by their feedback, the virtual environment and its combination with the hardware are the most important factors that help students to appreciate the knowledge in the wave energy conversion process.
A “Walker” Tool to Place Diaphorina citri (Hemiptera: Liviidae) Adults at Predetermined Sites for Bioassays of Behavior in Citrus (Sapindales: Rutaceae) Trees

Summary A “walker” tool was developed to assist successful placement of Diaphorina citri Kuwayama (Hemiptera: Liviidae) adults at predetermined sites on citrus (Sapindales: Rutaceae) trees in behavioral bioassays. Use of the walker resulted in a significantly higher proportion of successful placements and a significantly lower number of jumps away from the predetermined site compared with the use of a brush, although on average it required an additional 108 s more than the 41 s required with the brush to complete a successful placement. Females and males performed similarly with both devices. Potentially, the walker is a useful placement tool under conditions where it is time and labor intensive to provide large numbers of insects with specific physiological characteristics for testing, e.g., when it is difficult to supply large numbers of D. citri adults of known sex, mating status, and age. Because phototaxis is commonly observed in psyllids, the walker may be of use also for bioassays with other econom...
Trends in the Incidence of Deep Vein Thrombosis and Pulmonary Embolism: A 35-Year Population-Based Study.

Abstract Background: Recent trends in the incidence of venous thromboembolism (VTE), including idiopathic vs. non-idiopathic VTE, have not been well described. Objective: To estimate the incidence of deep vein thrombosis (DVT) and pulmonary embolism with or without DVT (PE), and describe trends in incidence. Methods: Using the resources of the Rochester Epidemiology Project, we identified all Olmsted County, MN residents with an incident DVT and PE over the 35-year period, 1966–2000 (n=3342). For all cases, the complete medical records in the community were reviewed for demographic and baseline characteristics previously identified as risk factors for VTE. Generalized linear models assuming a Poisson error structure, and using a log link function, and a log (population) offset will be used to assess the relationship of crude incidence rates to gender, year of diagnosis and age at diagnosis. Results: The overall average age- and sex-adjusted annual VTE incidence was 122 per 100,000 person-years (DVT, 56 per 100,000; PE, 66 per 100,000), with higher age-adjusted rates among men than women (134 versus 115 per 100,000, respectively). VTE incidence rates increased exponentially with age for both genders, ranging from 4 to 1110 per 100,000 for age groups 0–19 to 90–110 years. Compared to the 5-year period, 1981–85 (when non-invasive diagnostic testing became routinely available), the overall VTE incidence through 2000 remains unchanged. However, the DVT incidence and the PE incidence significantly increased and decreased, respectively, adjusting for age and gender (p Conclusions: VTE remains a major national health problem, especially among the elderly. Despite improved VTE prophylaxis efficacy and utilization, the overall incidence of VTE remains unchanged. However, the decreasing incidence of idiopathic DVT, and particularly idiopathic PE (with its associated poor survival) raises the possibility that the total number of VTE(PE)-related deaths may also be decreasing, albeit slightly. This hypothesis requires formal testing. The increasing or steady incidence of non-idiopathic DVT and PE, respectively, suggests the need for more widespread, effective VTE prophylaxis.
Maize canopies under two soil water regimes. I. Diurnal patterns of energy balance, carbon dioxide flux, and canopy conductance

Abstract Photosynthesis of individual leaves and canopies in relation to transpiration has been studied fairly extensively with chambers, which, unfortunately, alter the environment of the plant. Scaling up remains a problem and there are only limited data on simultaneously measured water vapor and CO2 fluxes of crop canopies, especially comparing treatments grown side-by-side. In the present study, diurnal patterns of fluxes of CO2, latent heat, and other components of energy over adjacent fields of maize, one well watered and one growing only on water stored in the soil, were determined under clear and variable cloud conditions with the Bowen-ratio/energy balance/CO2 gradient (BREB+) technique. To follow the dynamic changes caused by weather conditions and to link them to canopy processes, averaging time of the signals was set for 5 min. Several lines of evidence validating this short averaging time are presented in the fourth paper of this series. Our data confirmed the known pivotal role of radiation in both latent heat (λE) and CO2 flux (Acf) of the canopy. Further, it was shown that the canopy responded to the movement of clouds without measurable lag, with Acf, λE and sensible heat (H) fluctuating in unison as the sun disappeared and reappeared. Acf, reaching peak values of about 30–35 μmol m−2 s−1, was higher in the morning than in the afternoon for the same level of Qp (photosynthetic photon flux density), and dropped to zero late in the afternoon when Qp was still substantial (e.g., 0.3 mmol m−2 s−1). This was apparently the result of increases in respiration as the temperature rose from the morning to the afternoon. Senescence of the canopy, whether normal as maturity was approached or accelerated by water stress, was associated with a general reduction in Acf for a given green leaf area index. Late in the life cycle, Acf was apparently light saturated at 1.3 to 1.6 mmol m−2 s−1. At that time, abnormally high radiation due to focusing by clouds caused an increase in λE and H, but not in Acf. Canopy conductances were calculated using the Penman–Monteith big leaf model after aerodynamic conductances were derived from wind data. The diurnal patterns showed that canopy conductance was strongly influenced by radiation, and was independent from and usually lower than aerodynamic conductances. Canopy conductance for water vapor reached noon-time values up to 40 mm s−1 under the most favorable water conditions. Water stress and senescence reduced canopy conductance. Aerodynamic conductance for water vapor ranged between 15 and 90 mm s−1 for wind velocity between 1 and 5 m s−1, respectively.
THE ISCHIAL SEAT BRACE

The substitute for the Thomas ring herein presented provides an easily adjustable ischial support which is comfortable and effective. It can be made by any competent bracemaker, and the expense to the patient should be not much more than that of the usual Thomas type of brace.
A method for correcting field strain measurements to account for temperature effects

Abstract Measurements of deformation and strain are of critical importance for the structural health monitoring of geosynthetic reinforced soil (GRS) structures. For some commonly used wiring configurations and sensors, field strain measurements can exhibit apparent strains that are caused by changes in wire temperature or changes in gauge temperature, which do not correspond to changes in actual strain in the geosynthetic. Correcting for these effects is important for separating out real structural behavior from wiring and sensor issues, and is imperative for avoiding false trigger warnings in automated instrumentation reporting systems. The current paper consequently presents a method for correcting field strain measurements to account for temperature effects. Data collected from sensors embedded in a heavily-instrumented GRS abutment over a two-year monitoring period is presented. The distributed thermistor array embedded in the GRS abutment is shown to be particularly useful for understanding temperature effects on the measured foil strain gauge data. The presented approach and associated framework for data correction are useful for practicing engineers and other researchers, as the general concepts from this study can be applied to data collected from many instrumented geosynthetic field projects.
HIF1α in aortic aneurysms and beyond.

Abdominal aortic aneurysm (AAA) is a permanent expansion of the vessel wall with a high prevalence in those 65 years of age and older. Aneurysms are prone to dissection and rupture that carry a mortality rate of over 85%. Currently, surgical repair is the only option to treat this disease. The need to intervene prior to these events has set off a flurry of basic studies in an effort to understand the cellular and molecular mechanisms that govern AAA formation, progression and rupture. In the present study, the role of myeloid cells in contributing to AAA development has been confirmed. More specifically, the transcription factor, hypoxia-inducible factor-1α (HIF1α), was demonstrated to be a necessary component for regulating the expression of extracellular matrix modifying enzymes and their endogenous inhibitors in these cells. This new discovery may lead to therapeutic targets to prohibit the degradation and weakening of the vessel wall with the hope of limiting AAA formation and/or growth.
Independent System Operators in The USA. History, Lessons Learned, and Prospects

Publisher Summary This chapter provides a cross-cutting perspective on the currently operating Independent System Operator (ISO) markets and the Federal Energy Regulatory Commission's broader public policy agenda. The design of the ISO markets is an evolutionary process in the USA as in most other countries. While many design experiments run, and some fail at high cost, there is increasing understanding of the relationship between design elements. Experience in ISO markets has led to a fair amount of consensus that the core design elements should include locational marginal pricing (LMP) of energy, a sequence of day-ahead (DA) and real-time (RT) markets, and financial transmission rights (FTRs). Moreover, artificial operational boundaries remain between ISOs, creating inefficiency, although there is great interest in coordination along with advances in metering and communication technology, paving the way to lower barriers to competition across large regions. While efficient pricing of marginal transmission usage over large regions is a significant achievement, there has been less satisfaction with the rules for FTRs, especially in establishing a relatively stable long-term hedge.
Wnt5a induces ROR1 to complex with HS1 to enhance migration of chronic lymphocytic leukemia cells

ROR1 (receptor tyrosine kinase-like orphan receptor 1) is a conserved, oncoembryonic surface antigen expressed in chronic lymphocytic leukemia (CLL). We found that ROR1 associates with hematopoietic-lineage-cell-specific protein 1 (HS1) in freshly isolated CLL cells or in CLL cells cultured with exogenous Wnt5a. Wnt5a also induced HS1 tyrosine phosphorylation, recruitment of ARHGEF1, activation of RhoA and enhanced chemokine-directed migration; such effects could be inhibited by cirmtuzumab, a humanized anti-ROR1 mAb. We generated truncated forms of ROR1 and found its extracellular cysteine-rich domain or kringle domain was necessary for Wnt5a-induced HS1 phosphorylation. Moreover, the cytoplamic, and more specifically the proline-rich domain (PRD), of ROR1 was required for it to associate with HS1 and allow for F-actin polymerization in response to Wnt5a. Accordingly, we introduced single amino acid substitutions of proline (P) to alanine (A) in the ROR1 PRD at positions 784, 808, 826, 841 or 850 in potential SH3-binding motifs. In contrast to wild-type ROR1, or other ROR1P→A mutants, ROR1P(841)A had impaired capacity to recruit HS1 and ARHGEF1 to ROR1 in response to Wnt5a. Moreover, Wnt5a could not induce cells expressing ROR1P(841)A to phosphorylate HS1 or activate ARHGEF1, and was unable to enhance CLL-cell motility. Collectively, these studies indicate HS1 plays an important role in ROR1-dependent Wnt5a-enhanced chemokine-directed leukemia-cell migration.
Pseudo-likelihood Estimation of Multidimensional Response Models: Polytomous and Dichotomous Items

Log-multiplicative association (LMA) models have been proposed as uni- and multidimensional item response models for dichotomous and/or polytomous items. A problem that prevents more widespread use of LMA models is that current estimation methods for moderate to large problems are computationally prohibitive. As a special case of a log-linear model, maximum likelihood estimation (MLE) of LMA models requires iteratively computing fitted values for all possible response patterns, the number of which increases exponentially as the number of items and/or response options per item increases. Anderson et al. (J. Stat. Softw. 20, 2007, doi:10.18637/jss.v020.i06) used pseudo-likelihood estimation for linear-by-linear models, which are special cases of LMA models, but in their proposal, the category scores are fixed to specific values. The solution presented here extends pseudo-likelihood estimation to more general LMA models where category scores are estimated. Our simulation studies show that parameter estimates from the new algorithm are nearly identical to parameter estimates from MLE, work for large numbers of items, are insensitive to starting values, and converge in a small number of iterations.
Geographic variation in opioid and heroin involved drug poisoning mortality rates

Introduction An important barrier to formulating effective policies to address the rapid rise in U.S. fatal overdoses is that the specific drugs involved are frequently not identified on death certificates. This analysis supplies improved estimates of state opioid and heroin involved drug fatality rates in 2014, and changes from 2008 to 2014. Methods Reported mortality rates were calculated directly from death certificates and compared to corrected rates that imputed drug involvement when no drug was specified. The analysis took place during 2016–2017. Results Nationally, corrected opioid and heroin involved mortality rates were 24% and 22% greater than reported rates. The differences varied across states, with particularly large effects in Pennsylvania, Indiana, and Louisiana. Growth in corrected opioid mortality rates, from 2008 to 2014, were virtually the same as reported increases (2.5 deaths per 100,000 people) whereas changes in corrected heroin death rates exceeded reported increases (2.7 vs 2.3 per 100,000). Without corrections, opioid mortality rate changes were considerably understated in Pennsylvania, Indiana, New Jersey, and Arizona, but dramatically overestimated in South Carolina, New Mexico, Ohio, Connecticut, Florida, and Kentucky. Increases in heroin death rates were understated in most states, and by large amounts in Pennsylvania, Indiana, New Jersey, Louisiana, and Alabama. Conclusions The correction procedures developed here supply a more accurate understanding of geographic differences in drug poisonings and supply important information to policymakers attempting to reduce or slow the increase in fatal drug overdoses.
Allergic rhinitis management: what’s next?

Introduction: Allergic rhinitis (AR) is characterized by the presence of congestion, postnasal drainage, sneezing and rhinorrhea. AR contributes to reduced productivity and significant morbidity wo...
Protected by a Fox

Cell-specific regulation of gene expression is important for maintaining cortical excitatory/inhibitory balance. In this issue of Neuron, Vuong et al. (2018) reveal an unlikely role for a broadly expressed RNA binding protein, Rbfox1, in protecting inhibitory transmission in the hippocampus.
Van der Waals Theory of Imperfect Gases

The essential difference between molecules that are “real,” and those that are postulated for the derivation of the ideal gas equation of state, is the following. Real molecules have finite size and they interact with each other. Ideal molecules are of zero size and have no interaction.
Contemplating the Meaning of 'Responsibility' in Responsible Command

Operating under responsible command is an essential requirement to qualify as a lawful combatant, and is also central to the criminal accountability doctrine of command responsibility. This reveals the indelible link between the role of the commander and the effective implementation of the law of armed conflict. Understanding this linkage is vital to ensuring that commanders and other military leaders fulfill their obligation to prepare subordinates to navigate the chaos of mortal combat within the legal, and by implication, moral framework the LOAC provides. Few commanders would question the proposition that responsible commanders prepare their military units to effectively perform their combat missions. However, operational effectiveness is only one aspect of developing a “responsible” command. Because this term is grounded in the expectation of LOAC compliance, a truly responsible command exists only when the unit is prepared to execute its operational mission in a manner that fully complies with LOAC obligations. This broader conception of a disciplined military unit reflects the true nature of the concept of responsible command, as only military units built on this conception of discipline advance the complementary objectives of military effectiveness and humanitarian respect. Accordingly, the requirement that lawful combatants operate under responsible command is an admonition to all military leaders that truly effective military units are those capable of executing their missions with maximum operational effect within the framework of humanitarian constraint that defines the limits of justifiable violence during armed conflict.
Patterns and Causes of Genetic Diversity in Arctic Plant

Low species diversity in arctic plant communities is low genetic diversity at one level. However, in this chapter I address the question of levels of within-species genetic variation in tundra plants. As studies in biogeography and physiological, population, community and ecosystem ecology typically ignore this level of variation, much less is known about within-species diversity than diversity of species in arctic and alpine (as well as other) communities. However, I will argue that in species-poor ecosystems such as tundra, within-species diversity may be as important as among-species diversity in terms of maintaining the integrity or persistence of tundra ecosystems in the face of climate change. Thus, studies of genetic variation in tundra plants may give important clues about the response of the entire ecosystem to environmental shifts.
Impact of comprehensive treatment for first episode psychosis on substance use outcomes: A randomized controlled trial.

Abstract Lifetime co-occurring substance use disorders are common at the time of presentation for treatment of a first episode of primary psychosis and persistent substance use disorder (SUD) leads to poorer outcomes. We assessed whether the NAVIGATE program, a coordinated specialty care service that includes optional substance abuse content reduced substance use compared to usual care in 404 individuals in the Recovery After Initial Schizophrenia Episode-Early Treatment Program (RAISE-ETP) study. Participants were randomized to two years of NAVIGATE (n = 223) or usual care (n = 181) and assessed monthly for substance use. At baseline, over one-half (51.7%) of the participants met criteria for a lifetime SUD, including over one-third with alcohol use disorder (36.4%) and with cannabis use disorder (34.7%). Contrary to our hypothesis, there was no treatment group by time interaction effect on days of self-reported substance use over the two-year follow-up. Participant exposure to the substance abuse component of the NAVIGATE program was low, suggesting that modifications to the program and training method for clinicians may be needed. Further research is needed to determine the most effective strategies for addressing substance use disorders in persons recovering from a first episode of psychosis.
Binning Based Data Reduction for Vector Field Data of a Particle-In-Cell Fusion Simulation

With this work, we explore the feasibility of using in situ data binning techniques to achieve significant data reductions for particle data, and study the associated errors for several post-hoc analysis techniques. We perform an application study in collaboration with fusion simulation scientists on data sets up to 489 GB per time step. We consider multiple ways to carry out the binning, and determine which techniques work the best for this simulation. With the best techniques we demonstrate reduction factors as large as 109x with low error percentage.
SemEval-2017 Task 12: Clinical TempEval

Clinical TempEval 2017 aimed to answer the question: how well do systems trained on annotated timelines for one medical condition (colon cancer) perform in predicting timelines on another medical condition (brain cancer)? Nine sub-tasks were included, covering problems in time expression identification, event expression identification and temporal relation identification. Participant systems were evaluated on clinical and pathology notes from Mayo Clinic cancer patients, annotated with an extension of TimeML for the clinical domain. 11 teams participated in the tasks, with the best systems achieving F1 scores above 0.55 for time expressions, above 0.70 for event expressions, and above 0.40 for temporal relations. Most tasks observed about a 20 point drop over Clinical TempEval 2016, where systems were trained and evaluated on the same domain (colon cancer).
Neo-Piagetian Theories of Cognitive Development

Abstract Neo-Piagetian theories of cognitive development emerged as attempts to preserve core theoretical and empirically supported aspects of Jean Piaget's seminal theory of intellectual development while addressing criticisms leveled against the theory. Neo-Piagetian theories preserve three basic ideas from Piaget's theory: (1) the unit of cognitive analysis is the scheme or psychological structure; (2) psychological structures undergo qualitative transformation over time; and (3) higher order structures develop through the differentiation and coordination of lower level structures. After a brief discussion of similarities and differences among prominent neo-Piagetian theories, one representative approach (dynamic skill theory) is discussed in depth. The discussion concludes with a description of recent advances in neo-Piagetian systems theory.
Influence of age at seizure onset on the acquisition of neurodevelopmental skills in an SCN8A cohort.

Objective To characterize a cohort of patients with SCN8A-related epilepsy and to perform analyses to identify correlations involving the acquisition of neurodevelopmental skills. Methods We analyzed patient data (n = 91) submitted to an online registry tailored to characteristics of children with SCN8A variants. Participants provided information on the history of their child's seizures, medications, comorbidities, and developmental skills based on the Denver II items. Spearman rank tests were utilized to test for correlations among a variety of aspects of seizures, medications, and neurodevelopmental progression. Results The 91 participants carried 71 missense variants (41 newly reported) and three truncating variants. Ages at seizure onset ranged from birth to >12 months of age (mean ± SD = 5 months 21 days ± 7 months 14 days). Multiple seizure types with multimodal onset times and developmental delay were observed as general features of this cohort. We found a positive correlation between a developmental score based upon percentage of acquired skills and the age at seizure onset, current seizure freedom, and initial febrile seizures. Analyses of cohort subgroups revealed clear distinctions between patients who had a single reported variant in SCN8A and those with an additional variant reported in a gene other than SCN8A, as well as between patients with different patterns of regression before and at seizure onset. Significance This is the first study of an SCN8A patient cohort of this size and for which correlations between age at seizure onset and neurodevelopment were investigated. Our correlation studies suggest that variants of uncertain significance should be considered in assessing children with SCN8A-related disorders. This study substantially improves the characterization of this patient population and our understanding of the neurodevelopmental effects associated with seizures for SCN8A patients, and provides a clinical context at initial presentation that may be prognostic for developmental outcome.
The Becoming of the Policy Maker

This essay explores the development of the term “policymaker” by reviewing major periodicals from 1870 until 1940, with particular focus upon the period of 1920 to 1940. Events of this period provi...
Evaluating sequence data quality from the Swift Accel-Amplicon CFTR Panel

Cystic fibrosis (CF) is one of the most common genetic diseases worldwide with high carrier frequencies across different ethnicities. Next generation sequencing of the cystic fibrosis transmembrane conductance regulator (CFTR) gene has proven to be an effective screening tool to determine carrier status with high detection rates. Here, we evaluate the performance of the Swift Biosciences Accel-Amplicon CFTR Capture Panel using CFTR-positive DNA samples. This assay is a one-day protocol that allows for one-tube reaction of 87 amplicons that span all coding regions, 5' and 3'UTR, as well as four intronic regions. In this study, we provide the FASTQ, BAM, and VCF files on seven unique CFTR-positive samples and one normal control sample (14 samples processed including repeated samples). This method generated sequencing data with high coverage and near 100% on-target reads. We found that coverage depth was correlated with the GC content of each exon. This dataset is instrumental for clinical laboratories that are evaluating this technology as part of their carrier screening program.
Synergistic effects of shear stress, moderate electric field, and nisin for the inactivation of Escherichia coli K12 and Listeria innocua in clear apple juice

Abstract Rotational shear stress (SS), moderate electric field (MEF), and nisin (NS) treatments were applied to study their effect on inactivation of Gram-negative (Escherichia coli K12) and Gram-positive (Listeria innocua) bacteria in clear apple juice. We evaluated the combined effects of shear rate (up to 2879 s−1) and MEF with a 60 Hz square-waveform and a duty cycle of 0.50–0.99, at 27 °C; followed by treatment with NS (0–100 IU/ml). The mechanisms of bacterial inactivation were investigated using plate counts and flow cytometry with SYTO-9/propidium iodide (PI) staining. Selected quality attributes (pH, color, and antioxidant activity) of juice samples were also evaluated. It was possible to achieve 5-log cycle reductions of both E. coli K12 and L. innocua, in samples treated for 5 min with SS at 2879 s−1 and MEF under a duty cycle of 0.99 in combination with NS treatment at 100 IU/ml without significant degradation in quality attributes when compared to the control. Flow cytometry results showed that the mechanism of cellular damage differed for E. coli K12 and L. innocua. In conclusion, the synergistic effects of the combination of SS+MEF with NS could represent a useful alternative to inactivate target pathogens in foods at temperatures below 30 °C.
95 – Radiation Arteriopathy

Publisher Summary This chapter describes various aspects of radiation arteriopathy. The histologic consequences of radiation upon normal tissue are dependent upon several factors, including tissue type, time interval after radiation, total dose, dose rate, the type of radiation, and other concurrent local factors which might influence a histologic response. Capillaries and sinusoids are the most radiosensitive of all vascular tissues, probably due to the extreme sensitivity of endothelium to ionizing radiation. Typical histological manifestations seen in capillaries and sinusoids after radiation include dilatation and talangiectasia, asymmetry in the capillary wall, prominent endothelial cells, and frequently thrombosis. The effect of radiation upon the development of delayed arterial narrowing has been inferred from a number of clinical features. Patients receiving radiation are often the same cohorts who are especially prone to atherosclerosis. Concurrent tumor, surgery, or infection is usually present in the irradiated field, all of which can lead to arterial narrowing. The potential mechanisms for radiation effect on arterial wall are also elaborated.
Fertility and Endocrine Preservation in the Management of Colorectal Cancer in Women.

CASE SUMMARY A 28-year-old nulliparous woman presented with rectal bleeding. Colonoscopy revealed a 4-cm malignant-appearing mass in the proximal rectum, and biopsies confirmed invasive adenocarcinoma of the rectum. Computed tomography scan showed no evidence of metastatic disease. Staging MRI found transmural extension with minimal stranding in the adjacent fat, as well as no evidence of pathological pelvic adenopathy, consistent with a T3N0 lesion. The proposed treatment plan involved neoadjuvant chemotherapy and radiation therapy before primary surgical resection. The patient desired fertility preservation and was referred immediately to Reproductive Endocrinology and Infertility. She underwent assisted reproduction with oocyte and blastocyst cryopreservation followed by laparoscopic ovarian transposition. Nine months after surgical low anterior resection of the tumor and completion of her cancer treatment, her ovaries were repositioned to their normal pelvic position during an ileostomy takedown procedure. She underwent a frozen embryo transfer but did not conceive. She resumed menses and later conceived spontaneously. Her pregnancy was complicated by cervical incompetence, requiring cervical cerclage. She delivered a live male infant via cesarean delivery at 32 weeks gestation, approximately 2 years after completion of cancer therapy. Four years after diagnosis, the patient remains in remission with undetectable CEA levels.