cssi/SciSciGPT-SciSciNet huggingface dataset:
Journal Club Standardization Tool: Helping participants get the JIST.

Abstract Background and purpose Clinical pharmacy practice relies on the ability to critically evaluate clinical trials and apply their findings to patient care. The development of these skills begins in pharmacy school, develops during residency programs, and continues to mature while practicing clinical pharmacy. The purpose of this analysis was to evaluate student attitudes and perceptions following implementation of the Journal Interpretation Summary Tool (JIST) into a pharmacy curriculum. Educational activity and setting The “journal club” is an activity implemented in many curricula with the intent to hone these skills. The JIST is a standardized template aimed at improving the consistency of a journal review by organizing major elements of a trial, allowing the facilitator and participants to navigate through key information and guide the journal club discussion. Findings Implementation of JIST resulted in an increased level of confidence for a majority of students (63.3%) when conducting and critically evaluating a journal article. More than 80% of students reported they were better able to critically evaluate a published article using JIST, and 91.9% reported JIST provided structure to the journal club process. Discussion and summary JIST provides the appropriate level of guidance and structure, particularly for the novice pharmacy student or pharmacist. The use of a standardized tool for journal club evaluation may lead to further improvements in applying literature to practice and other skills surrounding the critique of medical literature.
At the intersection of self and not-self: finding the locus of ‘self’ in autoimmunity

Individuals with chronic autoimmune disease experience a sense of vulnerability. In part, this relates to the struggle for finding the meaning of the illness. The consequent existential distress may manifest in an unseated sense of personhood. Insight into the mechanism of this state of powerlessness and of perceived loss of agency is central to establishing a supportive clinician–patient relationship. This present exposition underscores the concept of autoimmunity as one that represents a demarcation in the psyche: one that is not just a threat to our sense of self-hood but also to our humanity. Autoimmunity exposes the challenge imposed on the relating of the self to one’s own self and hence is an ontological challenge. The breach of the boundary between self and not-self that is caused by the autoimmune process culminates in feelings of alienation.
Asymptotic Expansion of Integrals

The analysis of differential and difference equations in Chaps. 3 to 5 is pure local analysis; there we predict the behavior of solutions near one point, but we do not incorporate initial-value or boundary-value data at other points. As a result, our predictions of the local behavior usually contain unknown constants. However, when the differential or difference equation is soluble, we can use the boundary and initial data to make parameter-free predictions of local behavior.
Arbitrage-free Pricing in User-based Markets

Users have various attributes, and in user-based markets there are buyers who wish to buy a target set of users with specific sets of attributes. The problem we address is that, given a set of demand from the buyers, how to allocate users to buyers, and how to price the transactions. This problem arises in online advertising, and is particularly relevant in advertising in social platforms like Facebook, LinkedIn and others where users are represented with many attributes, and advertisers are buyers with specific targets. This problem also arises more generally in selling data about online users, in a variety of data markets. We introduce \em arbitrage-free pricing, that is, pricing that prevents buyers from acquiring a lower unit price for their true target by strategically choosing substitute targets and combining them suitably. We show that \em uniform pricing -- pricing where all the targets have identical price -- can be computed in polynomial time, and while this is arbitrage-free, it is also a logarithmic approximation to the maximum revenue arbitrage-free pricing solution. We also design a different arbitrage-free non-uniform pricing -- pricing where different targets have different prices -- solution which has the same guarantee as the arbitrage-free uniform pricing but is empirically more effective as we show through experiments. We also study more general versions of this problem and present hardness and approximation results.
Growth and Cellular Characteristics of Multicell Spheroids

Experience with culture methods for multicell spheroids has demonstrated the importance of optimizing and standardizing the growth conditions for different cell types and research objectives. Spheroid growth kinetics, cellular properties, and microenvironmental characteristics are significantly influenced by spheroid cellular metabolism and the macroenvironmental conditions during the culture period. These conditions include constituents of the culture medium, frequency of replenishment of the medium, the oxygen and glucose concentrations and geometric and convection properties in the culture flask.
Relationship Between Antiproliferative Activities and Class I MHC Surface Expression of Mouse Interferon Proteins on B16-F10 Melanoma Cells

Interferons (IFN) are a related family of cytokines that display potent antiviral and antiproliferative activities. In humans, there are at least 17 distinct type I IFNs including 13 distinct IFN-α proteins along with a single functional beta (IFN-β), epsilon (IFN-e), kappa (IFN-κ), and omega (IFN-ω) protein. Moreover, IFN-α subtype proteins induce the expression of hundreds of individual genes in a cell- and stimulus-dependent manner. Also, the individual IFN-α subtype proteins have been shown to differentially regulate the activity of B, T, natural killer, and dendritic cells. Consequently, it is possible that certain IFN-α subtypes (or combinations) can produce improved direct antitumor activity and possibly modify effector cells of the immune system directing an immune response against tumor cells resulting in clearance of cancer. The use of IFN-α2 has been highly successful in treating several distinct cancers that initially included hairy cell leukemia that has expanded to include chronic myelogenous leukemia and cutaneous T-cell lymphoma. In addition, it has also been indicated for the post-surgical treatment of malignant melanoma (MM) to limit cancer recurrence.
Time in Therapeutic Tacrolimus Range Predicts 1-Year Clinical Rejection and Survival: Time For a Paradigm Shift?

Purpose Calcineurin inhibitors are a cornerstone of immunosuppression post-orthotopic heart transplantation (OHT). The relationship of tacrolimus exposure, measured by time within therapeutic range (TTR), and level variability, measured by standard deviation (SD) of trough blood levels, to post-OHT acute rejection is unclear. We evaluated if tacrolimus TTR or variability in the 1-year post OHT impacted rejection. Methods This was a single-center, retrospective cohort study of consecutive adult OHT patients receiving standard immunosuppression with tacrolimus, MMF, and prednisone. Tacrolimus TTR was calculated up to 1 year using protocol goal ranges (10-15 ng/mL for months 0-2, 8-12 ng/mL for months 2-6 and 5-10 ng/mL for months 6-12) using the Rosendaal method. The primary outcomes included the association of TTR and level variability with 1-year clinical rejection (defined as any patient receiving ≥ 125 mg of IV methylprednisolone from post-op day 7-365). We analyzed categorical and continuous variables using chi-square and Mann Whitney-U respectively. Time-to-event analysis was conducted for 1-yr clinical rejection using both Kaplan-Meier and Cox Proportional Hazards methods, whereby TTR was calculated until event or censor date and reported using hazard ratio (HR) and 95% confidence interval (CI). Results 78 patients underwent OHT (age, 56.2 ± 12.7 years) with a median 1-yr TTR of 50.2%. Clinical rejection occurred in 31 (39.7%) patients. Those with clinical rejection had a significantly lower median TTR (45.9%) and higher level variability (5.8) than those without rejection (TTR 56.5%, variability 4.9; p=0.021 and p=0.005, respectively) (Figure A&B) . Time to therapeutic tacrolimus level (median 9 days) did not predict 1-year clinical rejection (p=0.274). In a univariable Cox Proportional Hazards Model (median TTR=40%), TTR Figure C ). Five (6.4%) patients died in the first year after OHT. TTR 50% (p=0.018, Figure D ). Conclusions Lower tacrolimus TTR and/or greater level variability predicts clinical rejection and death in the first year after OHT. TTR and and level variability should be monitored in addition absolute levels.
Gender Differences in Authorship in the Journal of Cardiothoracic and Vascular Anesthesia: A 28-Year Analysis of Publications Originating From the United States, 1990-2017.

Objective Gender-based differences in scholarship among cardiothoracic anesthesiologists have not been studied. The authors examined the gender distribution of authorship of original research articles, case reports, review articles, and editorials in the Journal of Cardiothoracic and Vascular Anesthesia (JCVA) originating from the United States during four 3-year intervals to determine temporal changes in productivity of women in cardiothoracic anesthesiology. The authors tested the hypothesis that scholarly output of women has increased progressively in JCVA over time concomitant with greater participation in first, last, and corresponding author roles. Design Observational study. Setting Internet analysis. Participants Authors of research articles, case reports, review articles, and editorials published in JCVA in 1990-92, 1999-2001, 2008-10, and 2015-17. Interventions None. Measurements and Main Results The gender of each author was determined by inspection of the first name. If gender could not be established easily, the author's institutional website was examined or an internet search using the Google search engine was conducted. First, last, and corresponding authors as well as coauthors were noted for each article. A total of 1,195 publications with 4,982 authors (1,032 women; 20.7%) were examined. Gender was identified positively in 98.5% of authors. Women were first, last, and corresponding authors on 22.4%, 10.3%, and 14.6% of publications, respectively. The percentage of women who were authors increased from 12.1% in 1990-92 to 20.9% in 1999-2001 (p Conclusion The results indicate that scholarly output of women rose in JCVA over time, but gains in productivity have plateaued more recently. These findings are encouraging, but women continue to be underrepresented in corresponding and last author roles.
Lateralized Suppression of Alpha-Band EEG Activity As a Mechanism of Target Processing.

Alpha-band (8–12 Hz) EEG activity has been linked to visual attention since the earliest EEG studies. More recent studies using spatial cuing paradigms have shown that alpha is suppressed over the hemisphere contralateral to a to-be-attended location, suggesting that alpha serves as a mechanism of preparatory attention. Here, we demonstrate that alpha also plays a role in active target processing. EEG activity was recorded from a group of healthy male and female human subjects in two visual search experiments. In addition to alpha activity, we also assessed the N2pc event-related potential component, a lateralized transient EEG response that has been tightly linked with the focusing of attention on visual targets. We found that the visual search targets triggered both an N2pc component and a suppression of alpha-band activity that was greatest over the hemisphere contralateral to the target (which we call “target-elicited lateralized alpha suppression” or TELAS). In Experiment 1, both N2pc and TELAS were observed for targets presented in the lower visual field but were absent for upper-field targets. However, these two lateralized effects had different time courses and they responded differently to manipulations of crowding in Experiment 2. These results indicate that lateralized alpha-band activity is involved in active target processing and is not solely a preparatory mechanism and also that TELAS and N2pc reflect a related but separable neural mechanism of visuospatial attention. SIGNIFICANCE STATEMENT The very first EEG studies demonstrated that alpha-band (8–12 Hz) EEG oscillations are suppressed when people attend to visual information and more recent research has shown that cuing an individual to expect a target at a specific location produces lateralized suppression in the contralateral hemisphere. Therefore, lateralized alpha may serve as a preparatory mechanism. In the present study, we found that a similar lateralized alpha effect is triggered by the appearance of a visual target even though the location could not be anticipated, demonstrating that alpha also serves as an active mechanism of target processing. Moreover, we found that alpha lateralization can be dissociated from other lateralized measures of target selection, indicating that it reflects a distinct mechanism of attention.
Efficiency in Programming for Generalization: Comparison of Two Methods for Teaching Expressive Labeling to Preschoolers with Developmental Delays

An adapted alternating treatments design was used to compare the efficiency of two methods of programming for generalization. Four preschool subjects with developmental delays were taught expressive identification of object pictures. During Condition I, single exemplars for each of two objects were trained to acquisition successively until generalization criterion was met. During Condition II, five exemplars for each of two objects were trained concurrently until generalization criterion was attained. Efficiency was measured by comparing the following sets of data for each treatment condition: (a) number of trials/training sessions through acquisition and generalization criteria, (b) rate of errors during acquisition, and (c) total instructional time through generalization criterion. Overall, data indicate that training exemplars concurrently resulted in both faster acquisition and generalization, although the total percentage of errors was greater.
In the Wake of Discovery: Student Perceptions, Integration, and Instructional Design

AbstractAcademic libraries have increasingly adopted web-scale discovery tools in order to meet the expectations of students who want immediate results, efficient algorithms, and a single search box. As they have become the de facto search tool at many libraries, librarians and patrons alike have been forced to confront the way they think about research processes and in some cases, modulate ingrained habits. In this article, the authors explore student perceptions of efficacy, relevancy, and ease of use of a library discovery tool through a 2017 mixed-methods user experience study conducted at three City University of New York (CUNY) campuses. The results from this user study will be useful to other institutions that already have implemented discovery layers within their library and help inform website design, discovery layer design, and pedagogy. By combining student interviews with a task analysis, the authors were able to learn more about student search behaviors, how they respond to challenges, and wh...
Methylation and Silencing of miRNA-124 In Hematopoietic Cells by EVI1

Abstract Abstract 2476 The inappropriate expression of EVI1 is associated with aggressive myelodysplastic syndromes (MDS) and acute myeloid leukemia. We previously showed that in vivo EVI1 causes an MDS-like disease in mice and that in vitro it alters cell cycling, self-renewal, and differentiation pathways of primary bone marrow (BM) cells. It is likely that these alterations contribute to the oncogenic potential of EVI1. MicroRNAs (miRNA) are small noncoding RNAs that are 21 to 25 nt in length that up- and down-regulate gene expression during cell development, proliferation, differentiation, and apoptosis. MiRNAs play a critical role in solid and hematopoietic cancers. We found that in hematopoietic cells the expression of several miRNAs is significantly altered by EVI1. Among them, miRNA-124 is strongly downregulated in EVI1-expressing primary BM and 32Dcl3 cells. To evaluate the role of miRNA-124 in primary murine BM cells, we isolated Lin- cells and infected the cells with the empty vector, EVI1, or both EVI1 and miRNA-124. We confirmed that EVI1 alters cellular pathways regulating self-renewal, S1 phase entry, and differentiation. More importantly, however, we found that when miRNA-124 is co-expressed with EVI1, the expression of proteins such as Cyclin D3 and BMI-1, that control some of these pathways, is normalized. These results suggest that the effects of EVI1 are mediated by miRNA-124 repression. We hypothesized that the down-regulation of miRNA-124 could be associated with inappropriate DNA methylation of the miRNA. Both in man and mouse, there are three known alleles of miRNA-124. In the mouse, the alleles are located on chromosome bands 2H4, 3A1, and 14D1. Analysis of the three alleles indicates that miRNA-124-3 harbors the larger number of CpG dinucleotides, including 24 CpG within a stretch of 190 bp upstream of and overlapping the stem-loop start-site. By using the bisulfite DNA sequencing method, we found that in BM cells the number of methylated CpG dinucleotides in this region is significantly increased after EVI1 expression. The DNA methylation is mostly centered in two clusters, which we named cluster I and cluster II. These data clearly show that miRNA-124 is a critical target of EVI1 in human diseases. Disclosures: No relevant conflicts of interest to declare.
C-MYC Rearrangement: A Marker for High-Risk Myeloma

Abstract Abstract 4989 Background: The proto-oncogene c-MYC encodes a transcription factor that regulates cell proliferation, growth, and apoptosis. c-MYC is mapped to the 8q24. 1 on the long arm of chromosome 8 and its rearrangement has been reported in 15% of myeloma patients independent of the disease stage (Avet-Loiseau et al. Blood 2001). However, the clinical significance of c-MYC rearrangement is not well described. Here we report the characteristics and outcome of myeloma patients with c-MYC rearrangements that were treated at our institution. Methods: We identified 18 patients (11 males, 7 females) with c-MYCrearrangements either on fluorescence in situ hybridization (FISH) analyses or conventional cytogenetics, who were treated at the M.D. Anderson Cancer Center. The primary objective was to describe the patient characteristics, response to therapy, time to progression (TTP), and overall survival (OS). Results: Median age at diagnosis was 56. 5 years (21–72). Overall, 8 patients (44%) presented with or progressed to either plasma cell leukemia (PCL: 6) or plasmablastic myeloma (PBM: 2). Abnormalities involving chromosome 8q24. 1, the c-MYC locus, were detected on conventional cytogenetics in all 18 patients, including t(8;14)(q24. 1;q32) in 6 cases, t(2;8)(p12;q24. 1) in 3 cases, t(8;22) (q24. 1;q11. 2) in 4 cases, t(8;20)(q24. 1;q13. 3) in one case, and an abnormal chromosome 8 with unknown material attached to the 8q24. 1 region in 4 cases. Five patients (27%) had a del(13)(q14. 1)/RB1, one of whom had a del(17)(p13)/TP53, while 3 other patients had t(11;14)(q13;q32) involving CCND1-XT/IGHrearrangements. Twelve patents (66%) received induction with a novel agent: bortezomib-based = 8 (44%) and thalidomide- based = 4 (22%). Six patients (33%) received induction with conventional chemotherapy regimens: CVAD (cyclophosphamide, vincristine, doxorubicin and dexamethasone) = 2, pulsed steroids only = 2, EPOCH (Etoposide, doxorubicin, vincristine, prednisone, cyclophosphamide) = 1 and melphalan + prednisone =1. Nine patients achieved a partial response (PR, 50%) and 4 patients achieved a very good partial remission (VGPR, 22%), with an overall response rate of 72% to induction. Thirteen patients (72%) went on to receive high-dose chemotherapy and autologous hematopoietic stem cell transplantation (auto-HCT). Four patients died of disease progression before auto-HCT while one patient opted for stem cell harvest and cryopreservation only. Median time to auto-HCT was 7. 1 months (3. 6–12. 7). Median follow up in all patients was 13 months (range 3. 4–105). Fifteen patients had progressed, with a median TTP of 7. 1 months and a median OS of 20. 2 months. Patients with PCL or PBM had significantly shorter OS (p=0. 04). Conclusion: This is the first report describing clinical characteristics of myeloma patients with c-MYC rearrangements. c-MYC rearrangement is associated with a higher incidence of plasma cell leukemia or plasmablastic myeloma, short TTP and OS. Disclosures: No relevant conflicts of interest to declare.
The Zebrafish Hypochromic Mutant [iItalic]Shiraz[/iItalic] Encodes a Novel Mitochondrial Glutaredoxin That Establishes a Link between Heme and Fe/S Production.

Iron is required in the mitochondria both to produce heme, which is used for hemoglobin synthesis, and to make iron-sulfur (Fe/S) clusters, which confer electron transfer or catalytic functions to proteins. Cellular iron utilization and Fe/S cluster production are thought to occur independently, yet the processes are coordinated through currently uncharacterized pathways. The shiraz (sir) zebrafish mutant manifests a hypochromic, microcytic anemia. Positional cloning of sir discovered a deletion at the locus that included the zebrafish orthologue to glutaredoxin 5 (grx5), a gene required in yeast for Fe/S cluster assembly. We found that grx5 is highly expressed in the developing blood and fetal liver of both zebrafish and mouse embryos. Antisense-mediated morpholino knockdown of grx5 prevented hemoglobin production, and overexpression of zebrafish, yeast, mouse, or human grx5 RNA in sir embryos completely rescued hemoglobin production, indicating that grx5 is the gene responsible for the sir phenotype. Expression of zebrafish grx5 was found to rescue Fe/S protein production in the yeast Δgrx5 strain, demonstrating that the role of grx5 in Fe/S cluster assembly is conserved among eukaryotes. The surprising finding that mutating a gene necessary for Fe/S cluster assembly caused a lack of hemoglobin synthesis suggested that we had discovered a connection between these pathways. In vertebrates, iron regulatory protein 1 (IRP1) acts as a sensor of intracellular iron levels and controls cellular iron homeostasis via posttranscriptional regulation of iron uptake, storage, and utilization genes. For instance, IRP1 binds to the 5′ iron response element (IRE) in the aminolevulinate synthase 2 (ALAS2) mRNA, blocking translation when cellular iron is low. However, when cellular iron is replete, IRP1 binds a Fe/S cluster and its RNA-binding activity is abolished. We hypothesized that the loss of Fe/S cluster assembly in sir would activate IRP1 and block ALAS2 synthesis, resulting in hypochromia. In support of this model, overexpression of ALAS2 RNA without the 5′ IRE rescued sir hypochromia, while overexpression of ALAS2 including the IRE did not facilitate rescue. Furthermore, antisense morpholino knockdowns of IRP1 caused rescue of hemoglobin synthesis in sir embryos. The combination of these data indicate that hemoglobin production in the differentiating red cell is monitored through Fe-S cluster assembly as a mechanism to gauge iron levels and accordingly direct heme synthesis. This finding illustrates a crucial role for the mitochondrial Fe/S cluster assembly machinery during hemoglobin production, and has broad implications for the role of such genes in human hypochromic anemias.
Spectroscopic investigation of supramolecular organometallic compound L-threonine cadmium acetate monohydrate.

Abstract Single crystal of L-Threonine cadmium acetate monohydrate, a supramolecular compounds crystallized by evaporation technique. The coordination network exhibit interesting structural property and have been investigated by Powder and single crystal X-ray diffraction. The functional group was identified using FTIR analysis. Dielectric property in a metal organic frame network plays an important role in the use of solid state as bioelectrical materials for various tissue engineering applications due to its relative permittivity. The UVVis studies suggested that UV absorption ability might be used as a corrosion resistant semiconductor material for optical device fabrication system. The non linear optical efficiency predicts that the material possesses good absorption coefficient.
Mechanism-Specific Pharmacodynamics of a Novel Complex-I Inhibitor Quantified by Imaging Reversal of Consumptive Hypoxia with [18F]FAZA PET In Vivo

Tumors lack a well-regulated vascular supply of O2 and often fail to balance O2 supply and demand. Net O2 tension within many tumors may not only depend on O2 delivery but also depend strongly on O2 demand. Thus, tumor O2 consumption rates may influence tumor hypoxia up to true anoxia. Recent reports have shown that many human tumors in vivo depend primarily on oxidative phosphorylation (OxPhos), not glycolysis, for energy generation, providing a driver for consumptive hypoxia and an exploitable vulnerability. In this regard, IACS-010759 is a novel high affinity inhibitor of OxPhos targeting mitochondrial complex-I that has recently completed a Phase-I clinical trial in leukemia. However, in solid tumors, the effective translation of OxPhos inhibitors requires methods to monitor pharmacodynamics in vivo. Herein, 18F-fluoroazomycin arabinoside ([18F]FAZA), a 2-nitroimidazole-based hypoxia PET imaging agent, was combined with a rigorous test-retest imaging method for non-invasive quantification of the reversal of consumptive hypoxia in vivo as a mechanism-specific pharmacodynamic (PD) biomarker of target engagement for IACS-010759. Neither cell death nor loss of perfusion could account for the IACS-010759-induced decrease in [18F]FAZA retention. Notably, in an OxPhos-reliant melanoma tumor, a titration curve using [18F]FAZA PET retention in vivo yielded an IC50 for IACS-010759 (1.4 mg/kg) equivalent to analysis ex vivo. Pilot [18F]FAZA PET scans of a patient with grade IV glioblastoma yielded highly reproducible, high-contrast images of hypoxia in vivo as validated by CA-IX and GLUT-1 IHC ex vivo. Thus, [18F]FAZA PET imaging provided direct evidence for the presence of consumptive hypoxia in vivo, the capacity for targeted reversal of consumptive hypoxia through the inhibition of OxPhos, and a highly-coupled mechanism-specific PD biomarker ready for translation.
Examining the effectiveness of measuring team brand association networks with textual analysis software

As brand associations are a key component of team brand equity, and ultimately influence consumer behaviour, it is important to have accurate measures of these associations. Previous research has developed scales to measure team brand associations, yet it has been suggested that pre-existing scales may not capture salient features of brands and any unique brand associations not captured by scaled measures. In addition, scales will not uncover the brand association networks and how team brand associations are interconnected. However, with advances in technology there is potential to develop methods which accomplish these goals. This study utilises a freethought listing technique to capture team brand associations which were then analysed by the Leximancer textual analysis software. The results suggest that this method provides an avenue to more accurately uncover the most salient team brand associations and to visualise team brand association networks.
Diabetic Kidney Disease

Diabetic kidney disease (DKD) continues to be a chronic and devastating complication of diabetes. Despite improvements in glycemic control and lower blood pressure targets, the incidence of DKD has not declined substantially. Standards of care for persons with diabetes include screening for kidney complications and close follow-up. Preventive measures continue to rely on glucose and blood pressure control. However, additional measures to slow the progression of kidney damage are under investigation.
Economic Aspects of Energy Storage

To many, the subject of economics means cost comparison. Indeed, a thorough understanding of costs is the prerequisite to understanding other economic issues. However, economics extends beyond costs. There are historical, political, and cultural aspects of all economic issues; I do not intend to address these here. In addition, there is another fundamentally important aspect of economics. Economics is, or should be, a theory of economic activity. The most outstanding feature of economic activity, since about the end of the 14th century, has been rapid, incessant change: change in the techniques of production, accompanied by consequent change in economic and political institutions and in the everyday lives of all human beings. Economic theory, as it now stands, can deal pretty well with trade. However, economics is weak in its capacities to deal with technical change. Indeed it was only recently that the Nobel committee awarded the prize to Robert Solow for his pioneering work showing the importance of technical change in the growth of economic output and productivity.
Monitoring Gas Exchange

Critical illness can threaten the adequacy of O2 delivery or CO2 excretion. Monitoring seeks to identify the adequacy of oxygenation and ventilation and to detect deterioration early. Advances in oximetry, capnography, and transcutaneous CO2 monitoring offer new opportunities for more accurate estimation of gas exchange, noninvasive monitoring of parameters previously not amenable (eg, total hemoglobin measurement), detection of disease, and prediction of fluid responsiveness.
Associations Between Depressive Symptoms and HFpEF-Related Outcomes

Abstract Objectives This study analyzed changes in depressive symptoms in patients with heart failure and preserved ejection fraction (HFpEF) who were enrolled in the TOPCAT (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function) trial. Background There are limited longitudinal data for depressive symptoms in patients with HFpEF. Methods In patients enrolled in the United States and Canada (n = 1,431), depressive symptoms were measured using Patient Health Questionnaire-9 (PHQ-9). Clinically meaningful changes in PHQ-9 scores were defined as worse (≥3-point increase) or better (≥3-point decrease). Multivariate models were used to identify predictors of change in depressive symptoms. Cox proportional hazard models were used to determine the impact of symptom changes from baseline on subsequent incident cardiovascular events. Results At 12 months, 19% of patients experienced clinically worsening depressive symptoms, 31% better, and 49% unchanged. Independent predictors of clinically meaningful improvement in depressive symptoms included higher baseline PHQ-9 scores, male sex, lack of chronic obstructive pulmonary disease, and randomization to spironolactone. After data were adjusted for cardiovascular comorbidities, higher baseline PHQ-9 was associated with all-cause mortality (hazard ratio [HR]: 1.09; 95% confidence interval [CI]: 1.02 to 1.16; p = 0.011), whereas worsening depressive symptoms at 12 months were associated with cardiovascular death (HR: 2.47; 95% CI: 1.32 to 4.63; p = 0.005) and all-cause mortality (HR: 1.82; 95% CI: 1.13 to 2.93; p = 0.014). Randomization to spironolactone was associated with modest but statistically significant reduction in depressive symptoms over the course of the trial (p = 0.014). Conclusions Higher baseline depressive symptoms and worsening depressive symptoms were associated with all-cause mortality. Randomization to spironolactone was associated with modest reduction in depressive symptoms. (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function [TOPCAT]; NCT00094302)
Simulation of laser impact welding for dissimilar additively manufactured foils considering influence of inhomogeneous microstructure

Abstract Introduced is a comprehensive numerical modeling framework that includes microstructure when simulating the laser impact welding (LIW) of metals to study the transient phenomena that occur during weld formation. Such transient phenomena include evolution of shear stresses, plastic strains, thermal response, and material jetting. Inhomogeneous microstructures for two dissimilar foils (aluminum 1100 and stainless steel 304) are first predicted using the Dynamic Kinetic Monte Carlo (KMC) method to simulate laser-based powder bed fusion (PBF-LB) additive manufacturing (AM). These microstructures are subsequently incorporated into an Eulerian finite element (FE) simulation of the LIW process, enabling prediction of grain elongations that result from the varying yield surfaces, stacking fault energies, and grain-boundary sliding effects. Trends in the predicted microstructure deformation patterns show strong agreement with those from experimental images in the literature. Compared to existing homogeneous models, the new framework with inhomogeneous AM microstructure reveals higher collision velocities at the weld interface, resulting in increased plastic strain rates, greater plastic heat dissipation, and increased material jetting with higher jet temperatures. The framework allows for new opportunities to study correlations between grain topography (as well as polycrystalline metal texture) and the transient process phenomena occurring at the impact weld interface.
Lessons for deprescribing from a nonessential medication hold policy in US nursing homes.

Background At the height of the COVID-19 pandemic, a large nursing home chain implemented a policy to temporarily hold potentially unnecessary medications. We describe rates of held and discontinued medications after a temporary hold policy of potentially unnecessary or nonessential medications. Methods This retrospective cohort study uses electronic health record (EHR) data on 3247 residents of 64 nursing homes operated by a multistate long-term care provider. Medications were documented in the electronic medication administration record. Overall medication held and discontinued incidences are reported. Hierarchical Bayesian modeling is used to determine individual probabilities for medication discontinuation within each facility. Results In total, 3247 residents had 5297 nonessential medications held. Multivitamins were most likely to be held, followed by histamine-2 receptor antagonists, antihistamines, and statins. At the end of the hold policy, 2897 of 5297 (54%) were permanently discontinued, including probiotics (73%), histamine-2 receptor antagonists (66%), antihistamines (64%), and statins (45%). Demographics, cognitive and functional impairment were similar between residents with medications who were discontinued versus continued. For most medications, more than 50% of the variance in whether medications were discontinued was explained by facility rather than resident-level factors. Conclusion A temporary medication hold policy implemented during the CoVID-19 pandemic led to the deprescribing of a plurality of 'nonessential' medications. This type of organization-wide initiative may be an effective mechanism for altering future prescribing behaviors to reduce the use of unnecessary medications.
Chapter Four - Choice from among Intentionally Selected Options

Abstract How do people choose among a set of options? Previous work has provided either normative accounts of choice (suggesting that options maintain fixed utility) or subjective accounts (suggesting that utilities are context dependent). Neither account fully explains the systematicity and variability of people's choice behavior. We propose a novel factor, the intentional selection assumption. When people are provided with a set of options to choose among, they treat the set of options as an intentional selection by a person with a specific question in mind. By considering the likely relevant features of the options, the model shows how consideration of the goals and beliefs of the individual presenting the options can help resolve uncertainty about, and lead to variability in, the relative utilities of the options. We discuss how our model explains previous behavioral data and helps to bridge the normative and subjective accounts in the literature.
Inherited Defects and Gene Therapy

Genetic defects vary from trivial to life threatening. Although we tend to think of inherited conditions such as cystic fibrosis and muscular dystrophy as diseases, we often refer to cleft palates or color blindness as inherited defects. However, they are all due to mutations in DNA, the genetic material. Not only are some diseases directly caused by mutations, but susceptibility to infectious disease and to factors such as radiation also is influenced by a variety of genes. True human genetic engineering is still in the future. At present, genetic engineering is restricted to nonhumans and has resulted in the creation of transgenic plants and animals. Eugenics refers to deliberate improvement of the human race by selective breeding. Early eugenic proposals were based on choosing superior parents by visual inspection or medical screening and breeding them in much the same way as for prize pigs and pedigreed dogs. Today, we have reached the position where direct alterations of the human genome at the DNA level are technically feasible although still clumsy.
The effects of word prediction and text-to-speech technologies on the narrative writing skills of students with specific learning disabilities

This study investigated the effects of word prediction and text-to-speech on the narrative composition writing skills of 6, fifth-grade Hispanic boys with specific learning disabilities (SLD). A multiple baseline design across subjects was used to explore the efficacy of word prediction and text-to-speech alone and in combination on four dependent variables: writing fluency (words per minute), syntax (T-units), spelling accuracy, and overall organization (holistic scoring rubric). Data were collected and analyzed during baseline, assistive technology interventions, and at 2-, 4-, and 6-week maintenance probes. Participants were equally divided into Cohorts A and B, and two separate but related studies were conducted. Throughout all phases of the study, participants wrote narrative compositions for 15-minute sessions. During baseline, participants used word processing only. During the assistive technology intervention condition, Cohort A participants used word prediction followed by word prediction with text-to-speech. Concurrently, Cohort B participants used text-to-speech followed by text-to-speech with word prediction. The results of this study indicate that word prediction alone or in combination with text-to-speech has a positive effect on the narrative writing compositions of students with SLD. Overall, participants in Cohorts A and B wrote more words, more T-units, and spelled more words correctly. A sign test indicated that these perceived effects were not likely due to chance. Additionally, the quality of writing improved as measured by holistic rubric scores. When participants in Cohort B used text-to-speech alone, with the exception of spelling accuracy, inconsequential results were observed on all dependent variables. This study demonstrated that word prediction alone or in combination assists students with SLD to write longer, improved-quality, narrative compositions. These results suggest that word prediction or word prediction with text-to-speech be considered as a writing support to facilitate the production of a first draft of a narrative composition. However, caution should be given to the use of text-to-speech alone as its effectiveness has not been established. Recommendations for future research include investigating the use of these technologies in other phases of the writing process, with other student populations, and with other writing styles. Further, these technologies should be investigated while integrated into classroom composition instruction.
“Don’t Just Talk About It; Be About It”: Doing Equity Work in Mathematics Education

During the last few decades, equity concerns have become a priority for some researchers and mathematics (education) organizations. Scholars have begun to address issues of equity through a critical lens (e.g., Boaler, 2007; Darling-Hammond, 2005; Martin, 2003) in their work and scholarship. In this article, the author seeks to add to the equity discourse by examining equity research pertinent to mathematics education. He encourages scholars to continue the critical dialogue concerning crafting fruitful equity research agendas, initiatives, etc. that will yield more equitable mathematics educational experiences, especially for students of color. The author concludes the article by challenging readers to move from scholar to activist as it relates to working on the frontlines in their respective spaces to produce equitable mathematics outcomes.
Treegion Scheduling for Highly Parallel Processors

Instruction scheduling is a compile-time technique for extracting parallelism from programs for statically scheduled instruction level parallel processors. Typically, an instruction scheduler partitions a program into regions and then schedules each region. One style of region represents a program as a set of decision trees or treegions. The non-linear nature of the treegion allows scheduling across multiple paths. This paper presents such a technique, termed treegion scheduling. The results of experiments comparing treegion scheduling to scheduling for basic blocks and across “simple linear regions” show that treegion scheduling outperforms the other techniques.
Identification of Physiological Function of Gut Peptides

The sections in this article are: 1 Identification of Hormones 1.1 Criteria 1.2 Selective Ablation 1.3 Mimicry 1.4 Use of Specific Antisera and Selective Antagonists 2 Identification of Paracrine Peptides 2.1 Criteria 2.2 Antral Somatostatin: Paracrine Regulator of Antral Gastrin Secretion 2.3 Fundic Somatostatin: Paracrine Regulator of Acid Secretion 3 Identification of Peptide Neurotransmitters 3.1 Criteria 3.2 Topography of Peptide-Containing Neurons 3.3 Properties of Neuropeptides of the Gut 3.4 Identification of Neurotransmitter Function
Nosocomial influenza infection as a cause of intercurrent fevers in infants.

All patients on an infants9 ward manifesting intercurrent fevers were studied for viral and bacterial etiology during a community outbreak of influenza A. During a one-month period, of 29 infants admitted to the ward, 17 were hospitalized for seven or more days. Intercurrent fever complicated the course of 13 (76%) of these 17 infants. Nosocomially acquired influenza A infection was found in 12 (92%) of the 13 infants. Two of these also contracted a dual infection with influenza B. The fever lasted an average of 2.7 days with a peak of 38.2 to 39.8 C. Initial white blood cell counts tended to be high and Shifted to the left. These infants appeared to be at high risk for developing lower respiratory tract disease. Seven of the 12 had infiltrates on chest X-ray, and five subsequently developed a secondrly bacterial pneumonia. These infants tended to be young, five were under 6 months, and all but one had underlying cardiorespiratory disease. They also appeared to have prolonged shedding of influenza virus from their nasal secretions. Six of seven shed the virus for 7 to 21 days.
The measurement of carbon monoxide and methane in the National Capital Air Quality Control Region. I - Measurement systems

The Carbon Monoxide Pollution Experiment (COPE) and the National Capital Air Quality Control Region (NCAQCR) undertook a series of measurements of atmospheric CO and CH4 to determine the accuracy of the airborne COPE Correlation Interfer4meter. The device, a modified Michelson interferometer, measures the atmospheric column density of CO and CH4 at 2.3 microns with tropospheric measurement sensitivities of 70 and 10 PPB, respectively. Data for evaluating the remote measurements included atmospheric column density measurements at a ground truth site using a van-mounted infrared Fourier spectrometer; continuous ground level gas chromatographic measurements; and chromatographic data from atmospheric grab samples collected by aircraft and at ground locations. The instruments and sampling techniques used in the experiment are described in detail.
Neurodevelopmental Outcomes in Children with Down Syndrome and Infantile Spasms

Down syndrome (DS) is the most common genetic cause of intellectual disability in the United States. The prevalence of seizure in individuals with DS is 1-13%, and infantile spasm (IS) occurs in 6-32% of those with seizures. Since IS is relatively common in children with DS, it is important to understand the impact IS has on the neurodevelopmental outcomes in order to provide appropriate anticipatory guidance to help maximize the potential of these children. Our study is the first to compare the neurodevelopmental outcomes of children with DS and IS (DS + IS) to children with DS and no history of seizures (DS - IS). Using the Bayley Scales of Infant and Toddler Development III, we assessed the neurodevelopment of 29 subjects (eight DS + IS and 21 DS - IS). Neurodevelopmental outcome was poor in the DS + IS cohort, but the delay in treatment does not appear to contribute to any differences in their developmental scores. However, when compared to children with DS - IS, the DS + IS cohort scored approximately 20 points less in all domains including cognitive, motor, and language (P < 0.05). Our results indicate that IS may impact the neurodevelopmental outcomes of children with DS + IS; thus, it is important to provide ongoing developmental and educational assessments and potentially additional therapies for children with DS + IS.
Prolactin regulation of mouse mammary tumor virus (MMTV) expression in normal mouse mammary epithelium

Abstract The hormonal regulation of mouse mammary tumor virus (MMTV) RNA in normal mouse mammary epithelium was studied in an expiant system. In tissue from parous mice, physiological concentrations of prolactin stimulated MMTV expression, while only pharmacological concentrations of cortisol were effective. Regulation in expiants from virgin mice was similar to that in parous animals except that the former were less sensitive to prolactin; this relative unresponsiveness may explain why uninduced tissue from virgin mice does not express MMTV RNA, while that from parous mice does exhibit some basal production. These results suggest that prolactin plays a major role in MMTV expression in normal mammary epithelium and that glucocorticoids may only have a permissive effect or may act through an indirect mechanism requiring high concentrations. These data also suggest that the greater susceptibility of parous mice to MMTV-induced tumorigenesis may reflect the greater prolactin sensitivity in the glands from these animals.