cssi/SciSciGPT-SciSciNet huggingface dataset:
Species-Dependent Variability of ADAMTS-13 Mediated Proteolysis of Human Recombinant von Willebrand Factor.

ADAMTS-13 is a plasma metalloprotease that regulates platelet adhesion and aggregation through cleavage of von Willebrand factor (VWF) multimers within the A2 domain between residues tyrosine 1605 and methionine 1606. Genetic (Upshaw-Schulman syndrome) and acquired severe functional defects of ADAMTS-13 are associated with the presence of non-proteolysed ultra-large VWF multimers. These multimers are the most thrombogenic form of this molecule and spontaneously bind to platelets causing thrombotic thrombocytopenic purpura (TTP), a syndrome characterized by microvascular thrombosis and platelet consumption. We investigated proteolysis of human rVWF by ADAMTS-13 present in plasma of different species typically used as preclinical animal models. Our substrate was a recombinant, Chinese hamster ovary (CHO) cell line-derived rVWF, processed to mature rVWF by exposure to rfurin and highly purified by a series of chromatography steps. Multimer analysis of rVWF shows absence of satellite bands consistent with intact subunits not cleaved by ADAMTS-13. rVWF was incubated with BaCl2-activated plasma samples from different species, 4 hours at 37°C with urea. ADAMTS-13-mediated degradation of VWF was measured by collagen binding (CB) assay and proteolysis visualized by high-resolution multimer analysis stained with a polyclonal anti-human VWF antibody and by non-reducing SDS-PAGE, followed by immunoblotting with a polyclonal anti-human VWF antibody. Incubation of rVWF with normal human plasma resulted in the loss of collagen binding activity and disappearance of high molecular weight multimers with simultaneous formation of the specific satellite bands leading to a multimeric pattern similar to pdVWF. In contrast, using the same amount of animal plasma (50 mU/ml human-equivalent concentration), differences were found in the ADAMTS-13 activity levels in terms of the degree of proteolytic degradation of rVWF multimers as follows as measured by CBA: Mouse plasma samples from wild type or from mice lacking FVIII and VWF, all with a C57BL/6J background, showed no ADAMTS-13 activity towards human rVWF. No activities were observed in rat and guinea pig plasma. Porcine plasma showed only minimal activity. Samples from monkey strains (baboon, rhesus and cynomolgus) and from beagle dogs showed medium activities with a residual CB of 60%. Rabbit plasma was as effective as human plasma in cleaving and degrading VWF resulting in a residual CB of 20%. The quantitative results were confirmed by multimer visualization. We conclude that animal plasma differs markedly in plasma ADAMTS-13 activity and capacity to cleave human VWF multimers. Our study confirms previous in vivo studies with human rVWF where no proteolysis was seen in mice, and little proteolysis was observed in dogs (Turecek et al., Blood 1997) and pigs (Roussi J et al. Blood.Coag.Fibrinol. 1998). The present study also suggests caution is needed in interpreting the (patho)physiology and metabolism of human VWF from animal models.
Laparoscopic debridement of hepatic necrosis after hepatic artery chemoembolization.

BACKGROUND AND OBJECTIVES Hepatic artery chemoembolization (HACE) used to treat neuroendocrine tumors metastatic to the liver has shown both survival benefit and improvement in symptoms. The development of hepatic necrosis after HACE is rare, but the consequences can be devastating. We report the first case of laparoscopic management of extensive hepatic necrosis occurring after HACE. CASE REPORT A 58-year-old man with neuroendocrine tumor metastatic to the liver underwent HACE in addition to medical management. He had undergone previous biliary stenting for biliary obstruction. After HACE was performed via the right hepatic artery, the patient developed sepsis due to right hepatic lobe infarction. Percutaneous drainage and antibiotics were attempted for 2 months, but hepatic debridement was ultimately required due to repeated drain malfunction and septic complications. Laparoscopic necrosectomy was performed with ease and with little blood loss. The patient quickly recovered without any further infectious complications. CONCLUSION Infected hepatic necrosis resulting from HACE that fails percutaneous management can be successfully managed with laparoscopic necrosectomy. This report adds to the growing evidence that minimally invasive techniques can be used to manage complicated hepatic conditions.
Mindful feeding and child dietary health

Abstract Objective This study examined the relationship between mindful feeding as a novel construct and parent-reported child dietary intake. Methods Participants (N = 497) were parents of children ages 2.9 to 7.5 recruited through Amazon Mechanical Turk (MTurk). Parents were primarily non-Hispanic white (79%) and female (76%). Simple and hierarchical regression analyses were conducted to examine the associations between parental mindful feeding (i.e., parent mental and emotional presence while feeding a child) and their children's dietary intake. Results Mindful feeding accounted for 5.1% of the unadjusted variance in child fruit and vegetable intake. Mindful feeding accounted for 4.2% of the unadjusted variance in child added sugar consumption after accounting for relevant covariates. Specifically, higher parental mindful feeding predicted higher fruit and vegetable intake and lower sugar intake among children. Conclusions Mindful feeding was associated with almost all indicators of healthier child diet, indicating great potential for this approach to improve child health. If incorporated into general or health-focused interventions for parents, mindfulness could significantly improve child health outcomes. Further development and validation of the Mindful Feeding Questionnaire is also recommended, as it could become a useful survey tool to assess for this construct.
Loop induced decays of the little Higgs: /H-->gg, /γγ

Abstract We analyze the loop induced decays of the Higgs boson into pairs of gluons and photons in the littlest Higgs model. We find that the deviation of the partial widths for these decays relative to their Standard Model values scales with 1/ f 2 , where f ∼ TeV is the mass scale of the new heavy particles in the model. For f =1 TeV, Γ ( H → gg ) is reduced by 5–10% and Γ ( H → γγ ) is modified by +10% to −20% compared to their Standard Model values. While the LHC and a linear e + e − collider would be sensitive to these deviations only for relatively low values of f ≲1 TeV, a photon collider could probe the deviation in Γ ( H → γγ ) up to f ≲1.8 (1.2) TeV at the 2 (5) σ level.
Fermentation substrates and economics.

Publisher Summary This chapter focuses on costs involved in fermentation processes. Depending on the fermentation, it appears that 25% to 70% of the total fermentation costs are because of the carbon source. At current prices of fermentable sugars and of other carbon sources derived from coal and petroleum, most ethanol and SCP fermentations cannot compete economically with synthetically or agriculturally derived equivalent commodities. Fermentation processes can compete with higher-value products for which the carbon source is likely to be an important, but not overwhelming, cost factor. Effective conversion of lignocellulosic materials holds great promise in providing low-cost sugar syrups for fermentation. Without such cellulose-derived sugar syrups, bulk commodity or chemicals production via fermentation is unlikely in the near future. Sophisticated separation and genetic engineering techniques will greatly assist the progress of biotechnology. However, the potential of many important fermentations will be severely limited in spite of such sophisticated technology, until equally sophisticated thinking and technology are applied to effective conversion of lignocellulosic materials.
The Relationship Between Nonsteroidal Anti-inflammatory Drug Use and Age-related Macular Degeneration

Purpose To describe the relationship between the incidence of age-related macular degeneration (AMD) and nonsteroidal anti-inflammatory drug (NSAIDs) use. Design Prospective cohort study. Methods This study consisted of participants in the California Men's Health Study. Those who completed surveys in 2002-2003 and 2006 were included. Men who self-reported use of aspirin, ibuprofen, naproxen, valdecoxib, celecoxib, and/or rofecoxib at least 3 days per week were considered NSAID users. Patients were categorized as non-users, former users, new users, or longer-term users based on survey responses. NSAID use was also categorized by type: any NSAIDs, aspirin, and/or non-aspirin NSAIDs. Age, race/ethnicity, smoking status, education, income, alcohol use, and Charlson comorbidity index score were included in the multivariate analysis as risk factors for AMD. Results A total of 51 371 men were included. Average follow-up time was 7.4 years. There were 292 (0.6%) and 1536 (3%) cases of exudative and nonexudative AMD, respectively. Longer-term use of any NSAID was associated with lower risk of exudative AMD (hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.50-0.96, P = .029). New users of any NSAIDs (HR = 0.79, 95% CI 0.68-0.93, P = .0039) and aspirin (HR = 0.82, 95% CI 0.70-0.97, P = .018) had a lower risk of nonexudative AMD, although this trend did not persist in longer-term users. The relationship between exudative or nonexudative AMD and the remaining categories of NSAID use were not significant. Conclusion The overall impact of NSAIDs on AMD incidence is small; however, the lower risk of exudative AMD in longer-term NSAID users may point to a protective effect and deserves further study as a possible mechanism to modulate disease risk.
Variation in the nulliparous, term, singleton, vertex cesarean delivery rate

Objective To estimate the contributions of patient and health care provider-hospital characteristics to the variation in the frequency of nulliparous, term, singleton, vertex cesarean delivery in a multi-institutional U.S. cohort. Methods We performed a secondary analysis of the multicenter Assessment of Perinatal Excellence cohort of 115,502 mother and neonatal pairs who were delivered at 25 hospitals between March 2008 and February 2011. Women met inclusion criteria if they were nulliparous and delivered a singleton in vertex presentation at term. Hospital ranks for nulliparous, term, singleton, vertex cesarean delivery frequency were determined after risk adjustment. The fraction of variation in nulliparous, term, singleton, vertex cesarean delivery frequency attributable to patient and health care provider-hospital characteristics was assessed using hierarchical logistic regression. Results Of the 115,502 deliveries in the initial cohort, 38,275 nulliparous, term, singleton, vertex deliveries met inclusion criteria. The median hospital nulliparous, term, singleton, vertex cesarean delivery frequency was 25.3% with a range from 15.0% to 35.2%. The majority of hospitals (16/25) changed rank quintiles after risk adjustment; overall the changes in rank were not statistically significant (P=.53). Patient characteristics accounted for 24% of the nulliparous, term, singleton, vertex cesarean delivery variation. The analyzed health care provider-hospital characteristics were not significantly associated with cesarean delivery frequency. Conclusion Although patient characteristics accounted for some of the variation in nulliparous, term, singleton, vertex cesarean delivery frequency and accounting for case mix had implications for hospital cesarean delivery rankings, the majority of the variation was not explained by the characteristics evaluated. These findings emphasize the importance of continued efforts to understand aspects of obstetric care, including case mix, that contribute to cesarean delivery variation.
Ophthalmic artery blood flow velocity increases during hypocapnia.

The effects of anesthetic management on blood flow to the optic nerve have not been well-studied. The ophthalmic artery provides the majority of the blood supply to the optic nerve via several smaller branches. Retinal blood flow has been shown to react to carbon dioxide (CO2) similar to intracranial vessels, but insufficient data exist for the ophthalmic artery. The purpose of this study is to examine the CO2-reactivity of the ophthalmic artery. Eight healthy awake subjects aged 28 to 50 yr were tested for CO2-reactivity in the ophthalmic artery using transcranial Doppler (TCD) insonation of blood flow velocity (Vop), while simultaneously recording the Vop of the middle cerebral artery (Vmca) as an internal control. Vop and Vmca recordings were made under hypocapnic, normocapnic and hypercapnic conditions. The CO2-reactivity slope of Vmca was 3.27% per mmHg PaCO2. From normocapnia to hypercapnia, Vop did not change significantly (mean ± SD, 18 ± 4 cm·sec−1 to 18 ± 6 cm·sec−1), (endtidal CO2, et CO2, = 43 ± 5 mmHg to 53 ± 4 mmHg, respectively). In contrast, Vop increased significantly under hypocapnic conditions (etCO2 = 26 ± 4 mmHg) to 25 ± 5 cm·sec−1 (P < 0.05). The CO2-reactivity slope of Vop from normocapnia to hypocapnia was 2.57% per mmHg. This study demonstrates that Vop increases with hypocapnia, but is unaffected by hypercapnia. The anastomoses of the ophthalmic artery with the external carotid artery, which displays a relatively fixed resistance, may account for these findings.
Video Demonstrations to Enhance Learning of Mechanics of Materials Inside and Outside the Classroom

Using video to present demonstrations holds a significant number of advantages, particularly when class size or demonstration complexity prevents students from having hands on access. In video format delivered via the web, students have the capability to pause and repeat videos. Used in a classroom setting, the video provides the instructor more ease in set up and ensures high quality viewing in a large lecture hall forum. We have created videos of mechanics of materials demonstrations from a collection used in both introductory and advanced mechanics of materials courses. A wide range of topics are represented in the video collection, but three topics in particular (thermal effects, transverse shear in bending, combined loading) have been identified for use teaching where an assessment of learning outcomes can be measured.
The Problem of Infertility

Infertility represents a major life crisis to more than 10 million people in the United States1—as individuals, as partners in marriage, and as members of families and society. Few people who have not been personally involved are fully aware of the emotional impact of recognition of the problem, the diagnostic and therapeutic procedures that may be undertaken, and the eventual outcome of such an investigation.
The impact of gratitude on adolescent materialism and generosity

Despite decades of research on materialism, there are few viable strategies for reducing materialism in younger consumers. In this paper, we present two studies conducted among over 900 adolescents...
Ingestion of subthreshold doses of environmental toxins induces ascending Parkinsonism in the rat.

Increasing evidence suggests that environmental neurotoxicants or misfolded α-synuclein generated by such neurotoxicants are transported from the gastrointestinal tract to the central nervous system via the vagus nerve, triggering degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and causing Parkinson’s disease (PD). We tested the hypothesis that gastric co-administration of subthreshold doses of lectins and paraquat can recreate the pathology and behavioral manifestations of PD in rats. A solution containing paraquat + lectin was administered daily for 7 days via gastric gavage, followed by testing for Parkinsonian behavior and gastric dysmotility. At the end of the experiment, brainstem and midbrain tissues were analyzed for the presence of misfolded α-synuclein and neuronal loss in the SNpc and in the dorsal motor nucleus of the vagus (DMV). Misfolded α-synuclein was found in DMV and SNpc neurons. A significant decrease in tyrosine hydroxylase positive dopaminergic neurons was noted in the SNpc, conversely there was no apparent loss of cholinergic neurons of the DMV. Nigrovagally-evoked gastric motility was impaired in treated rats prior to the onset of parkinsonism, the motor deficits of which were improved by l-dopa treatment. Vagotomy prevented the development of parkinsonian symptoms and constrained the appearance of misfolded α-synuclein to myenteric neurons. These data demonstrate that co-administration of subthreshold doses of paraquat and lectin induces progressive, l-dopa-responsive parkinsonism that is preceded by gastric dysmotility. This novel preclinical model of environmentally triggered PD provides functional support for Braak’s staging hypothesis of idiopathic PD.
Characterizing Sex-Specific Baseline Characteristics and Outcomes in Left Ventricular Assist Device (LVAD) Support

Purpose Women are underrepresented in the patient population who receive left ventricular assist devices (LVAD) as a therapy for advanced heart failure (HF). A limited number of studies suggest greater adverse outcomes in women on LVAD support than in men. This study aims to expand the sex-based data on the growing female LVAD population. Methods Single-center retrospective of 25 women and 126 men in their first 12 months of LVAD support were analyzed using IBM SPSS Statistics V. 24.0. Adverse events were categorized using the INTERMACS Appendix. Results The mean ages for female and male patients were 48.0 ± 18.0 and 57.0 ± 12.0 years, respectively (p = 0.002). Women were more likely to be listed for heart transplant prior to LVAD implantation (76% vs 54%, p = 0.042), the etiology of HF was more often non-ischemic in origin (79% vs 52%, p = 0.013) and Cr was lower (1.0 vs 1.4 mg/dL, p = 0.001). No other statistically significant differences existed at baseline between the two cohorts, including baseline NYHA class, INTERMACS status, BMI, type of LVAD device, or medications prior to implant. There were no significant differences in outcomes including readmission, bleeding, infection, neurological events, or right heart failure within the first year. Time to first neurological event was longer in women (7 months vs 2 months, p = 0.008). There was no difference in risk of death in the first year. Conclusion Although younger and non-ischemic, women with LVADs experience similar first year outcomes as men.
Polarimetric “Fingerprints” of Different Microphysical Processes in Clouds and Precipitation

Polarimetric characteristics of hydrometeors reflect ongoing microphysical processes in clouds and precipitation. The chapter describes basic microphysical processes and their influence on the evolution of hydrometeors and associated polarimetric radar variables. Some processes have unique polarimetric signatures or “fingerprints,” and examples of these are given here. The examined microphysical processes involve liquid cloud drops, raindrops, mixed-phase particles, and ice particles. Rain processes include condensation, evaporation, coalescence, breakup, and size sorting. Ice and mixed-phase processes include depositional growth, sublimation, riming, aggregation, freezing/refreezing, and melting.
Factors affecting the geographic variability of antibiotic-resistant healthcare-associated infections in the United States using the CDC Antibiotic Resistance Patient Safety Atlas

We utilized publicly available data from the Centers for Disease Control to explore possible causes of state-to-state variability in antibiotic-resistant healthcare-associated infections. Outpatient antibiotic prescribing rates of fluoroquinolones and cephalosporins explained some variability in extended-spectrum cephalosporin-resistant Escherichia coli after adjusting for differences in age and healthcare facility composition.
Functional Outcomes to Transanal Minimally Invasive Surgery (TAMIS) and Transanal Total Mesorectal Excision (taTME)

Anorectal physiology and bowel continence is a complex and dynamic coordination of the reservoir functional capacity of the rectum, dynamic interplay with pelvic floor musculature, and timely contraction and relaxation of the sphincter muscle complex. Surgical alteration of the rectum in the form of partial or complete resection significantly impacts the patient’s bowel habits. Transanal surgical partial or total resection is associated with postoperative functional impairment in bowel incontinence. This chapter reviews the impact of TAMIS and taTME on bowel functional outcomes.
Computing bounds for the general sum-connectivity index of some graph operations

Let \(G\) be a graph with vertex set \(V(G)\) and edge set \(E(G)\). Denote by \(d_{G}(u)\) the degree of a vertex \(u\in V(G)\). The general sum-connectivity index of \(G\) is defined as \(\chi_{\alpha}(G)=\sum_{u_{1}u_2\in E(G)}(d_{G}(u_1)+d_{G}(u_2))^{\alpha}\), where \(\alpha\) is a real number. In this paper, we compute the bounds for general sum-connectivity index of several graph operations. These operations include corona product, cartesian product, strong product, composition, join, disjunction and symmetric difference of graphs. We apply the obtained results to find the bounds for the general sum-connectivity index of some graphs of general interest.
Silicon Valley vs. Main Street: Regulatory Impact on Entrepreneurial Ventures

Over the last few decades, empirical evidence has suggested that business dynamism and entrepreneurial activity have been declining in the United States. Some scholars have linked this decline in entrepreneurial activity to the rise of regulatory burden on business entry and activity. However, during this same time period, there was a proliferation of technology startup activity. This presents a puzzle: while entrepreneurship in general seems to have been declining, a particular type of entrepreneurial venture seems to have grown. Drawing on original fieldwork interviews and an online survey of startups and venture capital investors, I provide a preliminary discussion of an unexplored explanation: the negative impact of regulation may have greater “weight” on “Main Street” entrepreneurs than on the “Silicon Valley” entrepreneurs.
Cigarette smoking behaviors and the importance of ethnicity and genetic ancestry

Cigarette smoking contributes to numerous diseases and is one of the leading causes of death in the United States. Smoking behaviors vary widely across race/ethnicity, but it is not clear why. Here, we examine the contribution of genetic ancestry to variation in two smoking-related traits in 43,485 individuals from four race/ethnicity groups (non-Hispanic white, Hispanic/Latino, East Asian, and African American) from a single U.S. healthcare plan. Smoking prevalence was the lowest among East Asians (22.7%) and the highest among non-Hispanic whites (38.5%). We observed significant associations between genetic ancestry and smoking-related traits. Within East Asians, we observed higher smoking prevalence with greater European (versus Asian) ancestry (P = 9.95 × 10-12). Within Hispanic/Latinos, higher cigarettes per day (CPD) was associated with greater European ancestry (P = 3.34 × 10-25). Within non-Hispanic whites, the lowest number of CPD was observed for individuals of southeastern European ancestry (P = 9.06 × 10-5). These associations remained after considering known smoking-associated loci, education, socioeconomic factors, and marital status. Our findings support the role of genetic ancestry and socioeconomic factors in cigarette smoking behaviors in non-Hispanic whites, Hispanic/Latinos, and East Asians.
A Theory of FinTech and Trade Finance

Problem Definition: Smart contract improves the supply chain efficiency by enabling the supplier's commitment to post-shipment financing that mitigates the bank's lending risk exposure and thereby reduces the financing cost. Invoice trading offers better liquidity and faster transaction speed, which allow the supplier to make the post-shipment financing decision upon liquidity shock in contrast to factoring market. This paper investigates how these two types of FinTech adoptions could facilitate the trade finance activities and create value for supply chain firms. Academic/Practical Relevance: As the emerging FinTechs could potentially reshape the trade financing landscape, understanding the impact of FinTech adoption and its interaction with trade finance activities is practically relevant and of great importance. Methodology: We develop a two-stage game-theoretic model and adopt supply chain finance theory to characterize firms' operations and financing strategies in the presence of various FinTech applications. Results: We find that the value of FinTech adoption depends critically on the trade financing structures, including both pre-shipment and post-shipment financing schemes. Under the baseline trade finance model (with purchase order financing and traditional factoring), smart contract leads to win-win outcome for the supplier and the retailer. When buyer direct financing is adopted for pre-shipment financing, smart contract might demotivate the retailer to offer buyer direct financing, which benefits the retailer but significantly hurts the supplier and therefore reduces the supply chain profit. When on-demand invoice trading is adopted for post-shipment financing, the supplier and retailer profit are increased due to its flexibility. However, it completely wipes out the value of smart contract since there exists no commitment issue. Lastly, though supply chain digitalization facilitated by FinTech helps lower the financing cost, it might either hurt the supplier or the retailer. Managerial Implications: Our findings provide guidelines for and insights into when smart contract and invoice trading should be adopted and their interactions with different trade finance schemes. In particular, such FinTechs do not always enhance the supply chain value.
H3K4 Di-Methylation Controls Smooth Muscle Cell Epigenetic Memory, Lineage Identity and Vascular Homeostasis

Epigenetic control of lineage-specific gene expression is essential for cell differentiation, acquisition of specialized functions, and tissue homeostasis. Here, we uncovered a unique epigenetic pathway critical for governing lineage identity and memory in cells presenting milieu-dependent phenotypic modulation in adult organisms. Using vascular smooth muscle cell (SMC), which are highly specialized contractile cells retaining extensive, yet reversible, plastic capacities in response to modifications in their environment, we found that the histone modification H3K4me2 is necessary for the maintenance of their lineage identity and functions by employing gene- and cell-specific chromatin editing. Selective removal of H3K4me2 on the SMC gene repertoire led to the marked loss of contractility and alteration of the SMC adaptive response during vascular remodeling. Rather than presenting intrinsic gene activation properties, H3K4me2 serves as a stable hub for the dynamic recruitment of the DNA methylcytosine dioxygenase Ten-Eleven Translocation 2 (TET2). The H3K4me2/TET2 complex controls the transcriptional activity of the SMC-specific gene repertoire, including contractile genes and miR-145, a key microRNA promoting SMC differentiation. These studies identified H3K4me2 imprinting as the central epigenetic mechanism controlling retention of lineage identity and cellular memory of SMC during adaptive processing requiring their transient dedifferentiation and phenotypic modulation and may have broad implications in the control of multiple plastic cell type behavior and functions in various pathophysiological processes.
Treatment of positive urine cultures in the neonatal intensive care unit: a guideline to reduce antibiotic utilization.

The pediatric definition of bacterial urinary tract infection (UTI) is >50,000 colony forming units (CFU) of a single organism on catheterized culture or 10,000–50,000 CFU with pyuria on urinalysis. The diagnosis of UTI in our NICU is clinician-dependent and not based on the accepted pediatric definition. A retrospective review of positive urine cultures between 2015 and 2017 was performed. A treatment guideline for positive urine cultures was adopted and PDSA methodology utilized for incremental improvements. For 909 pre-intervention neonates, 26 of 38 positive urine cultures were treated for UTI but only 23% (6/26) met the pediatric definition. For 644 post-guideline neonates, only 7 of 25 positive urine cultures were treated and 86% met guideline criteria with no increase in urosepsis. A guideline to treat positive urine cultures resulted in a decreased rate of UTI diagnosis and thus prevented unnecessary antibiotic exposure.
Delivery of Pharmacogenetic Testing with or without Medication Therapy Management in a Community Pharmacy Setting.

Objective The delivery of pharmacogenetic (PGx) testing has primarily been through clinical and hospital settings. We conducted a study to explore the feasibility of delivering PGx testing through community pharmacies, a less-studied setting. Methods We conducted a cluster randomized trial of community pharmacies in North Carolina through two approaches: the provision of PGx testing alone or PGx testing with medication therapy management (MTM). Results A total of 150 patient participants were enrolled at 17 pharmacies and reported high satisfaction with their testing experience. Participants in the PGx plus MTM arm were more likely to recall a higher number of results (p=0.04) and more likely to clearly understand their choices for prevention or early detection of side effects (p=0.01). A medication or dose change based on the PGx results was made for 8.7% of participants. Conclusion Limited differences were observed in the provision of PGx testing as a standalone test or combined with MTM. A limited number of treatment changes were made based on PGx test results. Patient acceptance of PGx testing offered through the community pharmacy was very high, but the addition of MTM did not impact patient-reported perceptions about PGx testing or medication adherence.
Carfilzomib, cyclophosphamide, and dexamethasone (KCd) for the treatment of triple-class relapsed/refractory multiple myeloma (RRMM).

Background Multiple myeloma (MM) is an incurable hematologic malignancy, and outcomes remain poor for patients with triple-class relapsed/refractory MM (RRMM). Descriptive analyses were performed on available data for patient characteristics, disease course, and outcomes of the KCd on triple-class RRMM patients at our institution. Patients and methods Twenty-three patients with triple-class RRMM treated with KCd between June 2017 and October 2020 were included in our analysis. The regimen KCd consisted of 28 days cycles of carfilzomib 20/36 mg/m2 IV on days 1, 2, 8, 9, 15, and 16, cyclophosphamide 300 mg/m2 IV weekly, and dexamethasone (20-40) mg orally weekly. Results Patients received a median of 6 (3-10) prior regimens. The median number of cycles administered was 4 (1-11) cycles. Overall response rate was 52%, 6 patients (26%) achieved very good partial response (VGPR), 6 patients (26%) achieved partial response (PR), and 5 patients (22%) achieved stable disease (SD). Progression-free survival (PFS) and Overall-survival (OS) were 4 and 11.9 months, respectively. There was no reported treatment-related mortality. The most common grade ≥3 adverse events were neutropenia (26%), thrombocytopenia (56.5%), and anemia (56.5%). Conclusions KCd showed clinically meaningful efficacy and manageable safety profile in patients with triple-class RRMM in real-world.
Meaning structures in the world polity: A semantic network analysis of human rights terminology in the world's peace agreements

Abstract We examine changes in the use of human rights language in peace agreement texts from 1990 to 2018. Existing research in world polity theory examines institutional change through the lens of increasing isomorphism, a lens that generally fails to appreciate qualitative transformations in the meaning of institutional concepts across time. As a corrective to this approach, we endorse a meaning-structure institutionalism that conceives institutional concepts in relational terms and use a method of textual analysis — semantic network analysis — to analyze and formally model the shifting meaning of human rights in peace agreement texts. We show that human rights language in peace agreements has undergone multiple qualitative shifts since its initial emergence in the mid-1980s. Specifically, the term human rights occupies a marginal position in peace agreement texts in the 1990s, is used in reference to and thus bridges multiple substantive themes in the 2000s, and, finally, inhabits a conceptual silo in the 2010s in the sense that it is associated with many concepts within but no concepts outside of a semantic community related to rights and democracy. We discuss implications for world polity theories of institutionalism that follow from our relational framework.
Does More Effective Director Monitoring Make Management Guidance More Credible

Evidence of the impact of governance on disclosure credibility is inconclusive. Based on a large, post-Regulation Fair Disclosure (Reg-FD) sample, we find that increased director monitoring – through increased director independence and director attention – is associated with more credible management guidance, as evidenced by stronger analyst reactions to the news in management guidance. We document additional cross-sectional differences in the monitoring/credibility link, consistent with monitoring being particularly impactful when the role of external verification is largest (good news forecasts, low analyst following). We are able to identify causal effects through exogenous shocks to monitoring associated with (1) director deaths, (2) mandated independence required by Sarbanes-Oxley (SOX), and (3) changes in director attention due to M&A activities that eliminate board positions at other firms. This finding does not appear to be due to a link between effective monitoring and more accurate guidance, as the stronger analyst reactions occur only when guidance is less accurate. Overall, our findings provide strong support for director monitoring influencing the perceived credibility of management forecasts, especially in settings where external validation is needed.
Smoothing of PV Output Power in Grid-Tied Energy Storage System with Model Predictive Control and Battery Lifetime Consideration

This paper presents a control strategy for intermittent photovoltaic (PV) system when coupled with battery energy storage (BES) connected to the grid and the load. We use model predictive control (MPC) framework to allow the BES to adapt dynamically and provide control actions according to PV output fluctuation while satisfying several constraints including meeting the grid ramp rate requirement, and addressing the maximum battery charge/discharge power constraint and state of charge (SoC) limitation. The system is represented as a discrete time state space model and convex objectives are minimized subjected to system constraints providing optimal control input. Moving average (MA) filter is used to generate the reference power and window size is selected by considering the maximum grid ramp rate and battery lifetime. Time series forecasting model has been developed based on PV data to establish novel integrated MPC method for better energy management system incorporating battery lifetime considerations. The simulation performed in Matlab/Simulink demonstrates that the proposed control method can track the reference power while maintaining the functional requirement of the BES unit and the grid efficiently as well as preserving battery lifetime significantly.
Operators for Angular Momentum and Spin

When the eigenstates for a mode, or modes, of motion in a given system form a simple sequence or ladder, these states may be interconverted by applying an operator that moves the system up or down the ladder. In Section 5.7, such operators were constructed for the states of a harmonic oscillator; in Section 5.11, step-up and step-down operators were formulated for the radial motion of a particle in a Coulombic field.
Linear Plasmids in Bacteria: Common Origins, Uncommon Ends

This chapter reviews the structure and replication of bacterial linear plasmids. Examples are given of the varying structures of the termini (telomeres) of linear plasmids from representative bacteria, and proposed mechanisms for telomere replication and resolution are described. Although the focus is on linear plasmids, most of what is described in the chapter also applies to linear bacterial chromosomes. The first bacterial linear plasmid was described in 1979 from the antibiotic-producing soil microbe Streptomyces rochei. A few species with linear plasmids or chromosomes have also been found in the alpha, beta, and gamma divisions of the genus Proteobacteria. In bacteria with polyploid stages, such as the mycelium of Streptomyces, linear DNA may segregate with fewer mishaps than circular DNA. Alternatively, one could argue that conversion of a circular replicon to a linear form was an inadvertent but neutral event. Linear plasmids have also been identified in the actinomycetes Rhodococcus fascians, R. erythropolis, Clavibacter michiganensis, Nocardia opaca, Planobispora rosea, and the proteobacteria Thiobacillus versutus and Xanthobacter autotrophics. Linear plasmids generally retain the same features and mechanisms for replication initiation as their circular counterparts. Recent experiments demonstrate that replication initiates from an internal origin and continues around the hairpin telomeres, resulting in a circular dimer. The segregation systems of all linear plasmids characterized to date, regardless of telomere structure, appear to be analogous to those of circular plasmids.
Immediate Hypersensitivity: A Brief History

Publisher Summary This chapter focuses on a brief history of immediate hypersensitivity. After the discovery of transmission of anaphylactic sensitivity, it became possible to study human hypersensitivity experimentally with the Prausnitz–Kustner reaction. The importance of histamine liberation in human allergic reactions led Bovet to the discovery of synthetic antihistamines, for which Bovet was later awarded the Nobel prize. Hypersensitivity has been known since antiquity. One of the most sensational stories is that of Girolamo Gardano, the great renaissance mathematician who in 1552 cured the asthma of John Hamilton, the Archbishop of St Andrews, Scotland, by taking away his swan-feathered pillows. In 1942, Merrill Chase made the fundamental discovery that delayed (tuberculin type) hypersensitivity reactions could be transferred by living lymphocytes and that immediate (anaphylactic) type reactions are transferred by antibody. Using the action of histamine on the permeability of small veins, passive cutaneous anaphylaxis (PCA) was developed.
Finding Space for Criminal Prosecutions Post‐Conflict

Post-conflict criminal prosecutions for the worst of crimes can play a meaningful role in achieving transitional justice. This once-common view has recently been the subject of widespread criticism that is rooted in the belief that criminal prosecutions undermine reconciliation. This has lead some scholars to argue that we must either abandon criminal prosecutions post-conflict or that we ought to use them for more general transitional justice aims, like restorative justice. This article argues against abandoning criminal prosecutions post conflict and against subsuming criminal justice aims under restorative or reconciliatory aims. When post-conflict criminal prosecutions are properly structured and practiced they can bolster respect for the international, regional and domestic rule of law and in that way limit conflict in a number of important ways.
107 Modifications modulate anticodon loop dynamics and codon recognition in E. coli tRNAArg1,2

In Escherichia coli, three of six arginine codons (CGU, CGC and CGA) are decoded by only two tRNAArg isoacceptors. The anticodon-stem loop (ASL) domains of tRNAArg1 and tRNAArg2 differ only at posi...
Protection by histamine receptor antagonists and prostaglandin against gastric mucosal barrier disruption in the rat

Abstract This study was undertaken to determine if the cytoprotective effect of prostaglandin and the H2 histamine receptor antagonist cimetidine involves protection against disruption of the gastric mucosal barrier. Groups of anesthetized, vagotomized rats received one of the following parenterally: saline (control), mepyramine—an H1 histamine receptor antagonist, cimetidine, cimetidine and mepyramine, or 16,16 dimethyl prostaglandin E2. Parameters of barrier disruption were then determined beforeand after exposure of the gastric mucosa to 40mM acetylsalicylic acid. At the end of the study, gastric lesions were scored according to size and number. Lesion score and fall in potential difference were significantly lower in rats receiving cimetidine, cimetidine and mepyramine, and prostaglandin. Other parameters of barrier disruption—H+ back diffusion, Na+ and K+ influx, and protein outpouring—exhibited the same pattern and correlated with change in potential difference. We conclude that both prostaglandin and cimetidine, but not mepyramine, protect against barrier disruption by topical aspirin, and this may be a factor in the mechanism of their cytoprotective action.
EXPERIMENTAL VERIFICATION OF TIME-DEPENDENT ACCUMULATION PREDICTIONS IN CONGESTED TRAFFIC

With experimental traffic data from a 4-mi (6.44-km) long congested road, it is shown that traffic delays and vehicle accumulations between any two generic observers located inside the road section can be predicted quite accurately from the traffic counts measured at the extremes of the section. Predictions can be made with a streamlined version of the kinematic wave theory that does not rely on ambiguous traffic stream characteristics such as density. The predictions were found not to require recalibration on the day of the experiment and to work well despite what appeared to be location-specific driver behavior.
Biochemical changes in copper deficiency.

Article de synthese traitant des aspects fonctionnels biochimiques du cuivre chez l'animal et des parametres biochimiques d'une deficience en cuivre. Homeostasie. Cuproenzymes. Cuproproteines. Carence en cuivre: changements biochimiques et pathologiques. Specificite de sensibilite des organes et des cuproenzymes au deficit en Cu
The Fate of Nephrons in Congenital Obstructive Nephropathy: Adult Recovery is Limited by Nephron Number Despite Early Release of Obstruction

Purpose: Urinary tract obstruction and reduced nephron number often occur together as a result of maldevelopment of the kidneys and the urinary tract. We determined the role of nephron number on adaptation of the remaining nephrons of mice subjected to neonatal partial unilateral ureteral obstruction followed through adulthood.Materials and Methods: Wild-type and Os/+ mice (the latter with 50% fewer nephrons) underwent sham operation or partial unilateral ureteral obstruction in the first 2 days of life. Additional mice underwent release of unilateral ureteral obstruction at 7 days. All kidneys were harvested at 3 weeks (weaning) or 6 weeks (adulthood). Glomerular number and area, glomerulotubular junction integrity, proximal tubular volume fraction and interstitial fibrosis were measured by histomorphometry.Results: In the obstructed kidney unilateral ureteral obstruction caused additional nephron loss in Os/+ but not in wild-type mice. Glomerular growth from 3 to 6 weeks was impaired by ipsilateral obst...
Failure behavior of 304L stainless steel in torsion

The workability of 304L austenitic stainless steel has been investigated using torsion testing at temperatures from 20 °C to 1200 °C and strain rates of 0.01 and 10.0s -1 For the lower strain rate, temperature changes due to deformation heating were minimal, and failure was found to be fracture controlled at all temperatures. As for many other metals, the 304L exhibited a ductility minimum at warm-working temperatures. For the higher strain rate, failure was controlled by flow-localization processes at 20 °C and 200 °C. At these temperatures, flow softening resulting from deformation heating was deduced to be the principal cause of flow localization. A model to predict the strain at the onset of localization was developed and applied successfully to the 304L results. For high strain-rate torsion tests at 400 °C and above, failure was fracture controlled as in the low strain-rate tests, and the ductilities were shown to be correlated to those at the lower strain rate through the Zener-Hollomon parameter by employing an activation energy derived from flow-stress data.
Distribution of cerebral microembolism in the anterior and middle cerebral arteries.

BACKGROUND AND PURPOSE Cerebral infarcts occur more frequently along the middle (MCA) than the anterior cerebral artery (ACA) territory. The reason(s) for this difference remains speculative. The objective of this study was to investigate the distribution of cerebral microemboli as detected by transcranial Doppler ultrasound (TCD) along the MCA and ACA territories. METHODS Records of consecutive patients examined for the presence of cerebral microembolism during a 32-month period at the Neurovascular Laboratory were reviewed. Of the original 375 TCD studies in 268 patients, 28 studies in 24 patients demonstrated microembolic signals (MES) and monitored the MCA and ACA on the same side. TCD studies were performed on TC-2000 or TC-2020 instruments. MES positive studies were saved and off-line reviewed. MES satisfied previously established criteria. RESULTS MES were more frequent in the MCA than the ACA in 85.7% (24/28) of studies (P < 0.01). Of the total number of MES (n = 979), 29.6% (n = 290) were detected in the ACA and 70.4% (n=689) in the MCA (P<0.01). The mean (+/- SD) intensity of MCA MES of 12.2 (+/- 2.4) dB was significantly lower than that of ACA MES of 14.8 (+/-3.2) dB (P=0.05). The mean (+/-SD) duration of MCA MES of 38.1 (+/- 45.3) ms was longer than that of ACA MES of 30.7 (+/-34.0) ms (P=0.05). CONCLUSIONS Cerebral microembolism occurs more frequently in the MCA than the ACA, which may explain the uneven distribution of cerebral infarcts along these arterial territories. Furthermore, there are significant differences in the characteristics of ACA and MCA MES.
Microgrids: Technical and security recommendations for future implementations

Microgrids are modern, localized versions of the centralized utility grid. They have been gaining popularity due to the increased power demand and the development of various renewable resources. In this paper, we present technical and security recommendations for modern microgrid implementations to ensure interoperability, reliability, and security.
Zona incerta lesions impair osmotic but not hypovolemic thirst.

Abstract Male albino rats with bilateral lesions of the anterior zona incerta are hypodipsic when dry food is available and show little or no regulatory drinking when food deprived. They do, however, drink normal quantities of water in response to subcutaneous injections of polyethylene glycol that produce extracellular hypovolemia. In contrast, they show a markedly reduced response to intracellular dehydration produced by intraperitoneal injections of hypertonic saline. The osmotic thirst deficit is not due to an increased latency of response to the injections.