cssi/SciSciGPT-SciSciNet huggingface dataset:
The Impact of the Hepatocyte-to-Plasma pH Gradient on the Prediction of Hepatic Clearance and Drug-Drug Interactions for CYP2D6 Substrates

Surrogate assays for drug metabolism and inhibition are traditionally performed in buffer systems at pH 7.4, despite evidence that hepatocyte intracellular pH is 7.0. This pH gradient can result in a pKa-dependent change in intracellular/extracellular concentrations for ionizable drugs that could affect predictions of clearance and P450 inhibition. The effect of microsomal incubation pH on in vitro enzyme kinetic parameters for CYP2C9 (diclofenac, (S)-warfarin) and CYP3A4 (midazolam, dextromethorphan, testosterone) substrates, enzyme specific reversible inhibitors (amiodarone, desethylamiodarone, clozapine, nicardipine, fluconazole, fluvoxamine, itraconazole) and a mechanism-based inhibitor (amiodarone) was investigated. Intrinsic clearance through CYP2C9 significantly increased (25% and 50% for diclofenac and (S)-warfarin respectively) at intracellular pH 7.0 compared with traditional pH 7.4. The CYP3A4 substrate dextromethorphan intrinsic clearance was decreased by 320% at pH 7.0, while midazolam and testosterone remained unchanged. Reversible inhibition of CYP2C9 was less potent at pH 7.0 compared with 7.4, while CYP3A4 inhibition potency was variably affected. Maximum enzyme inactivation rate of amiodarone toward CYP2C9 and CYP3A4 decreased at pH 7.0, while the irreversible inhibition constant remained unchanged for CYP2C9, but decreased for CYP3A4 at pH 7.0. Predictions of clearance and drug-drug interactions made through physiologically based pharmacokinetic models were improved with the inclusion of predicted intracellular concentrations based at pH 7.0 and in vitro parameters determined at pH 7.0. No general conclusion on the impact of pH could be made and therefore a recommendation to change buffer pH to 7.0 cannot be made at this time. It is recommended that the appropriate hepatocyte intracellular pH 7.0 be used for in vitro determinations when in vivo predictions are made.
The switch from patents to state-dependent prizes for technological innovation

Abstract The intertemporal-bounty system is proposed to replace patents by requesting innovators to place innovations in the public domain in exchange for bounty claims. This eliminates monopoly distortions. As tradeable assets, bounty claims can earn intertemporal bounties or state-dependent prizes, conditioned on time-varying market sales from bountiable goods multiplied by a time-invariant bounty rate. Creative destruction can make some bounty claims worthless, however. Government collects taxes to pay bounties. The switch from patents to intertemporal bounties is simulated using an R&D-based growth model calibrated to the U.S. economy. Funded by a tax on labor income, the regime switch can generate a consumption-equivalent welfare gain of 7%. This is considered the maximum opportunity cost to keep the U.S. patent system, as the labor income tax is non-distortionary in the model. Funded by the distortionary capital income tax, the regime switch can remain welfare-improving, provided the bounty rate is set appropriately.
Gender-fluid Geek Girls: Negotiating Inequality Regimes in the Tech Industry

How do technically-skilled women negotiate the male-dominated environments of technology firms? This article draws upon interviews with female programmers, technical writers, and engineers of diver...
An Alternative Triangle Area Strategy.

We explore the mathematics engagement of a group ofmathematics coaches, working in k-12 mathematics education. The incenter of a triangle is used to derive an alternative formula for the area of a triangle inspired by Usiskin, Peressini, Marhisotto, and Stanley (2002).
Bordering Spaces, Practising Borders: Fences, Roads and Reorientations across a Nepal–China Borderland

ABSTRACTInfrastructure developments across the trans-Himalaya have rapidly advanced Nepali and Chinese state presences across spaces where central governance has long been absent. This study examines how new border infrastructures of fences and roads shape commercial and cultural relationships between Mustang (Nepal) and Tibet and the ways in which these processes serve state-making purposes for both Nepal and China through the governance of highland–borderland landscapes. A Tibetan cultural region at Nepal's northern border, Mustang's human and physical geography supports trade corridors that link the Tibetan Plateau with the plains of India. Merchants, mendicants and militaries have traversed these trade routes for centuries, giving rise to a unique social landscape that largely transcends modern demarcations of a bordered world. Looking across the trans-Himalaya, this article argues that as Chinese and Nepali authorities introduce new material structures and institutional practices to regulate and soli...
Clinical accuracy of preoperative breast MRI for breast cancer

Background It is unclear if breast magnetic resonance imaging (MRI) is more accurate than mammography (MGM) and ultrasound (U/S) in aggregate for patients with invasive cancer. Methods We compared concordance of combined tumor size and tumor foci between MRI and MGM and U/S combined to pathological tumor size and foci as the gold standard from 2009 to 2015. Tumor size was nonconcordant if it differed from the pathologic size by ≥33% and tumor foci was nonconcordant if >1 foci were seen. If one or both of the MGM or U/S was nonconcordant and the MRI was concordant, MRI provided greater accuracy. Results Of 471 patients with MGM, US, and MRI, MRI was more accurate for 32.9% of patients for tumor size and for 21.9% for tumor foci. Patients for whom MRI had greater accuracy were compared to those who did not for clinical and tumor factors. The only significant factor was calcifications on mammography. Tumor size, stage, molecular subtype, histology, grade, patient BMI, age, mammographic density, and use of hormone replacement therapy were not significantly different. Conclusions Breast MRI provides greater accuracy for a third of patients undergoing preoperative MGM and U/S. Mammographic calcifications were associated with MRI clinical accuracy for patients with invasive cancer.
The contribution of double-crested cormorants (Phalacrocorax auritus) to silver carp (Hypophthalmichthys molitrix) DNA loads in the Chicago Area Waterway System

Abstract Waterfowl and colonial waterbirds can have significant impacts on water quality in lakes and reservoirs by depositing feces that contribute to nitrogen and phosphorus loads. Piscivorous birds can also contribute the DNA of prey species to a water body. Here, we develop and apply a loading model to estimate the number of silver carp (Hypophthalmichthys molitrix) DNA target marker copies that are potentially deposited by nesting double-crested cormorants (Phalacrocorax auritus) in the Chicago Area Waterway System (CAWS). The model assumes a conservative breeding population estimate ranging between 6000 and 8000 cormorants distributed among three large colonies in the Chicago metropolitan area. The model also assumes that cormorants are distributing feces randomly throughout the CAWS in proportion to the amount of time spent at each location. Results show that cormorants may be contributing 2.6 to 113 target marker copies/m2/day if birds are spending 22% of their time on open water and 6.4 to 291 target marker copies/m2/day if birds are spending 56% of their time on open water. Over the entire CAWS, cormorants may contribute tens of millions to billions of silver carp DNA copies each day. These target marker loads may be contributing to positive detections of silver carp environmental DNA (eDNA) in the CAWS. This study does not address other potential sources of silver carp genetic material in the CAWS, including live fish, and provides no indication as to whether or not the loads attributed to cormorants are large or small in relation to these other potential sources.
Surgical unroofing of intramural anomalous aortic origin of a coronary artery in pediatric patients: Single-center perspective

Abstract Background Intramural anomalous aortic origin of a coronary artery (AAOCA) is associated with an increased risk of sudden cardiac death. This is amenable to surgical coronary unroofing, but outcomes studies are lacking. Objective To perform a comprehensive review of our institutional experience with pediatric patients with AAOCA who underwent surgical repair with unroofing of the intramural segment, focusing on preoperative and postoperative course and testing as well as intraoperative findings. Methods A retrospective cohort study was conducted to evaluate patients with AAOCA status post–coronary unroofing at Children's Hospital of Wisconsin. Data extraction included symptoms, preoperative and postoperative imaging and testing, surgical findings, and postoperative clinical course. Results From January 1999 to December 12, 2015, 63 patients underwent unroofing at a median age of 13 years (0.5-18 years). The majority underwent unroofing of an intramural right coronary (79%); 21% had an intramural left AAOCA. Symptoms suggestive of possible ischemia were present in about 50%. Additional structural cardiac anomalies were present in 33%. Transthoracic echocardiography was diagnostic in 60 of 63 (95%) and correlated with surgical findings in all cases. There was no surgical mortality associated with the unroofing, and no additional coronary reinterventions were performed. The median duration of postoperative follow-up was 3.1 years (7 days to 13.6 years). Symptoms either persisted or developed in 46% postoperatively. Postoperative exercise stress testing, stress echocardiography, and cardiac magnetic resonance imaging were performed in 76%, 8%, and 20%, respectively, of the cohort. None identified findings consistent with reversible coronary ischemia. Three patients had sudden cardiac arrest (1 death) after surgery without an identified residual coronary abnormality. Conclusions Transthoracic echocardiography, with carefully designed coronary imaging protocols, can be diagnostic in accurately identifying intramural AAOCA in pediatric patients. Unroofing can be performed safely with no early morbidity, but symptoms can persist (including rare life-threatening events) without evidence of ischemia by postoperative provocative testing.
Developing Social Work Skills for Work with Volunteers

To help overcome their resistance, workers need to understand the difference between professional and volunteer roles, the nature of a volunteer development system, the self-actualization aspect of...
Effect of Benomyl Application and Spawnmate Supplementation on Yield and Size of Selected Genotypes of Pleurotus SPP.

Abstract Royse, D. J., and Schisler, L. C., 1986. Effect of benomyl application and SpawnMate supplementation on yield and size of selected genotypes of Pleurotus spp . Benomyl, applied in the substrate soak water, significantly increased the yield response of Pleurotus spp . to increasing levels of SpawnMate supplementation. Yields were 80% higher with benomyl-soaked substrate supplemented with SpawnMate at 63% (dry substrate weight) compared to similar substrate nontreated with benomyl. Benomyl effectively controlled growth of competitor weed molds in the substrate. Yields were 9 fold higher on benomyl-soaked substrate supplemented with 63% SpawnMate compared to benomyl-soaked substrate nonsupplemented. As biological efficiencies increased, moisture contents, at crop termination, decreased (r= -0. 911). A differential size response to SpawnMate supplementation was observed for Pleurotus spp . genotypes. Size for line 537 generally decreased with increasing levels of supplementaion. The opposite response was observed for line 444. Mushrooms of line 444 were harvested as many as 12 to 14 days earlier from Spawn Mate supplemented substrate compared to nonsupplemented substrate.
Individual Nano-Objects Obtained via Hierarchical Assembly of Polymer Building Blocks

This chapter emphasizes synthetic methodological approaches toward complex nano-objects for which the term ‘complex’ is defined as ‘originating from several parts’. Those parts are polymer building blocks that are assembled hierarchically to achieve final nanoscopic structures that could not be constructed from small molecules in a single step. The state of the art has evolved from primitive methods that demonstrate control over the size of individual nanoscopic objects to elaborate schemes that exert fine-tuning of the composition, structure, and properties of multifunctional nanoscopic devices. The assembly, stabilization, and manipulation of polymers in solution, in the bulk, and in the presence of templates are discussed, with various examples being presented to demonstrate the roles of the polymer structure and the conditions applied to afford diverse types of nanostructured materials.
Advertisement, Discovery and Agreement

The modeling methodology in Chap. 16 assumes that an enterprise defines its business processes and already knows all trading partners that it wants to integrate with those using B2B integration technology. This means that the enterprise either already conducts business with the trading partners or they agreed to do business with each other in the future, as soon as the business processes are specified.
Coverage and Rate Maximization via User Association in Multi-Antenna HetNets

We formulate two statistical optimization frameworks for multi-antenna heterogeneous networks (HetNets). The first one maximizes coverage, via user association, and the second one maximizes a rate utility function by jointly optimizing user association and the spectrum allocated to each tier. Since both performance metrics depend on the coverage probability, we first derive the exact analytical coverage expression for a frequency-partitioned multi-antenna HetNet. We then present a simple closed-form approximation using the Gil-Pelaez inversion theorem, making both optimization frameworks concave in the optimizing variables. We show that to maximize coverage, the user should connect to the tier with the highest ratio of the array gain to the multiplexing gain, highlighting that max-power association becomes far from optimal in terms of coverage. To maximize the rate utility, we show that the optimal resource allocation of a tier is equal to the portion of users connected to that tier. Furthermore, maximizing the rate utility breaks down into maximizing two objectives: coverage and the number of users to be served in a resource block. Several theoretical insights are presented and further validated via simulations, showing that both frameworks provide considerable coverage and rate gains compared to the standard max-power and small-cell range expansion schemes.
Human eIF5 and eIF1A Compete for Binding to eIF5B

Eukaryotic translation initiation is a multistep process requiring a number of eukaryotic translation initiation factors (eIFs). Two GTPases play key roles in the process. eIF2 brings the initiator Met-tRNAi to the preinitiation complex (PIC). Upon start codon selection and GTP hydrolysis promoted by the GTPase-activating protein (GAP) eIF5, eIF2-GDP is displaced from Met-tRNAi by eIF5B-GTP and is released in complex with eIF5. eIF5B promotes ribosomal subunit joining, with the help of eIF1A. Upon subunit joining, eIF5B hydrolyzes GTP and is released together with eIF1A. We found that human eIF5 interacts with eIF5B and may help recruit eIF5B to the PIC. An eIF5B-binding motif was identified at the C-terminus of eIF5, similar to that found in eIF1A. Indeed, eIF5 competes with eIF1A for binding and has an ∼100-fold higher affinity for eIF5B. Because eIF5 is the GAP of eIF2, the newly discovered interaction offers a possible mechanism for coordination between the two steps in translation initiation controlled by GTPases: start codon selection and ribosomal subunit joining. Our results indicate that in humans, eIF5B displacing eIF2 from Met-tRNAi upon subunit joining may be coupled to eIF1A displacing eIF5 from eIF5B, allowing the eIF5:eIF2-GDP complex to leave the ribosome.
Measuring novel antecedents of mental illness: the Questionnaire of Unpredictability in Childhood.

Increasing evidence indicates that, in addition to poverty, maternal depression, and other well-established factors, unpredictability of maternal and environmental signals early in life influences trajectories of brain development, determining risk for subsequent mental illness. However, whereas most risk factors for later vulnerability to mental illness are readily measured using existing, clinically available tools, there are no similar measures for assessing early-life unpredictability. Here we validate the Questionnaire of Unpredictability in Childhood (QUIC) and examine its associations with mental health in the context of other indicators of childhood adversity (e.g., traumatic life events, socioeconomic status, and parenting quality). The QUIC was initially validated through administration to a cohort of adult females (N = 116) and then further refined in two additional independent cohorts (male Veterans, N = 95, and male and female adolescents, N = 175). The QUIC demonstrated excellent internal (α = 0.89) and test-retest reliability (r = 92). Scores on the QUIC were positively correlated with other prospective indicators of exposures to unpredictable maternal inputs in infancy and childhood (unpredictable maternal mood and sensory signals), and accuracy of recall also was confirmed with prospective data. Importantly, the QUIC predicted symptoms of anxiety, depression, and anhedonia in the three study cohorts, and these effects persisted after adjusting for other previously established risk factors. The QUIC, a reliable and valid self-report assessment of exposure to unpredictability in the social, emotional, and physical domains during early life, is a brief, comprehensive, and promising instrument for predicting risk for mental illness.
Maintaining product quality in raisins throughout the introgression of powdery mildew resistance

The availability of powdery mildew-resistant raisin accessions will lower grower production costs and enhance the environment through reduced fungicide use. To achieve this objective, backcrossing ...
Mapping the agricultural drought based on the long-term AVHRR NDVI and North American Regional Reanalysis (NARR) in the United States, 1981–2013

Abstract To provide a long-term perspective of drought variability from 1981 to present, we develop a new monthly agriculturally-based drought index called the Integrated Scaled Drought Index (ISDI). This index integrates Normalized Difference Vegetation Index (NDVI) from Advanced Very High Resolution Radiometer (AVHRR) data (available from 1981 to present), land surface temperature (LST), precipitation (PCP), and soil moisture (SM) data from North American Regional Reanalysis (NARR) project (available from 1979 to present). This new agriculturally-based drought index incorporates important components controlling agricultural drought, particularly soil moisture, for which there are limited in-situ observations through time and across space. The optimum weights for each component of the ISDI are determined by correlation analysis with commonly used in-situ drought indices, such as the Palmer Drought Severity Index (PDSI), the Palmer Modified Drought Index (PMDI), the Palmer's Z-index, and the Standardized Precipitation Index (SPI) at different time scales. Resulting ISDI maps are also visually compared with United States Drought Monitor (USDM) and Vegetation Drought Response Index (VegDRI) maps for empirical validation. ISDI shows strong agreement with these two national-wide drought monitoring systems. ISDI also shows strong linear correlations with corn yield anomalies in July and with soybean yield anomalies in August and strong spatial correspondence with county-level corn/soybean yield anomalies during major drought events. These results illustrate the robustness and usefulness of ISDI. This agriculturally-based drought index integrates the benefits of numerical model simulation and remote sensing technology to account for interannual variability of drought for the longest possible time-frame in the satellite era. This long-term monthly drought index provides a longer historical perspective of drought impacts since 1981. It can be generalized to incorporate other satellite data or in-situ observation and has the potential for operational drought monitoring and assessment.
Output-Only Modal Parameter Estimation Using a Continuously Scanning Laser Doppler Vibrometer System with Application to Structural Damage Detection

Spatially dense vibration measurement can be obtained by use of a continuously scanning laser Doppler vibrometer (CSLDV) system that sweeps its laser spot along a scan path. For a linear, time-invariant, viscously damped structure undergoing free vibration, a new type of vibration shapes called free response shapes was defined and obtained by the authors using a CSLDV system with the demodulation method. To date, application of free response shapes is limited to structural damage identification, and they cannot be directly used for model validation while mode shapes can be. This paper extends the concept of free response shapes by proposing a new output-only modal parameter estimation (OMPE) method using a CSLDV system to estimate modal parameters of the structure undergoing free vibration, including natural frequencies, modal damping ratios, and mode shapes. Advantages of the proposed method are: (1) modal damping ratios and mode shapes can be accurately estimated from obtained free response shapes, (2) the scanning frequency of the CSLDV system can be relatively low, and (3) estimated mode shapes can be used for structural damage identification as if they were measured by stepped scanning of a scanning laser Doppler vibrometer. A baseline-free method is applied to identify structural damage using mode shapes estimated by the proposed OMPE method. The analytical expression of free response shapes of the structure is derived, based on which the OMPE method is proposed and presented as a step-by-step procedure. In the proposed OMPE method, natural frequencies of the structure are identified from free response of certain fixed points on the structure; its modal damping ratios and mode shapes are simultaneously estimated using free response shapes measured by a CSLDV system. A numerical investigation is conducted to study the OMPE method and its application to baseline-free damage identification with mode shapes estimated by the OMPE method.
Expenditures and Health Care Utilization Among Adults With Newly Diagnosed Low Back and Lower Extremity Pain.

Importance Low back pain (LBP) with or without lower extremity pain (LEP) is one of the most common reasons for seeking medical care. Previous studies investigating costs in this population targeted patients receiving surgery. Little is known about health care utilization among patients who do not undergo surgery. Objectives To assess use of health care resources for LBP and LEP management and analyze associated costs. Design, Setting, and Participants This cohort study used a retrospective analysis of a commercial database containing inpatient and outpatient data for more than 75 million individuals. Participants were US adults who were newly diagnosed with LBP or LEP between 2008 and 2015, did not have a red-flag diagnosis, and were opiate naive prior to diagnosis. Dates of analysis were October 6, 2018, to March 7, 2019. Exposures Newly diagnosed LBP or LEP. Main Outcomes and Measures The primary outcome was total cost of care within the first 6 and 12 months following diagnosis, stratified by whether patients received spinal surgery. An assessment was performed to determine whether patients who did not undergo surgery received care in accordance with proposed guidelines for conservative LBP and LEP management. Costs resulting from use of different health care services were estimated. Results A total of 2 498 013 adult patients with a new LBP or LEP diagnosis (median [interquartile range] age, 47 [36-58] years; 1 373 076 [55.0%] female) were identified. More than half (55.7%) received no intervention. Only 1.2% of patients received surgery, but they accounted for 29.3% of total 12-month costs ($784 million). Total costs of care among the 98.8% of patients who did not receive surgery were $1.8 billion. Patients who did not undergo surgery frequently received care that was inconsistent with clinical guidelines for LBP and LEP: 32.3% of these patients received imaging within 30 days of diagnosis and 35.3% received imaging without a trial of physical therapy. Conclusions and Relevance The findings suggest that surgery is rare among patients with newly diagnosed LBP and LEP but remains a significant driver of spending. Early imaging in patients who do not undergo surgery was also a major driver of increased health care expenditures. Avoidable costs among patients with typically self-limited conditions result in considerable economic burden to the US health care system.
Data related to the synthesis, characterization and electrochemical performance of high capacity sodium manganese periodate electrodes.

Abstract Sodium manganese periodate compounds were synthesized to serve as high capacity cathodes. The composition and morphology of resulting products were characterized by scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), X-ray Diffraction (XRD) and thermogravimetric analysis (TGA). Composite cathodes made from the synthesized periodates were used to fabricate batteries with zinc anode and acetic acid electrolyte. Electrode formulations were optimized using nanocarbon conductive additives. For the full design and mechanism related to the sodium manganese periodate electrode with specific capacity as high as 750 mAh g -1 , please refer to our research article “High Capacity Aqueous Periodate Batteries Featuring a Nine-Electron Transfer Process” [1] .
The risk-shifting value of payout: Evidence from bank enforcement actions

Abstract This paper reexamines whether investors value payout and why. I study abnormal stock returns around regulatory enforcement actions that restrict bank dividends and repurchases. Market reactions are significantly worse for enforced banks that pay out than for those that do not. Withstanding alternative explanations and parallel trend concerns, these results present rare, causal evidence of a value to corporate distribution. The cross-section of abnormal returns suggests that risk-shifting, not agency cost-reduction, drives payout. In my sample of distressed banks, especially around financial crises, the ability to shift risk through payout has value.
On the rapid expansion of optimality theory at the end of the twentieth century

Summary Despite being a recent development in generative linguistics, Optimality Theory (OT, Prince & Smolensky 1993) has had a profound impact on linguistics, particularly on phonology in North America. OT posits that observed forms of language arise due to conflicting linguistic constraints. When proposed in 1993, OT saw virtually overnight success in American phonology despite not having been the first theory of grammar to focus solely on the constraint. I argue, that the reasons for which OT saw such immediate success due in large part to the efforts of Prince and Smolensky to work at getting the word out, the state of American phonology at the time which felt stagnant to some, and the coincidence of OT’s birth with the Internet Boom which Prince and Smolensky used to their advantage
Hospital-level factors associated with nonoperative management in common pediatric surgical procedures.

Abstract Purpose Our purpose was to examine patient- and hospital-level factors associated with nonoperative management in common pediatric surgical diagnoses. Methods Using the 2012 Kid's Inpatient Database (KID), we identified patients Results Of 36,026 admissions for the diagnoses of interest, 7472 (20.7%) were managed nonoperatively. SPTX had the highest incidence of NONOP (55.9%; n = 394), while PA had the lowest incidence (9.2%; n = 1641). Utilization of operative management varied significantly between hospitals. Patients diagnosed with BO (OR 0.41; 95% CI 0.30–0.56) and SPTX (OR 0.28; 95% CI 0.14–0.56) had decreased odds of operative management when treated at an urban, teaching hospital compared to a rural hospital. Patients with PA had increased odds of operative management when treated at an urban, teaching hospital (OR 2.42; 95% CI 1.78–3.30). Hospital-level factors associated with decreased odds of nonoperative management included urban, nonteaching status (OR 0.54; 95% CI 0.31–0.91) and location in the South (OR 0.53; 95% CI 0.34–83) and West (OR 0.47; 95% CI 0.30–0.74). Conclusions Despite representing more than 20% of pediatric surgical care for several conditions, nonoperative management is an understudied aspect of care with significant variation that warrants further research. Level of evidence III
Reflections on Practice: Providing Authentic Experiences with Families in Early Childhood Teacher Education.

Teachers’ positive relationships with families contribute to the social, emotional, and intellectual development of children in early childhood education programs. Effectively involving, communicat...
Increasing awareness, sensitivity, and empathy for Alzheimer's dementia patients using simulation.

Abstract Background Alzheimer's Disease (AD), a type of dementia that interferes with memory, thinking, and behavior is the most common type of dementia. As a result, it is a leading contributor to death and disability for those over the age of 65. Therefore, future nurses must have the knowledge and skills to manage patients with AD in any setting spanning the healthcare continuum. Objective The goal of this project was to evaluate perceptions of awareness, knowledge and sensitivity of future nurses concerning AD patients before and after participation in a simulated virtual reality dementia experience. Design/Participants. A quasi-experimental repeated measure pre-post design was used with a convenience sample of 163 undergraduate baccalaureate nursing students from three different courses at large public university in the Midwest. Methods Students were placed in teams of four to participate in a 45-minute interactive simulated virtual reality dementia experience. Each session started with a 15-minute team pre-briefing session, followed by a 10-minute individual simulation, which was then followed by a 30-minute team debriefing session facilitated by faculty using the Plus/ Delta debriefing technique. The Dementia Attitudes Scale (DAS), The Knowledge About Memory Loss and Care Test (KAML-C), and the Healthcare Tour Survey were administered pre/post participation. Qualitative data was also collected from student reflections. Results Statistically significant changes (p Conclusion Using a virtual reality dementia experience proved to be a valuable strategy to increase student perceptions of awareness, knowledge, and sensitivity of AD. Further exploration is warranted to establish how these may be further facilitated to translate into improved care for those with AD.
30‐day patient reported outcomes can be predicted by change in left atrial pressure and not change in transmitral gradient following MitraClip

BACKGROUND Change in left atrial pressure (LAP) has been shown to be associated with symptom improvement post-MitraClip; however, the association between acute procedural changes in transmitral diastolic mean gradient (MG) compared to LAP and symptom improvement is not well established. METHODS 164 consecutive patients undergoing MitraClip at Mayo Clinic between June 2014 and May 2018 were included. Preclip and postclip MG and LAP were recorded. Baseline demographics, clinical, and echocardiographic outcomes, including 30-day New York Heart Association (NYHA) functional status were obtained from patient charts. RESULTS Median age was 81.5 years (IQR: 76.3, 87), 34% were female and 94.5% had NYHA class III and IV functional status at baseline. At baseline, median MG was 4 mmHg (IQR: 3, 5) and LAP was 19 mmHg (IQR: 16, 23.5). Following MitraClip deployment, the median MG was 4 mmHg (IQR: 3, 6) and the median LAP was 17 mmHg (IQR: 14, 21), 69.5% of patients had less than moderate MR. There was no statistically significant association between change in MG and NYHA functional class at 30 days (OR = 0.95, 95% CI: 0.76-1.20). However, a reduction in LAP following MitraClip deployment was significantly associated with improvement in NYHA functional status at 30 days following adjustments for age and sex (aOR 3.36, 95% CI: 1.34-8.65). There was no significant correlation between change in mean LAP and change in MG (p = .98). CONCLUSION Unlike change in left atrial pressure, change in MG post-MitraClip was not associated with patient reported outcomes at 30 days and did not correlate with change in left atrial pressure. Long-term follow up is needed to evaluate the impact of LA pressure on symptoms.
Promoting Diversity, Equity, and Inclusion in Library and Information Science through Community-Based Learning

This paper contends that Community-Based Learning (CBL) promotes diversity, equity, and inclusion (DEI) in Library and Information Science and iSchool education. First, we set forth our methodological approach, which is a qualitative case study. Next, we review the literature on diversity, experiential learning, and Community-Based Learning (CBL). Third, we describe how one iSchool is implementing community-based learning in a novel way by embracing data science and design thinking in its pedagogical approach to a new three-course, twelve-credit post-Baccalaureate certificate. We discuss the institutional context for the certificate, the project partners, the twelve CBL Fellows, and the curriculum, which includes two new courses (Design Thinking for Digital Community Service and Data Analytics for Community-Based Data and Service) and a capstone. We conclude by offering directions for future research.
Dysregulated Microglial Cell Activation and Proliferation Following Repeated Antigen Stimulation.

Upon reactivation of quiescent neurotropic viruses, (Ag)-specific brain resident-memory CD8+ T-cells (bTRM) may respond to de novo-produced viral Ag through rapid release of IFN-γ, which drives subsequent interferon-stimulated gene expression in surrounding microglia. Through this mechanism, a small number of adaptive bTRM may amplify responses to viral reactivation leading to an organ-wide innate protective state. Over time, this brain-wide innate immune activation likely has cumulative neurotoxic and neurocognitive consequences. We have previously shown that HIV-1 p24 antigen (Ag)-specific bTRM persist within the murine brain using a heterologous prime-CNS boost strategy. In response to Ag re-challenge, these bTRM display rapid and robust recall responses, which subsequently activate glial cells. In this study, we hypothesized that repeated recall responses to viral Ag (modeling repeated episodes of viral reactivation) culminate in prolonged reactive gliosis and exacerbated neurotoxicity. To address this question, mice were first immunized with adenovirus vectors expressing the HIV p24 capsid protein, followed by a CNS-boost using Pr55Gag/Env virus like particles (HIV-VLPs). Following establishment of the bTRM population (>30 d), prime-CNS boost animals were then subjected to in vivo recall stimulation, as well as restimulation (at 14 d post-recall stimulation), using the immunodominant HIV-1 AI9 CD8+ T-cell epitope peptide. In these studies, Ag restimulation resulted in prolonged expression of microglial activation markers and an increased proliferative response, longer than recall stimulation alone. This continued expression of MHCII and PD-L1 (activation markers), as well as Ki67 (proliferative marker) was observed at 7, 14, and 30 d post-AI9 restimulation. Additionally, in vivo restimulation resulted in continued production of inducible nitric oxide synthase (iNOS) with elevated levels observed at 7, 14, and 30 d post-restimulation. Interestingly, iNOS expression was significantly lower among recall-stimulated animals when compared to restimulated groups. Furthermore, in vivo specific Ag restimulation produced lower levels of arginase (Arg)-1 when compared with the recall-stimulated group. Taken together, these results indicate that repeated Ag-specific stimulation of adaptive immune responses leads to cumulative dysregulated microglial cell activation.
Hypophysitis

Hypophysitis is an uncommon inflammatory condition that may affect the pituitary gland and stalk. Patients often present with varying degrees of hypopituitarism. The diagnosis is often made presumptively based on clinical history and biochemical data but may also be supported by magnetic resonance imaging. Therapy is generally supportive in nature but may require surgery for pathological diagnosis and treatment of mass effect.
Constructing information technology (IT) portfolios to achieve enterprise strategic goals in multi-business unit firms

Abstract This study aims to develop a new methodology in IT Portfolio Management (ITPM) to address the impact of portfolio priorities on IT strategies in a multi-business unit firm. The methodology includes a new ITPM model and uses simulated scenarios to overcome limitations due to insufficient real-world organizational IT portfolio data. The weight scores generated by the proposed ITPM model can enable the firm to create a rational viewpoint to improve its IT investment efficiency while establishing IT priorities to achieve enterprise strategic goals. Such an approach would enable firms to reduce their reliance on CIO intuition in guiding firms’ technology portfolios.
Warped Dynamic Linear Models for Time Series of Counts

Dynamic Linear Models (DLMs) are commonly employed for time series analysis due to their versatile structure, simple recursive updating, and probabilistic forecasting. However, the options for count time series are limited: Gaussian DLMs require continuous data, while Poisson-based alternatives often lack sufficient modeling flexibility. We introduce a novel methodology for count time series by warping a Gaussian DLM. The warping function has two components: a transformation operator that provides distributional flexibility and a rounding operator that ensures the correct support for the discrete data-generating process. Importantly, we develop conjugate inference for the warped DLM, which enables analytic and recursive updates for the state space filtering and smoothing distributions. We leverage these results to produce customized and efficient computing strategies for inference and forecasting, including Monte Carlo simulation for offline analysis and an optimal particle filter for online inference. This framework unifies and extends a variety of discrete time series models and is valid for natural counts, rounded values, and multivariate observations. Simulation studies illustrate the excellent forecasting capabilities of the warped DLM. The proposed approach is applied to a multivariate time series of daily overdose counts and demonstrates both modeling and computational successes.
Toward an optimal spectrum for photosynthesis and plant morphology in LED-based crop cultivation

Abstract Photons are simultaneously an energy source for plant growth and a signal for development. Through photosynthesis, plants convert photon energy into chemical energy powering life on the Earth. To maximize survival, plants need to find ways to efficiently capture photons. As sessile organisms, plants must acclimate to seasonal, daily, and hourly fluctuations in their growing environment, and use their local light environment as a signal to initiate developmental changes. Here we review spectral effects on both photosynthesis and plant development—especially on morphology and secondary metabolite synthesis. We discuss the application of these adaptive responses to optimize crop growth and quality in indoor agriculture.
The Spiritual Illusion: Redux

In this response to Knut Melvaer’s discussion of “The Spiritual Illusion: Constructive Steps Toward Rectification and Redescription,” I clarify some of the theoretical and methodological background that informed the original article, redress places where Melvaer appears to have misread or miscast my positions, and offer some suggestions as to what may really be most at stake in this “spiritual” dispute.
Exploring Benefits of a Web based Testing and Training Tool

Abstract Web-based training and testing tools are an important component of learning in numerous higher education institutions. Such tools are often implemented to provide students with more engaging and interactive learning experiences. To assess their benefits for various student success initiatives, an instrument must be developed and validated trough an experiential study/survey. The purpose of this study is to redesign a previously validated instrument and use it to examine the impact of web-based training and testing tools on student learning from students’ perspective and explore students’ satisfaction level with the tool.
A New Distance Measure for Non-rigid Image Matching

We construct probabilistic generative models for the non-rigid matching of point-sets. Our formulation is explicitly Platonist. Beginning with a Platonist super point-set, we derive real-world point-sets through the application of four operations: i) spline-based warping, ii) addition of noise, iii) point removal and iii) amnesia regarding the pointto-point correspondences between the real-world point-sets and the Platonist source. Given this generative model, we are able to derive new non-quadratic distance measures w.r.t. the "forgotten" correspondences by a) eliminating the spline parameters from the generative model and by b) integrating out the Platonist super point-set. The result is a new non-quadratic distance measure which has the interpretation of weighted graph matching. The graphs are related in a straightfoward manner to the spline kernel used for non-rigid warping. Experimentally, we show that the new distance measure outperforms the conventional quadratic assignment distance measure when both distances use the same weighted graphs derived from the spline kernel.
More than a mission statement: Implementing diversity and social justice initiatives within a school of social work

Purpose – Through an organizational case study approach, this paper seeks to describe the ongoing diversity initiative of a graduate school of social work (SSW). Organizational change is usually built around the activities of change agents or teams, who seek to bring about changes in human resources, systems, programs, and services.Design/methodology/approach – Dreachlin's five‐stage model of organizational change (1999), including discovery, assessment, exploration, transformation, and revitalization, was used to analyze the strategic efforts to promote diversity within the SSW.Findings – The final phase of Dreachlin's model, revitalization, has continued to renew and expand the diversity initiative. It is the responsibility of faculty and administrators to continue to develop, implement, monitor, and review the SSW's diversity efforts with regard to the practicum, curriculum, admissions, and climate issues.Originality/value – Lessons learned during the past three years are discussed along with suggestio...
Chemical and physical properties of freezing point-depressing glycoproteins from Antarctic fishes

Glycoproteins were isolated from the blood sera of the Antarctic fishes Trematomus borchgrevinki and Dissostichus mawsoni. Some of these glycoproteins have the unique property of depressing the freezing point of water more than expected on the basis of the number of particles present in solution and are termed active glycoproteins. These freezing point-depressing glycoproteins depress the freezing point of water to the same extent as NaCl on a weight basis. They are composed primarily of threonine (16%), alanine (23%), N-acetylgalactosamine (29%), and galactose (28%). Compared with the active glycoproteins, the inactive ones (which form ideal solutions) have approximately the same composition except that proline is present. The active glycoproteins have been separated into three distinct groups, based on results from ion exchange chromatography and acrylamide gel electrophoresis. The three active glycoproteins occur in equal amounts in the blood sera, have identical compositions on a weight basis, but differ in molecular weights (10,500,17,000 and 21,500 g). Studies of viscosity and circular dichroism and dialysis experiments indicate that the active glycoproteins are expanded molecules, a property which undoubtedly is of importance to their function.
An evaluation of the draft human genome sequence

The completed draft version of the human genome, comprised of multiple short contigs encompassing 85% or more of euchromatin, was announced in June of 2000 (ref. 1). The detailed findings of the sequencing consortium were reported several months later. The draft sequence has provided insight into global characteristics, such as the total number of genes and a more accurate definition of gene families. Also of importance are genome positional details such as local genome architecture, regional gene density and the location of transcribed units that are critical for disease gene identification. We carried out a series of mapping and computational experiments using a nonredundant collection of 925 expressed sequence tags (ESTs) and sections of the public draft genome sequence that were available at different timepoints between April 2000 and April 2001. We found discrepancies in both the reported coverage of the human genome and the accuracy of mapping of genomic clones, suggesting some limitations of the draft genome sequence in providing accurate positional information and detailed characterization of chromosomal subregions.
An unusual presentation of metastatic disease: Cutaneous metastases from pulmonary adenocarcinoma manifesting as widespread plaques

Lung cancer is the leading cause of cancer mortality in the United States.1 Adenocarcinoma is the most common histologic subtype of lung cancer and most frequently metastasizes to the brain, bone, liver, and adrenal glands, respectively.2 Five-year survival for stage IV nonsmall-cell lung cancer is 1%.3 Rarely, lung cancer may exhibit cutaneous metastases.
The Metabolic and Cardiovascular Effects of Hyperthyroidism Are Largely Independent of β-Adrenergic Stimulation

Hyperthyroidism and states of adrenergic hyperactivity have many common clinical features, suggesting similar pathogenic mechanisms of action. The widespread use of beta-adrenergic receptor (betaAR) antagonists (beta-blockers) to treat hyperthyroidism has led to the belief that the physiological consequences of thyroid hormone (TH) excess are mediated in part via catecholamine signaling through betaARs. To test this hypothesis, we compared the response to TH excess in mice lacking the three known betaARs (beta-less) vs. wild-type (WT) mice. Although beta-less mice had a lower heart rate at baseline in comparison to WT mice, the metabolic and cardiovascular responses to hyperthyroidism were equivalent in both WT and beta-less mice. These data indicate that the metabolic and cardiovascular effects of TH excess are largely independent of betaARs. These findings suggest that the efficacy of clinical treatment of hyperthyroidism with beta-blockers is due to antagonism of sympathetic signaling, and that this process functions independently of TH action.