cssi/SciSciGPT-SciSciNet huggingface dataset:
Hematopoietic Stem Cells Are the Disease-Initiating Cells in the Myelodysplastic Syndromes

Abstract Abstract 789 Myelodysplastic syndrome (MDS) is a disorder of ineffective hematopoiesis presumed to originate from self-renewing clonal hematopoietic stem cells (HSC). Previous work has shown that immunophenotypic HSC from MDS patients harbor characteristic clonal cytogenetic abnormalities such as del(5q) at high levels, strongly suggesting that the HSC is the MDS-initiating cell (Tehranchi R., et al., NEJM, 363:11;1025-37, 2010); however, these studies did not examine other cytogenetic subtypes of MDS, nor did they functionally evaluate the HSC from these patients for their ability to initiate disease. We began a molecular and functional evaluation of FACS-purified HSC (Lin-CD34+CD38−CD90+CD45RA-) from MDS patients. These studies showed that the frequency of HSC in MDS bone marrow is not expanded when compared to normal, age-matched control samples. Annexin V staining also demonstrated no difference in apoptosis levels in MDS HSC compared to normal HSC; however, MDS committed myeloid progenitors (Lin-CD34+CD38+) exhibited increased apoptosis compared with normal progenitors (18% vs 39%, respectively, p 12 weeks) was achieved with 50% of MDS samples tested (4/8), and resulted predominantly in myeloid engraftment with 0.8–5% total hCD45+ chimerism in the bone marrow. For each MDS HSC engrafted mouse, engraftment of the MDS clone was verified by FISH by detecting previously characterized cytogenetic abnormalities in FACS-sorted hCD45+ cells. The frequency of FISH positive cells was similar to that seen in the primary samples, suggesting no competitive disadvantage of MDS HSC in the xenotransplantation assay. Interestingly, methylcellulose colony and clonal liquid culture assays initiated from FACS-purified MDS HSC consistently grew poorly, suggesting that in vitro assays of hematopoietic potential may not accurately reflect MDS HSC biology. Together, these studies indicate that while MDS HSC are molecularly and functionally different from normal HSC, they are capable of engrafting immunodeficient NSG pups. Moreover, these data formally demonstrate that the HSC is the disease-initiating cell in MDS. This finding has significant implications for MDS research, as it provides a potential in vivo preclinical model for testing MDS therapeutics – an experimental model previously not available to investigators. Disclosures: Schrier: Locus: Consultancy.
Dealing with Missing Values

A common task in data analysis is dealing with missing values. In R, missing values are often represented by NA or some other value that represents missing values (i.e. 99). We can easily work with missing values and in this chapter I illustrate how to test for, recode, and exclude missing values in your data.
Picking at Morals: Analytical Jurisprudence in the Age of Naturalized Ethics

Morality in analytical jurisprudence has always assumed a metaphysical and theoretical character. As morality and the law are connected in distinctive ways, morality plays a pivotal role in one’s understanding of the concept of law. Thus far, we have taken moral norms as providing a reliable measure of right and wrong actions. But the naturalization of ethics in moral philosophy has introduced research findings from the natural sciences which suggest that morality is far more nuanced and varied than we have come to assume. Some moral norms, evolutionary biology has shown us, have less to do with propriety, righteousness, or civility, and more to do with developed biological responses to our surrounding environment. Other moral norms emerged because of political reasons rather than rectitude. This paper argues that we should consider seriously these new findings about our moral psychology in the conceptualization of law in analytical jurisprudence. Morality, if it is an unreliable source of good conscience, cannot and should not be used to provide laws with the normative force it needs to justify the imposition of obligations or to govern with legitimate authority. Until neuroscientists and developmental psychologist are able to determine with some definiteness how our capacity for moral decisions functions and establish morality as a universal feature of humankind, we need to be cautious in how much faith we place on morality as a standard setting norm to separate right from wrong.
Significance: Statistical Versus Clinical

The conflation of statistical significance with clinical relevance is pervasive in the misrepresentation of research findings to the general public. Statistical significance is precisely defined as the likelihood that a difference or association between two groups was observed due to chance alone. After observing a statistically significant result, researchers should next assess the size of the difference or association, or the clinical significance of their finding. Generally, statistical significance is important to the scientific process, but clinical significance should play a larger role in medical decision-making. This chapter reviews statistical significance’s rise in popularity to the point of overreliance on this single metric, leading to the dubious practice known as p-hacking. Without measuring clinical significance or sufficient replication studies, false positive statistical anomalies can quickly become canon. When clinical significance results are published in the original study paper, media outlets rarely report this additional information. As such, the lay public rarely encounters information about the clinical significance of research findings.
Incorporating a pharmacist into an interprofessional team providing transgender care under a medical home model.

Purpose A pharmacist’s role in providing care to transgender and gender-nonconforming (TGNC) patients within a medical home model of care is described. Summary A comprehensive transgender services clinic was established in February 2015 in New Mexico. Clinic services are provided under an “informed consent” model of care, as opposed to the traditional “gatekeeper” approach. The clinic’s interprofessional team consists of a clinical pharmacist, a psychiatrist, a nurse practitioner, an endocrinologist, a diabetes educator, a massage therapist, a nurse, a nutritionist, and medical assistants. The clinical pharmacist has served in the following roles: (1) assessing health literacy and tailoring the consent process to the patient’s literacy level, (2) initiating in-depth discussion of the medical risks and benefits of cross-sex hormone therapy (HT), as well as HT alternatives, (3) discussing typical timelines for physical outcomes of HT, (4) discussing a patient’s expectations and goals for csHT, (5) discussing the different HT formulations and helping to determine which formulation is best suited to meeting patient’s goals, (6) helping the team obtain prior authorizations for csHT, and (7) managing risk reduction strategies such as smoking cessation and weight loss. Involvement of a pharmacist in the clinic has improved care access and quality for TGNC patients in the southwestern United States. Conclusion A pharmacist in an interprofessional team staffing a clinic for TGNC people has assumed multiple responsibilities and helped improve patient care.
Diabetes status modifies the association between carotid intima-media thickness and incident heart failure: The Atherosclerosis Risk in Communities study

Abstract Aims Increasing carotid intima-media thickness (CIMT) is associated with incident heart failure (HF). We investigated whether this association differs by diabetes status. Methods We characterized 13,590 Atherosclerosis Risk in Communities Study participants free of baseline HF into normal fasting glucose (NFG, glucose Results T2D participants had higher mean CIMT (0.79 ± 0.20 mm), compared to IFG (0.75 ± 0.19 mm) and NFG (0.70 ± 0.17 mm) (p Conclusions CIMT is associated with increased risk of HF, particularly among persons without diabetes. Due to a high absolute risk of HF among adults with T2D, CIMT may be a less reliable predictor.
Docosahexaenoic acid blocks progression of western diet-induced nonalcoholic steatohepatitis in obese Ldlr-/- mice.

Background Nonalcoholic fatty liver disease (NAFLD) is a major public health concern in western societies. Nonalcoholic steatohepatitis (NASH), the progressive form of NAFLD, is characterized by hepatic steatosis, inflammation, oxidative stress and fibrosis. NASH is a risk factor for cirrhosis and hepatocellular carcinoma. NASH is predicted to be the leading cause of liver transplants by 2020. Despite this growing public health concern, there remain no Food and Drug Administration (FDA) approved NASH treatments. Using Ldlr -/- mice as a preclinical model of western diet (WD)-induced NASH, we previously established that dietary supplementation with docosahexaenoic acid (DHA, 22:6,ω3) attenuated WD-induced NASH in a prevention study. Herein, we evaluated the capacity of DHA supplementation of the WD and a low fat diet to fully reverse NASH in mice with pre-existing disease. Methods Ldlr -/- mice fed the WD for 22 wks developed metabolic syndrome (MetS) and a severe NASH phenotype, including obesity, dyslipidemia, hyperglycemia, hepatic steatosis, inflammation, fibrosis and low hepatic polyunsaturated fatty acid (PUFA) content. These mice were randomized to 5 groups: a baseline group (WDB, sacrificed at 22 wks) and 4 treatments: 1) WD + olive oil (WDO); 2) WD + DHA (WDD); 3) returned to chow + olive oil (WDChO); or 4) returned to chow + DHA (WDChD). The four treatment groups were maintained on their respective diets for 8 wks. An additional group was maintained on standard laboratory chow (Reference Diet, RD) for the 30-wk duration of the study. Results When compared to the WDB group, the WDO group displayed increased hepatic expression of genes linked to inflammation (Opn, Il1rn, Gdf15), hepatic fibrosis (collagen staining, Col1A1, Thbs2, Lox) reflecting disease progression. Mice in the WDD group, in contrast, had increased hepatic C20-22 ω3 PUFA and no evidence of NASH progression. MetS and NASH markers in the WDChO or WDChD groups were significantly attenuated and marginally different from the RD group, reflecting disease remission. Conclusion While these studies establish that DHA supplementation of the WD blocks WD-induced NASH progression, DHA alone does not promote full remission of diet-induced MetS or NASH.
The Role of Positive Inotropic Drugs in the Treatment of Older Adults with Heart Failure and Reduced Ejection Fraction

Positive inotropic drugs have long been studied for their potential benefits in patients with heart failure and reduced ejection fraction (HFrEF). Although there has been an extensive amount of research about the clinical effects of these drugs in general, few studies examined their effect in older patients. Therefore, there is little or no evidence to guide the use of positive inotropes in older patients with HFrEF. However, recommendations from national heart failure guidelines may be generalized to older HFrEF patients on an individual basis, taking into consideration the basic geriatric principles of pharmacotherapy: start low and go slow.
I Use the Student Recreation Center, but I Would Use it More if …: Understanding Male and Female Constraints to Student Recreation Center Use:

Studies have found that there is a positive relationship between the number of student visits to campus recreation and academic outcomes such as rates of graduation and grade point average (Huesman...
Three-Dimensional Geoscience Modeling and Simulation of Gas Explosion in Coal Mine

Gas explosion is one of the most serious events in coal mine. In consideration of the limitation of past research method about gas explosion, three-dimensional (3D) modeling and simulation are suggested. This paper analyzes the research achievements on 3D modeling, and studies the modeling method of strata and laneway based on geoscience modeling. After the 3D modeling of strata and laneways, the simulation of gas explosion (such as gas exploding, color, burning, virtual wandering and rock caving) is performed. The research method is meaningful for safety analysis and safety survey.
Recurrent Pectus Excavatum Repair

Recurrent pectus excavatum is more challenging to repair than primary pectus excavatum and requires significant knowledge of the risks and pitfalls in these complex repairs, as well as experience with the advantages and disadvantages of the various techniques available. This chapter will review types of recurrence and selection of open or closed technique in re-do repair, as well as preoperative preparation and technical considerations for repair of recurrent excavatum.
Long-Run Relation among Motor-Fuel Use, Vehicle Miles Travelled, Income, and Gas Price for the US

Energy used in transport is a particularly important focus for environment-development studies since such use is increasing in both developed and developing countries and is a carbon-intensive activity everywhere. Gasoline price and per capita motor fuel consumption (and therefore CO2 emissions) are highly correlated, but it may be too simplistic to assume that higher prices will lead to lower use and thus emissions since there may be a systemic relationship among price, technology, and mobility demand. This paper examines whether a systemic, cointegrated relationship exists among gasoline price, income, and both per capita motor fuel consumption and per capita vehicle-miles traveled, using US yearly data from 1919-2004 and the Johansen cointegration test. The paper’s finding of a cointegrating relationship means that gasoline price, technology, and fuel consumption cannot be easily disentangled in the short-run. JEL classification: Q43
Application of UGT1A1 Genetic Testing in Patients Treated with Irinotecan

PL07-03 Application of UGT1A1 genetic testing in patients treated with irinotecan Federico Innocenti, MD, PhD University of Chicago, Department of Medicine, Section of Hematology-Oncology, 5841 S. Maryland Avenue, MC2115, Chicago, IL 60637; business telephone: 773-834-2452; fax: 773-702-9698; email: finnocen@medicine.bsd.uchicago.edu Abstract Irinotecan is widely used in the treatment of metastatic colorectal cancer and extensive small-cell lung cancer. Its use is limited by severe toxicities, such as neutropenia and delayed-type diarrhea. The pharmacology of irinotecan is quite complex. Irinotecan is converted to its active metabolite SN-38. SN-38 is further metabolized to SN-38G by various hepatic and extrahepatic UGT1A isozymes, mainly UGT1A1. Genetically impaired glucuronidation activity of the UGT1A1 enzyme has been linked with elevated levels of SN-38. UGT1A1*28 is the most studied functional UGT1A1 variant and involves an extra TA repeat in the UGT1A1 promoter region. In several studies, homozygosity for the UGT1A1*28 allele has been associated with a higher risk of severe toxicity of irinotecan in cancer patients. This wealth of information led to the revision of the irinotecan label by the FDA. Recently, in addition to the UGT1A1*28 allele, the UGT1A1*6 variant seems to contribute to the risk of toxicity of irinotecan in Asian patients. The pharmacogenetics of irinotecan (irinogenetics) is one of few promising examples of the application of pharmacogenetics to individualized drug therapy. This talk will discuss the use of UGT1A1 genetic testing for avoiding severe toxicity of irinotecan in predisposed patients. In addition, genotype-directed trials of irinotecan will be discussed, as an example of tailored dosing in oncology that could be obtained by knowing the genetic make up of patients.
Likelihood ratio order of parallel systems under multiple-outlier models

ABSTRACTThis paper studies the likelihood ratio ordering of parallel systems under multiple-outlier models. We introduce a partial order, the so-called θ-order, and show that the θ-order between th...
Brain amyloid PET interpretation approaches: from visual assessment in the clinic to quantitative pharmacokinetic modeling

Cerebral β-amyloid burden can be measured by positron emission tomography (PET) tracers, including 11C-Pittsburgh Compound B (11C-PiB) and three fluorinated tracers that have been approved by regulatory agencies. This review focuses on the current clinical use of amyloid PET and the added utility of quantifying β-amyloid deposition. Using systematic review methods, a PubMed search identified studies on the added value of standardized uptake value ratio (SUVR) to visual reads. PubMed search was also performed to identify studies that illustrate important factors that cause variability in SUVR results, as well as key papers in the initial development of 11C-PiB. Among studies comparing visual interpretation and SUVR, there is high concordance between visual reads and SUVR for diagnosis classification, with evidence that SUVR decreases inter-reader variability in visual interpretation and improves accuracy. The variability among results of studies utilizing SUVR is likely multifactorial, including choice of reference regions, choice of target regions, and methods for determining SUVR thresholds. The initial 11C-PiB studies illustrate the importance of rigorous pharmacokinetic modeling and stepwise simpler quantitative methods when translating radiotracers. There is increasing evidence of the added value of SUVR in the clinic, in particular in borderline cases or for detection of subtle changes. SUVR provides a reasonably accurate measurement of amyloid plaque deposition compared to pharmacokinetic modeling methods.
Stress‐Generative Effects of Posttraumatic Stress Disorder: Transactional Associations Between Posttraumatic Stress Disorder and Stressful Life Events in a Longitudinal Sample

Longitudinal studies have demonstrated transactional associations between psychopathology and stressful life events (SLEs), such that psychopathology predicts the occurrence of new SLEs, and SLEs in turn predict increasing symptom severity. The association between posttraumatic stress disorder (PTSD), specifically, and stress generation remains unclear. This study used temporally sequenced data from 116 veterans (87.9% male) to examine whether PTSD symptoms predicted new onset SLEs, and if these SLEs were associated with subsequent PTSD severity. The SLEs were objectively rated, using a clinician-administered interview and consensus-rating approach, to assess the severity, frequency, and personal dependence (i.e., if the event was due to factors that were independent of or dependent on the individual) of new-onset SLEs. A series of mediation models were tested, and results provided evidence for moderated mediation whereby baseline PTSD severity robustly predicted personally dependent SLEs, B = 0.03, p = .006, and dependent SLEs predicted increases in follow-up PTSD symptom severity, B = -0.04, p = .003, among participants with relatively lower baseline PTSD severity. After we controlled for baseline PTSD severity, personality traits marked by low constraint (i.e., high impulsivity) were also associated with an increased number of dependent SLEs. Our results provide evidence for a stress-generative role of PTSD and highlight the importance of developing interventions aimed at reducing the occurrence of personally dependent stressors.
Oxidation of Water to Molecular Oxygen

Numerous papers have been published on the topic of water oxidation; however, the light-driven water splitting enzyme still remains one of the enigmas of photosynthesis. In this chapter, we have summarized the advances made on the oxidation of H2O to O2 The water-oxidizing complex includes, at least, the reaction center proteins D1 and D2 and a 33 kilodalton extrinsic protein; other proteins seem also to be involved. The 33 kDa extrinsic protein may turn out to be dispensable for the molecular mechanism of O2 evolution. Chloride and calcium ions are also required, although their exact functions remain unknown. It is clear, however, that Mn undergoes dynamic changes as the oxygen clock moves from relaxed states So to S1 and S1 to S2 This is followed by conversion of S2 to S3 and S3 to S4 until O2 is evolved. It is accepted that Mn is the charge accumulator, but it is considered likely now that at one of the steps, a histidine residue may act as a redox active ligand, and store the charge. It was generally believed that Ih are released as 1,0, 1,2 during So → S1,S1 → S2 S2 → S3 and S3 → (S4) → So transitions. However, the currently accepted pattern is 1,0.5, I and 1.5. The nature of the intermediates of water oxidation form H20 to O2 is still unknown. Although the recent knowledge about the 3-D crystal structure of the reaction center complex from purple photosynthetic bacteria has led to a more precise picture of a portion of the water oxidizing complex than known before, further understanding will come after this complex is crystallized and its 3-D structure known and after rnethods are evolved to trap and monitor transient intermediates in water oxidation.
Stress analysis of an infinite plate containing an elastic rectangular inclusion

A solution is presented for determining the stresses in an infinite elastic plate containing an elastic rectangular inclusion subjected to a uniform stress field. The bond stresses are obtained by treating the plate and the inclusion separately and satisfying continuity of displacements at discrete points rather than continuously. An example of a square elastic inclusion is treated in detail. Comparison is made between the solution obtained by point-matching techniques and the exact solution for a rigid square inclusion. Excellent agreement is observed. The practical motivation behind this research was the estimation of the bond stresses induced between the fibers and matrix of multifiber composite sheets.
[Arg 16 ]chicken secretin

[Arg16]chicken secretin was synthesized with the aim of producing a selective vasoactive intestinal polypeptide (VPAC-1) receptor agonist with a decreased affinity for secretin receptors …
Toxicity of PD-1/CTLA-4 inhibitor immunotherapy among elderly patients.

e14139Background: The use of Immune check point inhibitors in advanced metastatic melanoma is becoming increasingly common especially in the elderly population. With metastatic melanoma being mostl...
The key role of representativeness in evidence-based education

ABSTRACTWithin evidence-based education, results from randomised controlled trials (RCTs), and meta-analyses of them, are taken as reliable evidence for effectiveness – they speak to “what works”. ...
Alpha herpesvirus egress and spread from neurons uses constitutive secretory mechanisms independent of neuronal firing activity

Abstract Alpha herpesviruses naturally infect the peripheral nervous system, and can spread to the central nervous system causing severe deadly or debilitating disease. Because alpha herpesviruses spread along synaptic circuits, and infected neurons exhibit altered electrophysiology and increased spontaneous firing, we hypothesized that alpha herpesviruses use activity-dependent synaptic vesicle-like regulated secretory mechanisms for egress and spread from neurons. To address this hypothesis, we used a compartmentalized primary neuron culture system to measure egress and spread of pseudorabies virus (PRV), pharmacological and optogenetics approaches to modulate neuronal firing activity, and a live-cell fluorescence microscopy assay to directly visualize the exocytosis of individual virus particles from infected neurons. Using tetrodotoxin to silence neuronal activity, we observed no inhibition of virus spread, and using potassium chloride or optogenetics to elevate neuronal activity, we also show no increase in virus spread. Using a live-cell fluorescence microscopy method to directly measure virus egress from infected neurons, we observed no association between virus particle exocytosis and intracellular Ca2+ signaling. Finally, we observed virus particle exocytosis occurs in association with constitutive secretory Rab GTPases, Rab6a and Rab8a, not Rab proteins that are associated with the Ca2+-regulated secretory pathway in neurons, Rab3a and Rab11a. Therefore, we conclude that alpha herpesvirus egress and spread is independent of neuronal activity and Ca2+ signaling because virus particle exocytosis uses constitutive secretory mechanisms in neurons. Author Summary Alpha herpesviruses, including important human pathogens Herpes Simplex Virus 1 and 2, and Varicella-Zoster Virus, are among the very few viruses that naturally infect the nervous system. These viruses cause recurrent herpetic and zosteriform lesions, peripheral neuropathies, and deadly or debilitating central nervous system diseases. Many of the molecular and cellular mechanisms of viral egress and spread remain unknown, particularly in the context of specialized neuronal cell biology. Our results indicate that elevated firing activity of infected neurons is not functionally or mechanistically linked to virus egress and spread; therefore, therapies targeting peripheral neuropathic symptoms, elevated neuronal activity, and synaptic vesicle secretory mechanisms are unlikely to affect virus spread in the nervous system.
CO2 reduction with protons and electrons at a boron-based reaction center

Borohydrides are widely used reducing agents in chemical synthesis and have emerging energy applications as hydrogen storage materials and reagents for the reduction of CO2. Unfortunately, the high energy cost associated with the multistep preparation of borohydrides starting from alkali metals precludes large scale implementation of these latter uses. One potential solution to this issue is the direct synthesis of borohydrides from the protonation of reduced boron compounds. We herein report reactions of the redox series [Au(B2P2)] n (n = +1, 0, -1) (B2P2, 9,10-bis(2-(diisopropylphosphino)phenyl)-9,10-dihydroboranthrene) and their conversion into corresponding mono- and diborohydride complexes. Crucially, the monoborohydride can be accessed via protonation of [Au(B2P2)]-, a masked borane dianion equivalent accessible at relatively mild potentials (-2.05 V vs. Fc/Fc+). This species reduces CO2 to produce the corresponding formate complex. Cleavage of the formate complex can be achieved by reduction (ca. -1.7 V vs. Fc/Fc+) or by the addition of electrophiles including H+. Additionally, direct reaction of [Au(B2P2)]- with CO2 results in reductive disproportion to release CO and generate a carbonate complex. Together, these reactions constitute a synthetic cycle for CO2 reduction at a boron-based reaction center that proceeds through a B-H unit generated via protonation of a reduced borane with weak organic acids.
Phonological contrastivity in conversation: a comparative study of voice onset time

Abstract: Voice onset time (VOT) characteristics were examined in the speech of three adult females under the following conditions: (1) adultdirected conversation; (2) child-directed conversation; and (3) recitation of citation forms. VOT values were derived from frequency-by-time wide and narrow band spectrograms. A categorical classification system was designed to describe variant occurrences of stop productions in conversational speech. Results indicate that there are significant differences between citational forms and conversational speech in both the total percent of measurable stops as well as in the VOT values themselves. Overall, there were no significant differences between adult-directed and child-directed conversation; however, a few individual speaker differences were noted. The results are discussed in terms of physiological variables as well as current theories concerning parental roles in the infants’ acquisition of language.
How action on climate change could benefit United States natural gas producers, but not without federal mandates

Stimulated by a properly designed carbon tax, the United States natural gas (NG) industry could produce and consume more NG than business as usual (BAU) while staying within the emission level goal of the 2015 United Nations Climate Change Conference (COP21) to avoid exceeding an average +2°C global temperature rise. Explored are two options for the United States petroleum industry for lowering carbon emissions 80% by 2050. One option examines voluntary reduction in emissions and the other uses a United States federal carbon tax to diminish coal usage and incentivize carbon capture and storage. Also examined are economic implications for the industry following BAU with an average global temperature rise of approximately 2°C by 2050. By correlating drops in United States petroleum consumption and production with declines in global gross domestic product during the Great Recession of 2008–2009, projections are made for economic declines modeled by Burke et al. (2015) coinciding with BAU warming. Consumption of NG and oil in the United States suffered minor decreases from 2008 to 2009, but production levels did not. This indicates economic repercussions to United States petroleum caused by global warming are minor compared to the 80% drop needed to meet the COP21 goal. It is unlikely the United States petroleum industry will suffer major economic losses following a BAU path, discounting the potential costs of disasters and international or political conflicts resulting from climate change. Because of the range of potential positive to negative impacts resulting from climate change, however, the membership of AAPG should debate how to address this issue.
Machine Learning and Predicted Returns for Event Studies in Securities Litigation Preliminary and Incomplete

We investigate the use of machine learning (ML) and other robust-estimation techniques in event studies conducted on single securities for the purpose of securities litigation. Single-firm event studies are widely used in civil litigation, with billions of dollars in settlements hinging on the outcome of the exercise. We find that regularization (equivalently, penalized estimation) can yield noticeable improvements in both the variance of event-date abnormal returns and significance-test power. Thus we believe that there is a role for ML methods in event studies used in securities litigation. At the same time, we find that ML-induced performance improvements are smaller than those based on other good practices. Most important are (i) the use of a peer index based on returns for firms in similar industries (how this is computed appears to be less important than that some version be included), and (ii) for significance testing, using the SQ test proposed in Gelbach, Helland, and Klick (2013), because it is robust to the considerable non-normality present in abnormal returns.
Shp1 in Solid Cancers and Their Therapy

Shp1 is a cytosolic tyrosine phosphatase that regulates a broad range of cellular functions and targets, modulating the flow of information from the cell membrane to the nucleus. While initially studied in the hematopoietic system, research conducted over the past years has expanded our understanding of the biological role of Shp1 to other tissues, proposing it as a novel tumor suppressor gene functionally involved in different hallmarks of cancer. The main mechanism by which Shp1 curbs cancer development and progression is the ability to attenuate and/or terminate signaling pathways controlling cell proliferation, survival, migration, and invasion. Thus, alterations in Shp1 function or expression can contribute to several human diseases, particularly cancer. In cancer cells, Shp1 activity can indeed be affected by mutations or epigenetic silencing that cause failure of Shp1-mediated homeostatic maintenance. This review will discuss the current knowledge of the cellular functions controlled by Shp1 in non-hematopoietic tissues and solid tumors, the mechanisms that regulate Shp1 expression, the role of its mutation/expression status in cancer and its value as potential target for cancer treatment. In addition, we report information gathered from the public available data from The Cancer Genome Atlas (TCGA) database on Shp1 genomic alterations and correlation with survival in solid cancers patients.
Robotic Bronchoscopy for the Diagnosis of Peripheral Lung Nodules: a Review

Conventional bronchoscopy has limitations based on an inability to accurately reach and reliably diagnose peripheral lesions with many studies having a yield of less than 50%. Although newer technology such as virtual bronchoscopy, use of smaller bronchoscopes, peripheral endobronchial ultrasound, and electromagnetic navigation may have some improvements and a better safety profile, oftentimes transthoracic or surgical biopsies are required to establish a diagnosis and rule out malignancy. The purpose of this review is to highlight the potential benefits of robotic bronchoscopy, the latest in technological advances for this very common medical issue. Recently published early studies suggest the yield of robotic bronchoscopy may surpass 90%. Studies performed in cadavers and humans suggest robotic bronchoscopic platforms are better than currently existing bronchoscopic modalities for lung nodule diagnosis and have a favorable safety profile. Although additional multi-center randomized clinical trials are needed, robotic bronchoscopy appears poised to supplement current bronchoscopic techniques for establishing a diagnosis of pulmonary nodules.
Comprehensive Geriatric Assessment

Comprehensive geriatric assessment (CGA) is a multidisciplinary or interdisciplinary approach that is tailored to the older adult. Domains addressed included physical and mental health, prevention, function, and quality of life, achieved in conjunction with addressing environmental factors and patient safety. CGA is tailored to the stage of life, in the overall context of health status and life expectancy. Attention is paid to psychosocial issues, implementation of advance directives, medication review and reconciliation, and caregiver support and burden. Current practice guidelines address several disorders common in the old, but tend to differ based on the source, requiring providers to tailor recommendations to the individual’s health status and preferences.
Using Political Event Derivatives to Illustrate the Binomial Option Pricing Model

When students first learn about the binomial option pricing model (BOPM), the idea of modeling a stock price distribution with a binomial tree can appear abstract. In this paper, we present a simple way to illustrate the BOPM to a scenario that is a true binomial event, an election result. Using the quoted prices on the Iowa Electronic Market (IEM) for election futures contracts, synthetic options can be created and priced using the BOPM. This exercise provides the opportunity to illustrate to students how an option on a binomial event is the same as a futures contract on the same event.
Voltage Collapse Stabilization in Star DC Networks

Voltage collapse is a type of blackout-inducing dynamic instability that occurs when power demand exceeds the maximum power that can be transferred through a network. The traditional (preventive) approach to avoid voltage collapse is based on ensuring that the network never reaches its maximum capacity. However, such an approach leads to inefficient use of network resources and does not account for unforeseen events. To overcome this limitation, this paper seeks to initiate the study of voltage collapse stabilization, i.e., the design of load controllers aimed at stabilizing the point of voltage collapse. We formulate the problem of voltage stability for a star direct current network as a dynamic problem where each load seeks to achieve a constant power consumption by updating its conductance as the voltage changes. We introduce a voltage collapse stabilization controller and show that the high-voltage equilibrium is stabilized. More importantly, we are able to achieve proportional load shedding under extreme loading conditions. We further highlight the key features of our controller using numerical illustrations.
Corticosteroid Treatment of Healthy Early-lactation Dairy Cows

Effects of isoflupredone acetate and dexamethasone were studied in 68 healthy Holstein dairy cows. Cows in a single herd were screened for health status on day 4 or 5 after calving, then randomly assigned to receive 1)20 mg isoflupredone acetate on day 0: 2) 20 mg isoflupredone acetate on day 0 and day 1: 3) 20 mg dexamethasone on day 0: or 4)10 cc normal saline on day 0.
“Natural” Food Claims: Industry Practices, Consumer Expectations, and Class Action Lawsuits

This article examines industry practices, consumer expectations, and class action lawsuits involving natural food claims. Although anecdotal evidence of disputes regarding natural claims is plentiful, there have been few comprehensive, quantitative analyses. This article adds to this debate. It presents data on food manufacturer and retailer use of natural claims, and consumer perceptions of natural claims for food products during the timeframe 2010–2014. It then identifies 22 purported class action lawsuits alleging false or misleading natural claims on food labels and details the causes of action underlying each claim. Insofar as a gap remains between firm use and consumer expectations, regulators and lawmakers should set clear parameters on use of natural claims on food labels.
Performance Evaluation for Secure Communications in Mobile Internet of Vehicles With Joint Reactive Jamming and Eavesdropping Attacks

Internet of Vehicles (IoV) is considered to be a backbone of smart transportation system where vehicles are expected to exchange traffic information and other data using vehicle-to-vehicle (V2V) communications. Furthermore, V2V communications is regarded as a medium to send upcoming traffic information to vehicles/drivers or passengers using wireless technology in a timely manner. This will help reduce traffic accidents, traffic jams, fuel consumption caused by traffic jams, loss of hours caused by delayed commuting and carbon emission caused by vehicles. Because of the critical nature of IoV for smart transportation systems, secure wireless communication is one of the critical and essential components to offer trustworthy services through IoV. Like in other wireless systems, wireless communication is open in air, which makes attackers' job easy to launch the malicious actions in IoV. In this paper, we investigate the impact of mobility of vehicles for secure communications in IoV with joint jamming and eavesdropping attacks. We investigate different scenarios, when vehicles (legitimate ones and attackers) travel in same and opposite directions with low speed (school zone speed) limit to highway speed limit. Furthermore, we study the impact of association time and encryption time not only for establishing the connection between vehicles for V2V communications but also for exchanging messages for vehicles after successful association between vehicles and encryption of the message. In addition, we also study the joint impact of jamming and eavesdropping attacks in IoV for different speed limits, transmission ranges and wireless bandwidths. We investigate the extra cost in terms of transmit power and bandwidth incurred by jamming and eavesdropping attacks while maintaining the same secrecy rate as it could have been without those attacks. Numerical results are used to support the analysis.
Henoch-Schönlein Purpura Presenting as a Rash and Proteinuria in a 59-Year-Old Woman.

Henoch-Schonlein purpura is a disease of unknown etiology. it is predominantly seen in children, although adults are also affected, and comprises a rash, arthritis, abdominal pain, and renal dysfunction. there is no effective treatment, although the syndrome is self-limiting and generally subsides without sequelae. The authors present a case of Henoch-Schonlein purpura in a 59-year-old woman who presented with a rash of six months' duration and a high level of urinary protein.
The Effects of Type of Pronouns and Hope Appeals in Supportive Messages About COVID-19:

This study examined the role of pronouns in supportive messages and hope appeals in facilitating people's coping with coronavirus 2019 (COVID-19). Participants included 256 residents of New York St...
Data Citation Index: Promoting attribution, use and discovery of research data

The Data Citation Index forms part of the Thomson Reuters Web of Science research platform. Thomson Reuters makes partnerships with data repositories to create indexed data object metadata records integrated within the larger platform. The core features of the Data Citation Index strengthen and standardize citation and re-use of data across scientific disciplines.
Word equations with length constraints: what's decidable?

We prove several decidability and undecidability results for the satisfiability and validity problems for languages that can express solutions to word equations with length constraints. The atomic formulas over this language are equality over string terms (word equations), linear inequality over the length function (length constraints), and membership in regular sets. These questions are important in logic, program analysis, and formal verification. Variants of these questions have been studied for many decades by mathematicians. More recently, practical satisfiability procedures (aka SMT solvers) for these formulas have become increasingly important in the context of security analysis for string-manipulating programs such as web applications. We prove three main theorems. First, we give a new proof of undecidability for the validity problem for the set of sentences written as a ∀∃ quantifier alternation applied to positive word equations. A corollary of this undecidability result is that this set is undecidable even with sentences with at most two occurrences of a string variable. Second, we consider Boolean combinations of quantifier-free formulas constructed out of word equations and length constraints. We show that if word equations can be converted to a solved form, a form relevant in practice, then the satisfiability problem for Boolean combinations of word equations and length constraints is decidable. Third, we show that the satisfiability problem for quantifier-free formulas over word equations in regular solved form, length constraints, and the membership predicate over regular expressions is also decidable.
Flipping the History Classroom with an Embedded Writing Consultant: Synthesizing Inverted and WAC Paradigms in a University History Survey Course

“Flipping” the Classroom techniques and the use of Embedded Writing Consultants (EWC) in institutions of higher education have been the subject of scholarly research in recent years. However, it appears that no studies have examined the simultaneous use of both “tools” in an introductory History course at the university level. This essay examines the instructor's efforts to concurrently implement Flipping strategies and EWC assistance in a single course and student perceptions of these tools. The data used to analyze this process may assist other instructors who are considering or already using Flipping techniques or EWCs in their courses.
Attributes for Executing Change in an Agile Information System

Information Systems IS agility is a current topic of interest in the IS industry. The study follows up on work on the definition of the construct of IS agility and attributes for sensing and diagnosis in an agile IS. IS agility is defined as the ability of an IS to sense a change in real time; diagnose it in real time; and select and execute an action in real time. This paper explores the attributes for selecting and executing a response in an Agile Information System. A set of attributes were initially derived using the practitioner literature and then refined using interviews with practitioners. The attributes' importance and validity was established using a survey of the industry. All attributes derived in this study were deemed pertinent for selecting and executing a change in an agile information system. Dimensions underlying these attributes were identified using Exploratory Factor Analysis. This list of attributes can form the basis for assessing and establishing execution mechanisms to increase IS Agility.
Persistent cerebrospinal fluid otorrhea: a case of Munchausen's syndrome by proxy

A case is presented of a young child who initially presented with recurrent bacterial meningitis 1 year after significant head trauma and was found to have cerebrospinal fluid (CSF) leakage into the middle ear. Surgical procedures were devised to attempt to stop this abnormal flow, but inexplicably clear otorrhea biochemically identical to CSF persisted for weeks. The child's mother was apparently soaking the surgical dressings with CSF obtained through a lumbar drain and confessed to this activity after she was found to have tampered with an intravenous catheter. This activity resulted in a prolonged hospital stay and several presumably unnecessary procedures. Munchausen's syndrome, typified by intentional mimicry of symptoms of serious illness backed by plausible medical history, is well-described. Rarer is the syndrome by proxy, where parents and/or caregivers, by falsifying histories, fabricating laboratory evidence, or deliberately generating bodily lesions, cause unneeded diagnostic and therapeutic procedures to be performed on their young victims. This form of child abuse is hidden by the perpetrator's apparent concern and involvement in the care of the victim. The literature is reviewed, this form of abuse is discussed, and the role of communication of suspicion between the various health care workers is stressed. The medical and social settings in which this disorder is prevalent are covered. Early detection of this entity is essential in rescuing the victim from life-threatening abuse and in obtaining appropriate therapy for the abuser.
Injectable extracellular matrix derived hydrogel provides a platform for enhanced retention and delivery of a heparin-binding growth factor

Injectable hydrogels derived from the extracellular matrix (ECM) of decellularized tissues have recently emerged as scaffolds for tissue-engineering applications. Here, we introduce the potential for using a decellularized ECM-derived hydrogel for the improved delivery of heparin-binding growth factors. Immobilization of growth factors on a scaffold has been shown to increase their stability and activity. This can be done via chemical crosslinking, covalent bonding, or by incorporating natural or synthetic growth factor-binding domains similar to those found in vivo in sulfated glycosaminoglycans (GAGs). Many decellularized ECM-derived hydrogels retain native sulfated GAGs, and these materials may therefore provide an excellent delivery platform for heparin-binding growth factors. In this study, the sulfated GAG content of an ECM hydrogel derived from decellularized pericardial ECM was confirmed by Fourier transform infrared spectroscopy and its ability to bind basic fibroblast growth factor (bFGF) was established. Delivery in the pericardial matrix hydrogel increased retention of bFGF both in vitro and in vivo in ischemic myocardium compared to delivery in collagen. In a rodent infarct model, intramyocardial injection of bFGF in pericardial matrix enhanced neovascularization by approximately 112% compared to delivery in collagen. Importantly, the newly formed vasculature was anastomosed with existing vasculature. Thus, the sulfated GAG content of the decellularized ECM hydrogel provides a platform for incorporation of heparin-binding growth factors for prolonged retention and delivery.