cssi/SciSciGPT-SciSciNet huggingface dataset:
Risk Stratification in Multinodular Goiter: A Retrospective Review of Sonographic Features, Histopathological Results, and Cancer Risk:

Abstract Purpose In the management of thyroid nodules, although the potential for malignancy exists, there is also the potential for overtreatment of subclinical disease. Although the TI-RADS (Thyroid Imaging-Reporting and Data System) system outlines a risk stratification score based on suspicious ultrasound findings, it has not been universally accepted. Many TI-RADS 2 or 3 patients proceed to fine needle aspiration biopsy (FNAB), potentially unnecessarily. The aim of the study was to identify whether lesions within a multinodular goiter (MNG) without suspicious features can be followed with ultrasound rather than biopsied as is recommended for single nodules. Methods Pathology records were retrospectively analysed for proven MNGs over a 5-year period. A total of 293 cases were identified. FNAB, prebiopsy ultrasound images, and reports were identified for each case. Images were reviewed and assessed for sonographically suspicious criteria guided by TI-RADS. Logistic regression was applied to determine if any sonographic features were associated with neoplasia. Odds ratios with 95% confidence intervals were calculated. Results Of 293 samples, 14 (4.7%) were neoplastic. Having no suspicious features conferred an average risk of 0.0339 (95% confidence interval: 0.02831-0.04087) of neoplasia. Risk of neoplasm significantly increased by having 1 and >1 suspicious feature ( P Conclusion Ultrasound can be used to estimate risk of neoplasia in MNG. In the absence of suspicious radiological findings, follow-up with ultrasound rather than FNAB may be appropriate in patients who have a low clinical suspicion for neoplasia.
The research of evaluation index system considering the capacity of multi-time scale power grid accepting renewable energy

Wind power and solar energy are representatives of renewable resources, and their volatility and randomization make power grid regard wind power and solar energy as negative load in daily dispatch. The increase of wind power and solar energy in the system may lead to the increase of uncontrollable factors, so the abilities for power grid to receive wind power and solar energy might be limited. Limiting factors including power grid's peak-load regulation capacity, frequency regulation capacity, wind power and solar energy output characteristics, load characteristics, external transmission channel of power network and so forth, setting up renewable resources index that the power grid can shoulder can reflect the "saturation level" of power grid, providing reference and evaluation basis for the operation and management of electric system. According to various kinds of factors that may affect power grid's acceptance ability, the index system which can reflect multi-time scale power grid's acceptance ability about renewable resources put forward. The power grid's acceptance ability is evaluated by power grid's short term, mid-term and long term these three time dimensions, and the operation security of the system and the restriction of the economy can also be took into consideration. Through index quantization value the power grid's acceptance ability towards different proportion's renewable resources can be reflected.
A phase I study of anti-inflammatory therapy with rilonacept in adolescents and adults with type 1 diabetes mellitus.

BACKGROUND The innate immune system may be activated around the time of diagnosis of type 1 diabetes (T1D). Components of this system, including cytokines such as interleukin-1β (IL-1β) represent potential therapeutic targets for disease modifying therapy. OBJECTIVE We conducted a phase 1 trial of rilonacept, an IL-1 cytokine trap, in patients with T1D. SUBJECTS AND METHODS Thirteen T1D patients (10 males) with median age (interquartile range, IQR) of 17 years (16-18), a median (IQR) of 5 months (5-7) since diagnosis. Rilonacept was administered subcutaneously for 26 weeks. Incidence of infections was the primary end-point. RESULTS There were 85 adverse events; 13 were Grade 2, of which 9 (8 infectious) were judged "possibly related" to the drug. The mean (SD) C-peptide on 2-hour mixed meal tolerance tests decreased from 0.87 (0.42) to 0.59 (0.29) ng/mL (P = .01 by paired t test) during 6 months on treatment. Hemoglobin A1c (HbA1c) increased from 6.8 (1.1) to 7.3 (1.1) (P = .05), but there was not a significant change in daily insulin dose (0.41 ± 0.23 to 0.47 ± 0.18), or in insulin dose-adjusted HbA1c (IDAA1c, 8.4 ± 1.8 to 9.0 ± 1.5). Subjects in "remission," defined as HbA1c <6.5 and a total daily insulin dose <0.5 units/kg/24 h, decreased from 5 to 4. There were no significantly differentially expressed genes in peripheral blood leukocytes before and after rilonacept. CONCLUSIONS Rilonacept treatment for 6 months is well-tolerated in individuals with T1D of recent onset, but is unlikely to be efficacious as a single agent in preserving beta cell function.
Biofilm formation on tracheostomy tubes.

An increased awareness of biofilms and their mechanisms has led to a better understanding of bacterial infections that occur following the placement of tracheostomy tubes and other implanted device...
How to deal with moral issues in group therapy without being judgmental.

The author discusses the pervasive difficulty psychotherapists seem to have in discussing patient morality, relating it to the fear of imposing (and feeling) shame and guilt. A way of nonjudgmental...
Why the Real Property Tax? A Fiscal System’s Approach

This chapter starts with a fiscal system’s approach to taxation and explains why the real property tax should be an inherent part of a tax system. Then it reviews the evolution of taxation in China before and after 1949 as a contrast and describes China’s financial reforms since 1978 as forerunners of subsequent socio-economic reforms. It depicts adopting the real property tax as a reshuffling of China’s current intergovernmental fiscal relations, not merely the introduction of a new tax. To vividly describe the challenges China faces in adopting the real property tax, it uses an analogy of the “window paper effect,” with the connotation that though the window paper is sturdy enough to resist winds, once the paper is broken purposely or a crack occurs, the removal of the whole window paper takes no huge efforts. This analogy of resistance losing steam will be used as a hidden line throughout the book as our expectation for future development.
The Conditions for Ethical Application of Restraints

Despite the lack of evidence for the effectiveness of physical restraints, their use in patients is widespread. The best ethical justification for restraining patients is that it prevents them from harming themselves. We argue that even if the empirical evidence supported their effectiveness in achieving this aim, the use of restraints would nevertheless be unethical, so long as well-known exceptions to informed consent fail to apply. Specifically, we argue that ethically justifiable restraint use demands certain necessary and sufficient conditions. These conditions are that the physician obtained informed consent for their application, that their application be medically appropriate, and that restraints be the least liberty-restricting way of achieving the intended benefit. It is a further question whether their application is ever medically appropriate, given the dearth of evidence for their effectiveness.
Brief Report: Impact of PrEP Training for Family Planning Providers on HIV Prevention Counseling and Patient Interest in PrEP in Atlanta, Georgia.

AbstractBackground:Safety net family planning clinics provide vital care for women in high HIV burden areas and may be ideal PrEP delivery sites. Yet, many family planning providers lack knowledge about PrEP.Setting:Four safety net family planning clinics in Atlanta, Georgia.Methods:We provided a 1.
Black opera: history, power, engagement

In her book, Black Opera: History, Power, Engagement, Naomi Andre presents a compelling argument that crosses traditional disciplinary boundaries, incorporating new ways of analysis that help shape...
A Theoretical Literature Review on the Social Identity Model of Organizational Leadership

The ProblemLeadership is commonly represented as being an individual construct with characteristics, competencies, and traits that identify the individual. Leadership development interventions are ...
Serum Endocannabinoid Levels in Patients With End-Stage Renal Disease

Author(s): Moradi, Hamid; Park, Christina; Igarashi, Miki; Streja, Elani; Argueta, Donovan A; Soohoo, Melissa; Daglian, Jennifer; You, Amy S; Rhee, Connie M; Kashyap, Moti L; DiPatrizio, Nicholas V; Vaziri, Nosratola D; Kalantar-Zadeh, Kamyar; Piomelli, Daniele | Abstract: Context:Previous studies have shown that the endocannabinoid system plays a major role in energy metabolism through the actions of its main mediators, 2-arachidonoyl-sn-glycerol (2-AG) and anandamide (AEA). Objective:We examined serum levels of major endocannabinoid mediators and their association with clinical parameters in patients with end-stage renal disease (ESRD). Design and Setting:Serum concentrations of 2-AG and AEA were measured in patients on maintenance hemodialysis (MHD) and controls, and correlations with various clinical and laboratory indices were examined. 2-AG was also measured in age and sex-matched healthy subjects for comparison of levels in patients undergoing MHD. Main Outcome Measure:Serum 2-AG. Results:Serum 2-AG levels were significantly elevated in patients with ESRD compared with healthy controls. Higher levels of 2-AG were found in patients on MHD compared to healthy subjects, and similar findings were seen in a second set of subjects in independent analyses. Among 96 patients on MHD, 2-AG levels correlated significantly and positively with serum triglycerides (ρ = 0.43; P l 0.0001), body mass index (ρ = 0.40; P l 0.0001), and body anthropometric measures and negatively with serum high-density lipoprotein cholesterol (ρ = -0.33; P = 0.001) following adjustment for demographic and clinical variables. Conclusions:In patients on MHD, levels of serum 2-AG, a major endocannabinoid mediator, were increased. In addition, increasing serum 2-AG levels correlated with increased serum triglycerides and markers of body mass. Future studies will need to evaluate the potential mechanisms responsible for these findings.
A Genome-Wide Analysis of Variants Influencing Methotrexate Clearance Replicates SLCO1B1.

Abstract 2466 High-dose methotrexate (HDMTX) is an important element of chemotherapy for acute lymphoblastic leukemia (ALL) and other malignancies. Methotrexate clearance influences cure and toxicity in children with acute lymphoblastic leukemia (ALL). HDMTX schedules and doses vary widely among treatment protocols. The Children9s Oncology Group (COG) tested the efficacy of 6 courses of 2 g/m 2 over 4 hours versus 1 g/m 2 over 24 hours (P9904 and P9905 protocols). Patients were assigned to one of four arms for consolidation: A, 24-hour methotrexate infusion (1 g/m 2 ) and no delayed intensification (DI); B, 4-hour methotrexate infusion (2 g/m 2 ) with no DI; C, 24-hour methotrexate infusion with DI; D, 4-hour methotrexate infusion with DI. We estimated methotrexate clearance for 1279 patients treated on these protocols, with two plasma MTX concentrations per course, using a Bayesian pharmacokinetic modeling approach. Germline genetic variation was assessed using the Affymetrix 6.0 array, and other single nucleotide polymorphisms (SNPs) were imputed based on 1000 Genomes reference data, yielding 5.2 million SNP genotypes evaluable per patient. Average MTX clearance was highly variable, with a median (range) of 164 (65–355) and 109 (49–290) ml/min/m 2 for the 24-hour and 4-hour infusions, respectively. Methotrexate clearance was lower in older children (p = 7 × 10 −7 ), girls (p = 2.7 × 10 −4 ), and patients who received a delayed intensification phase during consolidation (p = 0.0022). Adjusting for age, gender, race, and treatment arm, a genome-wide analysis showed that methotrexate clearance was associated with polymorphisms in SLCO1B1 (p = 2.1 × 10 −11 ), a gene that encodes for an organic anion transporter that is known to transport methotrexate. This replicates our previous findings (Trevino et al, J Clin Oncol. 2009;27(35):5972-8) that polymorphisms in SLCO1B1 influence methotrexate clearance in ALL patients treated on St. Jude protocols with three different HDMTX schedules. In a combined meta-analysis including the 1279 COG patients and 699 St. Jude patients, and adjusting for age, gender, race, and treatment arm, the association of methotrexate clearance with SLCO1B1 SNP rs4149056 yields a p-value of 3.1 × 10 −19 (Figure). Even after adjustment for the rs4149056 SNP, other polymorphisms in SLCO1B1 remained significantly related to methotrexate clearance, indicating that there are multiple variants in SLCO1B1 that can influence methotrexate clearance. Validation of the association of this gene with five different treatment regimens of methotrexate solidifies the robustness of this pharmacogenomic determinant of methotrexate clearance. Disclosures: No relevant conflicts of interest to declare.
Disordered Eating, Body Dissatisfaction, and Psychological Distress in Patients with Inflammatory Bowel Disease (IBD)

Little is known about eating attitudes and behaviors in patients with inflammatory bowel disease (IBD). The aim of this study was to explore the extent of disordered eating behaviors in a sample of patients with IBD and the association between demographic and disease-related variables and disordered eating. One hundred nine adults completed questionnaires during an outpatient visit to an academic IBD center. Questionnaires included demographic and disease characteristics, the eating attitudes test (EAT-26), the Body Image Scale, and the Brief Symptom Inventory. On the EAT-26, 13% of patients met the screening cutoff whereby further evaluation for an eating disorder is recommended, and 81% of patients responded affirmatively to at least one item determined by study investigators to represent pathological eating attitudes. Elevated scores on the EAT-26 were associated with being female, underweight, having IBD diagnosed during childhood, psychological distress and body image disturbance. These findings indicate that many patients with IBD may struggle with maladaptive attitudes toward eating.
A Cybersecurity Insurance Model for Power System Reliability Considering Optimal Defense Resource Allocation

With the increasing application of Information and Communication Technologies (ICTs), cyberattacks have become more prevalent against Cyber-Physical Systems (CPSs) such as the modern power grids. Various methods have been proposed to model the cybersecurity threats, but so far limited studies have been focused on the defensive strategies subject to the limited security budget. In this paper, the power supply reliability is evaluated considering the strategic allocation of defense resources. Specifically, the optimal mixed strategies are formulated by the Stackelberg Security Game (SSG) to allocate the defense resources on multiple targets subject to cyberattacks. The cyberattacks against the intrusion-tolerant Supervisory Control and Data Acquisition (SCADA) system are mathematically modeled by Semi-Markov Process (SMP) kernel. The intrusion tolerance capability of the SCADA system provides buffered residence time before the substation failure to enhance the network robustness against cyberattacks. Case studies of the cyberattack scenarios are carried out to demonstrate the intrusion tolerance capability. Depending on the defense resource allocation scheme, the intrusion-tolerant SCADA system possesses varying degrees of self-healing capability to restore to the good state and prevent the substations from failure. If more defense resources are invested on the substations, the intrusion tolerant capability can be further enhanced for protecting the substations. Finally, the actuarial insurance principle is designed to estimate transmission companies’ individual premiums considering correlated cybersecurity risks. The proposed insurance premium principle is designed to provide incentive for investments on enhancing the intrusion tolerance capability, which is verified by the results of case studies.
Activation of the Erk/MAPK signaling pathway is a driver for cadmium induced prostate cancer.

Abstract Purpose Cadmium (Cd) is reported to be associated with carcinogenesis. The molecular mechanisms associated with Cd-induced prostate cancer (PCa) remain elusive. Materials and methods RWPE1, PWR1E and DU 145 cells were used. RT2 Profiler Array, real-time-quantitative-PCR, immunofluorescence, cell cycle, apoptosis, proliferation and colony formation assays along with Gene Set Enrichment Analysis (GSEA) were performed. Result Chronic Cd exposure of non-malignant RWPE1 and PWR1E cells promoted cell survival, proliferation and colony formation with inhibition of apoptosis. Even a two-week Cd exposure of PCa cell line (DU 145) significantly increased the proliferation and decreased apoptosis. RT2 profiler array of 84 genes involved in the Erk/MAPK pathway revealed induction of gene expression in Cd-RWPE1 cells compared to RWPE1. This was confirmed by individual TaqMan gene expression analysis in both Cd-RWPE1 and Cd-PWR1E cell lines. GSEA showed an enrichment of the Erk/MAPK pathway along with other pathways such as KEGG-ERBB, KEGG-Cell Cycle, KEGG-VEGF, KEGG-Pathways in cancer and KEGG-prostate cancer pathway. We randomly selected upregulated genes from Erk/MAPK pathway and performed profile analysis in a PCa data set from the TCGA/GDC data base. We observed upregulation of these genes in PCa compared to normal samples. An increase in phosphorylation of the Erk1/2 and Mek1/2 was observed in Cd-RWPE1 and Cd-PWR1E cells compared to parental cells, confirming that Cd-exposure induces activation of the Erk/MAPK pathway. Conclusion This study demonstrates that Erk/MAPK signaling is a major pathway involved in Cd-induced malignant transformation of normal prostate cells. Understanding these dominant oncogenic pathways may help develop optimal therapeutic strategies for PCa.
Comparative analysis of snowfall accumulation over Antarctica in light of Ice discharge and gravity observations from space

The remote and cold Antarctic continent presents unique challenges to quantify precipitation rates from space and in situ observations. This has resulted in large uncertainties in current estimates. In this study, we quantify annual precipitation rates over seven Antarctic basins using a novel mass budget (MB) approach, by building on the recent Landsat based estimate of ice discharge and changes in total water storage from GRACE. The MB precipitation rates are compared with those from CloudSat, GPCP, the Arthern precipitation climatology, the GPM constellation sensors, a few popular reanalysis products, and a regional climate model for two periods: 2007-2010 and 2013-2015. The new estimates are bounded by CloudSat precipitation rates with and without adjustment for the unmeasured near surface precipitation. GPM products significantly underestimate Antarctic precipitation rate, but capture spatial variability that is valuable for bias-adjustment. We find variable performance between products at basin scale, suggesting that an in-depth regional study of precipitation rates is necessary.
Information Management Challenges and the Adverse Consequences of Using Reverse Auctions

Abstract Using reverse auctions (RAs) requires managing complex information. Yet, such challenges are not well understood and are often even underestimated. To address this knowledge gap, I conducted a Delphi study and follow-up interviews to identify information management challenges and the adverse consequences. Drawing on the agency theory and the garbage can theory, I developed three dimensions of information management challenges, advanced a theoretical model, and formulated propositions to suggest the adverse consequences. My findings suggest that deficiency, violation, and anarchy of information can result in procedural failure, financial and competitive loss to suppliers, and damage to buyer–supplier relationships.
Machine learning in experimental materials chemistry

Abstract The development of advanced materials is an important aspect of modern life. However, the discovery of novel materials involves searching the vast chemical space to find materials with desired properties. Recent developments in the applications of Machine Learning (ML) in materials chemistry show promise to accelerate the material discovery process. In this perspective article, we highlight the importance of ML in materials chemistry. We discuss few examples of ML applications in synthesis, characterization, and predicting activities of materials. Finally, we discuss the challenges in this field and how the progress in ML in chemistry is leveraged together with advanced robotics to perform automated optimization of material discovery.
Time-resolved, single-ended laser absorption thermometry and H2O, CO2, and CO speciation in a H2/C2H4-fueled rotating detonation engine

Abstract Rotating detonation engines (RDEs) require novel diagnostic tools to better understand complex detonation behavior and improve performance. To this end, a single-ended laser absorption sensor for in situ, time-resolved measurements of temperature, H2O, CO2, and CO concentrations has been developed and deployed within the annulus of a hydrogen/ethylene/air-fed RDE. With a measurement rate of 44 kS/s, the sensor delivers four co-aligned, mid-infrared laser beams into the annular detonation chamber and captures the back-reflected radiation through a single optical port. A ray-tracing optimization algorithm, designed to maximize signal-to-noise ratio and beam-perturbation tolerance, was used to determine the optimal sensor optical configuration. Wavelength-modulation spectroscopy (WMS) further compensated for interference sources in the harsh detonation environment. Time-resolved and time-averaged sensor measurements of gas temperature and species at equivalence ratios of 0.74, 0.87, and 1.03 are presented.
TiO2 nano-particle-dispersed polyimide composite optical waveguide materials through reverse micelles

Optically transparent polyimide : titanium dioxide (TiO2) composite waveguide materials were prepared by the dispersion of nano-sized TiO2 particles into polyimide. The particles were produced through reverse micelles using the sol–gel method, and were dispersed into the fluorinated polyimide solution. The solution was coated on a glass substrate, and a polyimide : TiO2 composite waveguide (4 wt% TiO2 concentration) was successfully produced after the heat treatment. Because the particle size was very small, no noticeable scattering loss was observed in the resultant slab waveguide. The measured optical propagation loss at 633 nm was 1.4 dB cm-1. It is equivalent to that of the pure polyimide, and the refractive index was increased from 1.550 to 1.560 by the incorporation.
From high temperature superconductivity to quantum spin liquid: progress in strong correlation physics

This review gives a rather general discussion of high temperature superconductors as an example of a strongly correlated material. The argument is made that in view of the many examples of unconventional superconductors discovered in the past twenty years, we should no longer be surprised that superconductivity emerges as a highly competitive ground state in systems where Coulomb repulsion plays a dominant role. The physics of the cuprates is discussed, emphasizing the unusual pseudogap phase in the underdoped region. It is argued that the resonating valence bond picture, as formulated using gauge theory with fermionic and bosonic matter fields, gives an adequate physical understanding, even though many details are beyond the powers of current calculational tools. The recent discovery of quantum oscillations in a high magnetic field is discussed in this context. Meanwhile, the problem of the quantum spin liquid (a spin system with antiferromagnetic coupling which refuses to order even at zero temperature) is a somewhat simpler version of the high Tc problem where significant progress has been made recently. It is understood that the existence of matter fields can lead to deconfinement of the U(1) gauge theory in 2 + 1 dimensions, and novel new particles (called fractionalized particles), such as fermionic spinons which carry spin and no charge, and gapless gauge bosons can emerge to create a new critical state at low energies. We even have a couple of real materials where such a scenario may be realized experimentally. The paper ends with answers to questions such as: What limits Tc if pairing is driven by an electronic energy scale? Why is the high Tc problem hard? Why is there no consensus? And why is the high Tc problem important?
Methylprednisolone, dexamethasone or hydrocortisone for acute severe pediatric asthma: does it matter?

Various intravenous (IV) corticosteroids are available for acute severe asthma (ASA) treatment. The choice of IV corticosteroids varies broadly and depends on institution, country, or physician pre...
Developing and Supporting Critically Reflective Teachers

Given the changing demographics and political landscape of US PK-12 education especially since the beginning of the twenty-first century, there is a great moral imperative to develop and support critically reflective teachers who will be able to survive and thrive in a contested sociopolitical climate. Arguably one of the most urgent issues confronting US PK-12 education is the widespread public perception that those who are involved with the education of children and youth are not responding to the needs of an increasingly diverse student population.
Preoperative Biopsy in Patients with Retroperitoneal Sarcoma: Usage and Outcomes in a National Cohort

Preoperative biopsy (PBx) is often recommended for retroperitoneal sarcoma (RPS), but its utilization rate and impact on perioperative management and outcomes remains undefined. Using the National Cancer Database, patients who underwent resection of non-metastatic RPS were identified (2006–2014). Patients who did and did not undergo PBx of the primary tumor were compared using propensity matching, and factors associated with survival were assessed by multivariable analysis. Of 2620 patients, 1110 (42.4%) underwent PBx. Factors significantly associated with performance of PBx included male sex [odds ratio (OR) 1.2, P = 0.035], tumor size ≤ 5 cm (OR 1.5, P = 0.012), tumor size > 5 to ≤ 10 cm (OR 1.3, P = 0.009), non-well-differentiated liposarcoma histology (OR 2.0, P ≤ 0.001), and treatment at a high-volume center (OR 1.3, P = 0.021). Receipt of PBx was significantly associated with administration of neoadjuvant radiation (OR 8.8, P < 0.001) or systemic therapy (OR 3.3, P < 0.001), radical surgical resection (OR 1.6, P < 0.001), and complete tumor resection (OR 1.5, P < 0.003). Neoadjuvant radiation [hazard ratio (HR) 0.7, P = 0.003] and complete tumor resection (HR 0.6, P < 0.001) were significantly associated with improved overall survival (OS). Performance of PBx was not associated with OS (HR 1.1, P = 0.070), and following propensity matching, 5-year OS did not differ between the two groups (56.5% PBx vs 58.4% no PBx, P = 0.247). A minority of patients with non-metastatic RPS undergo PBx. PBx does not negatively impact survival, but may indirectly improve outcomes in select patients by virtue of receipt of neoadjuvant therapy and attainment of complete tumor resection.
The Effect of Modafinil on the Safety and Pharmacokinetics of Lorlatinib: A Phase I Study in Healthy Participants.

Lorlatinib is a third-generation tyrosine kinase inhibitor approved for the second-line treatment of patients with advanced anaplastic lymphoma kinase-positive non-small cell lung cancer. Lorlatinib is metabolized by cytochrome P450 (CYP) 3A and contraindicated with strong CYP3A inducers because of significant transaminase elevation. This phase I, open-label, two-period study evaluated the impact of a moderate CYP3A inducer, modafinil, on the safety and pharmacokinetics of lorlatinib. Healthy participants received single-dose oral lorlatinib (50 mg [n = 2], 75 mg [n = 2], or 100 mg [n = 2 + 10 in an expanded cohort]) in Period 1 followed by modafinil 400 mg/day (days 1–19) and single-dose lorlatinib (day 15, same dose as previous) both orally in Period 2. Blood samples were collected for 120 h after each dose of lorlatinib. Of 16 participants, ten completed the study; six participants, all in the expanded 100-mg cohort, discontinued because of adverse events during the modafinil lead-in dosing period. Single doses of lorlatinib 50–100 mg were well tolerated when administered alone and in the presence of steady-state modafinil. Of the ten participants who completed the study, all had transaminase values within normal limits during the combination of lorlatinib with modafinil. The ratios of the adjusted geometric means (90% confidence interval) for lorlatinib area under the plasma concentration–time profile extrapolated to infinity and maximum plasma concentration were 76.69% (70.15–83.83%) and 77.78% (65.92–91.77), respectively, when lorlatinib 100 mg was co-administered with steady-state modafinil compared with lorlatinib administration alone. Lorlatinib 100 mg may be safely co-administered with moderate CYP3A inducers. ClinicalTrials.gov NCT03961997; registered 23 May, 2019.
Group Identity and Agency Frictions : Evidence using Big Data

This paper examines whether similarity in social identities between a manager and the board affects executive compensation, firm value, and agency frictions. By using a novel dataset on surnames with multiple identities (native language, native place, and caste), developed by merging micro census data of 474 million Indians with Linguistic Survey of India (LSI) data, I provide evidence that the firms with a shared group identity between a manager and the board do well compare to other firms and due to in-group favoritism, managers of such firms earn higher compensation. These results are stronger for group identity based on native language and native place. I also find that the firm benefits from taking on the cost of in-group favoritism as it reduces the agency frictions and increases firm value in the long run. These results are robust to the endogeneity test, managerial influence on firm, college ties, ties from past employment, and various other checks.
Bisphosphonates, Bone and Joint Pain

Bisphosphonates (BPs) have an established role in a number of diseases including osteoporosis, but the role of BPs for treating symptomatic conditions other than bone metastases is less clear. We review recent data on the efficacy of BPs in the treatment of symptomatic bone and joint pain with osteoarthritis (OA) as an example. Although controversial, BPs have been reported to improve pain ratings, imaging features, and inflammatory markers in patients with arthritis, more specifically OA. It is possible that their effects in periarticular bone strongly influence the complex inflammatory process within the joints. Recent data also suggests that they can potentially impact synovial and synoviocytes and macrophages. Although more studies are needed to define their contribution in clinical practice, increasing evidence suggests they hold an important function, especially in conditions with periarticular bone involvement such as OA. Although BPs are indicated primarily for prevention and treatment of osteoporosis, they can also have potential effects on the inflammatory process of other conditions, including OA. Improvements in pain scale ratings, periarticular findings through imaging, and inflammatory response suggest their potential extra-osteoporotic properties.
Comparison of myeloid neoplasms with nonclassic 3q26.2/MECOM versus classic inv(3)/t(3;3) rearrangements reveals diverse clinicopathologic features, genetic profiles, and molecular mechanisms of MECOM activation.

MECOM rearrangements are recurrent in myeloid neoplasms and associated with poor prognosis. However, only inv(3)(q21q26.2) and t(3;3)(q21;q26.2), the classic MECOM rearrangements resulting in RPN1-MECOM rearrangement with Mecom overexpression and GATA2 haploinsufficiency, define the distinct subtype of acute myeloid leukemia (AML) and serve as presumptive evidence for myelodysplastic syndrome based on the current World Health Organization classification. Myeloid neoplasms with non-classic 3q26.2/MECOM rearrangements have been found to be clinically aggressive, but comparative analysis of clinicopathologic and genomic features is limited. We retrospectively studied cohorts of myeloid neoplasms with classic and non-classic MECOM rearrangements. Cases with classic rearrangements consisted predominantly of AML, often with inv(3) or t(3;3) as the sole chromosome abnormality, whereas the group of non-classic rearrangements included a variety of myeloid neoplasms, often with complex karyotype without TP53 mutations and similarly dismal overall survival. Immunohistochemistry revealed Mecom protein overexpression in both groups, but overexpression in cases with non-classic rearrangements was mediated through mechanism other than GATA2 distal enhancer involvement typical for classic rearrangement. Our results demonstrated that myeloid neoplasms with non-classic 3q26.2/MECOM rearrangements encompass a diverse group of diseases with poor clinical outcome, overexpression of Mecom protein as result of non-classic mechanism of MECOM activation. This article is protected by copyright. All rights reserved.
Predicting Group Choice: an Experimental Study Using Conjoint Analysis

Group decision making occurs in a variety of contexts. Yet there are limited studies that attempt to predict group choices as a function of individual preferences. This study examines the usefulness of conjoint analysis in the prediction process. An actual experiment was conducted in which both individual and group choices were determined. The results show that Conjoint Analysis may be a fruitful way of predicting group preferences.
How to make icons useful

Human use of images for purposes of communication is nothing new. Stone age artists were painting them on the walls of their caves as long as 20,000 years ago. Nor is the use of images as coding elements in formal orthographic systems anything new - that dates back at least 5,000 years. The push to "internationalize" communications media and the relatively recent development of graphic user interfaces, however, has spawned, it seems, a mad rush to abandon more highly evolved and sound-based orthographies in favor of image-based writing systems, or, in some instances, simply images. The article that follows examines the use of icons as visual labels, discusses their strengths and weaknesses, and suggest guidelines for their design and use.
Posttranscriptional regulation of a class of human cytomegalovirus phosphoproteins encoded by an early transcription unit.

Abstract We have further characterized and determined the origins of a family of nuclear phosphoproteins of 84, 50, 43, and 34 kilodaltons (kDa) encoded by a class of early transcripts arising from the adjacent EcoRI fragments R and d (map units 0.682 to 0.713) of the strain AD169 human cytomegalovirus genome. These RNAs have a complex spliced structure with common 5' and internal exons and alternative 3' exons with coterminal 3' ends. At early times, two fully processed species of 2.1 and 2.2 kilobases (kb) predominated. As the infection progressed to late times, there was a decrease in splicing of the RNA, generating larger transcripts 2.5 to 2.65 kb in size, which corresponded to the species which had spliced out only the first intron, as well as the completely unspliced transcript. We previously reported that the 34-kDa protein could be derived from a transcript which had failed to splice out the first intron (D. A. Wright, S. I. Staprans, and D. H. Spector, J. Virol. 62:331-340, 1988), but the origin of the other proteins was unclear. cDNA cloning has shown that the 2.1-, 2.2-, and 2.5-kb RNAs encode the 50-, 43-, and 84-kDa proteins, respectively. The shift in the splicing pattern of these RNAs with time revealed a posttranscriptional control mechanism which results in the differential accumulation of individual proteins within this family of nuclear phosphoproteins. Expression of the 84-, 43-, and 34-kDa proteins correlated well with the steady-state concentrations of their respective mRNAs. The 50-kDa protein, however, was not expressed in abundance until late times, despite the presence of the 2.1-kb mRNA in the cytoplasm at early times, suggesting a secondary level of posttranscriptional regulation for this protein. Full expression of the RNAs and proteins was dependent on continuing viral DNA synthesis. Accumulation of the 50-kDa protein was found to be particularly sensitive to the state of viral DNA replication and could not be detected after inhibition of replication. Further analysis of these proteins revealed that each one had a unique pattern of serine phosphorylation. Although there was one common site of phosphorylation, most likely located within the amino-terminal shared region, even this site showed quantitative differences in the level of phosphorylation for each of the proteins. Analysis of the Towne strain and two recent independent clinical isolates of human cytomegalovirus has shown that this family of proteins is highly conserved among human cytomegaloviruses.
Group Counseling for Codependence

Currently there exists a proliferation of self-help literature on codependence and a lack of scientific inquiry on this topic. This paper examines the use of group counseling with self-identified codependent individuals. Following 16 weeks of group treatment, participants changed significantly on a measure of codependence, the Spann-Fischer Codependence Scale (Fischer, Spann, & Crawford, 1991), and on four personality scales from the Millon Cliical Multiaxial Inventory-I1 (Millon. 1987). These preliminary results indicate that group counseling appears to reduce dependence. Also the Spann-Fischer Codependence Scale appears to assess codependence adequately and could be used with caution in pychotherapeutic practice.
Tissue Glutathione as a Cyst(e)ine Reservoir during Fasting and Refeeding of Rats

Previous reports suggest that liver glutathione serves as a cyst(e)ine reservoir in both starved rats and rats fed a cyst(e)ine-deficient diet. We investigated whether glutathione concentrations in other tissues also decrease and whether component amino acids of glutathione increase under such conditions. Tissue glutathione and free amino acid concentrations were measured in six groups of growing rats (120-150 g; four animals/group) during fasting and refeeding regimens. All animals were fed a rat stock diet ad libitum for 5 days. Two groups were than fasted for 24 or 48 hours, respectively. Other groups were fasted for 48 hours and then refed for 10, 24 or 48 hours respectively the stock diet. Significant changes (P less than or equal to 0.05) in liver and intestine glutathione concentrations were noted with 24 and 48-hour fasting, and a 24-hour refeeding was necessary to return concentrations to prefasting values. Muscle glutathione concentrations decreased slightly with fasting, but remained low with refeeding. Erythrocyte glutathione concentrations were independent of dietary treatment. Liver cysteine and glycine concentrations increased after 24 hours' fasting, but glutamate levels were not affected. The data indicate that liver and intestine glutathione serve as cyst(e)ine reservoirs during fasting. Since erythrocyte and muscle glutathione levels did not decrease, levels in these tissues cannot be used to measure cyst(e)ine status in premature infants fed parenterally.
The flatness and sudden evolution of the intergalactic ionizing background

Author(s): Munoz, Joseph A; Oh, S Peng; Davies, Frederick B; Furlanetto, Steven R | Abstract: The ionizing background of cosmic hydrogen is an important probe of the sources and absorbers of ionizing radiation in the post-reionization universe. Previous studies show that the ionization rate should be very sensitive to changes in the source population: as the emissivity rises, absorbers shrink in size, increasing the ionizing mean free path and, hence, the ionizing background. By contrast, observations of the ionizing background find a very flat evolution from z~2-5, before falling precipitously at z~6. We resolve this puzzling discrepancy by pointing out that, at z~2-5, optically thick absorbers are associated with the same collapsed halos that host ionizing sources. Thus, an increasing abundance of galaxies is compensated for by a corresponding increase in the absorber population, which moderates the instability in the ionizing background. However, by z~5-6, gas outside of halos dominates the absorption, the coupling between sources and absorbers is lost, and the ionizing background evolves rapidly. Our halo based model reproduces observations of the ionizing background, its flatness and sudden decline, as well as the redshift evolution of the ionizing mean free path. Our work suggests that, through much of their history, both star formation and photoelectric opacity in the universe track halo growth.
Early initiation of low-level parenteral dextrose induces an accelerated diabetic phenotype in septic C57BL/6J mice

Development of hyperglycemia during sepsis is associated with increased morbidity and mortality. Nutritional support is common practice in the intensive care unit, but the metabolic effects are not well understood. The purpose of this study is to determine the effect of early low-level calorie provision on the development of hyperglycemia in a clinically relevant murine model of sepsis. C57BL/6J mice underwent femoral arterial and venous catheterization followed by cecal ligation and puncture (CLP) or sham surgery and low-dose intravenous dextrose or saline infusion. Blood glucose, plasma insulin, and cytokines were measured after 24 h. Additional septic mice underwent hyperinsulinemic-euglycemic clamps or received intravenous insulin concurrent with dextrose to determine whole-body insulin sensitivity and test the efficacy of insulin to reverse hyperglycemia. Neither dextrose infusion nor CLP alone induced hyperglycemia. Early initiation of low-level dextrose in septic mice produced a variable glycemic response: 49% maintained euglycemia (blood glucose < 200) and 27% developed severe hyperglycemia (blood glucose ≥ 600). Hyperglycemia was associated with increased inflammation and reduced insulin secretion and sensitivity compared with control mice or CLP mice maintaining euglycemia. Insulin prevented the progression to severe hyperglycemia but was ineffective in reestablishing glycemic control once hyperglycemia had developed. In conclusion, early initiation of clinically relevant low-level dextrose (∼ 20% daily caloric requirements) precipitated hyperglycemia akin to an acute diabetic phenotype in septic mice characterized by decreased insulin sensitivity, decreased insulin secretion, and an increased inflammatory response.
Modification of age-induced changes in heme and hemoproteins by testosterone in male rats

Abstract Age-related changes in heme and hemoproteins, as well as the effect of testosterone treatment on these modifications were examined in male Sprague-Dawley rats. The activity of δ-aminolevulinic acid synthase (ALA-S) and the microsomal concentration of heme in aged rats were decreased by 37% and 33%, respectively, as compared to young values. In contrast, a marked increase in the activity of microsomal heme oxygenase (MHO) was seen in these animals. In aged rats, the level of cytochrome P -450 was decreased by 37%, as compared to young values. Furthermore, the activities of benzo[a]pyrene hydroxylase and aniline hydroxylase were decreased in proportion to the microsomal content of cytocyrome P -450. Steroid Δ 4 -hydrogenase, an index of endogenous substrate metabolism, exhibited no changes in activity during the aging process. The level of various hemoproteins such as cytochrome b 5 and tryptophan pyrrolase in aged animals remained unaltered despite the decreased hepatic concentration of heme. It is worth noting that testosterone treatment of aged castrated rats restored the level of heme and cytochrome P -450 and the altered enzymatic activities of ALA-S and MHO to the “young” condition. In view of these findings, it is concluded that the events which lead to the low level of heme and cytochrome P -450 and its dependent mixed function oxidase activity during the senescent period could be due to increased rates of MHO and diminished ALA-S activities in these animals.
Parental Response to Cystic Fibrosis: A Contextual Analysis of the Diagnosis Phase

A contextual framework guided the measurement of specific stressors encountered by parents of children recently diagnosed with cystic fibrosis (CF). Three variables were assessed within the context of the parenting role: illness-specific tasks, normal parenting tasks, and strains in family roles. These situation-specific stressors were contrasted with global measures of parenting stress in their ability to predict depression. Sixty-four parents (36 mothers, 28 fathers) of infants and toddlers recently diagnosed with CF completed a structured interview and standardized measures in the home. Parents reported elevations in both situation-specific and global parenting stress, and a greater number of depressive symptoms than a norm group. Mothers reported significantly greater strain in managing their caregiving role and higher levels of depression than fathers. Controlling for situation-specific parenting stress and marital satisfaction, regression analyses indicated that role strain related to CF was associated with greater depression in mothers, but not fathers. Furthermore, stressors measured contextually rather than globally accounted for substantially greater proportions of the variance in depression. The findings highlight the need to measure ongoing strains specific to the medical condition, and to assess role-related changes.
Phosphor Concentration Effects on Optothermal Characteristics of Phosphor Converted White Light-Emitting Diodes

The thermal and optical characteristics of phosphor converted white light-emitting diodes (LEDs) with different phosphor concentrations ranging from 4 wt % to 13 wt % are investigated. The light output of LEDs with higher phosphor concentration is found to have larger degradation in constant current compared with pulse current than that with lower phosphor concentration. In addition, the junction temperatures of phosphor converted white LEDs raise with increasing phosphor concentration, so that the decreased phosphor conversion efficiency is observed both in pulse and constant current modes. The physical mechanisms for these observations are discussed. This study elucidates the phosphor dependent optical and thermal behavior of phosphor converted white LEDs.
Diurnal variation in plasma ir-beta-endorphin levels and experimental pain thresholds in the horse

Diurnal variation in nociceptive sensitivity and plasma immunoreactive beta-endorphin (ir-BEND) concentrations was examined in eight healthy Thoroughbred horses. Pain thresholds, ir-BEND concentrations, rectal temperature, heart rate, respiratory rate and pupil diameter were measured over a 24 hour period. Nociceptive sensitivity was determined using two objective measures of pain: the skin-twitch reflex latency and the hoof withdrawal reflex latency. Significant variation in both nociceptive thresholds and ir-BEND concentrations were noted over the 24 hour period, with elevated pain thresholds observed at 0900 hours and smaller secondary peaks at 1500 hours. Immunoreactive beta-endorphin concentrations were also elevated at 0900 hours. Cardiac rate was high and pupil diameter was largest at 0900 hours. These physiologic changes, along with increased pain threshold, mimic the observed effects of morphine and other mu-agonists in the horse. The results of this study suggest that endogenous opioid peptides may modulate pain threshold as well as other physiologic parameters in the horse.