cssi/SciSciGPT-SciSciNet huggingface dataset:
The Use of Therapeutic Jurisprudence in Law School Clinical Education

William and Mary Law School, a public institution of the Commonwealth of Virginia, its roots deeply entrenched in the archives of legal learning, might not be a place you would expect to see an externship with the heading Therapeutic Courts Practice. However, the law school as part of its mission to produce graduates who are not simply powerful advocates and wise counselors, but also honorable and concerned human beings and good citizens has taken up the cause of Therapeutic Jurisprudence and problem-solving courts. In Part I of my paper, I discuss the basic tenets of Therapeutic Jurisprudence and how it integrates quite nicely with clinical education. Part II is reserved for a discussion of problem-solving courts, sometimes called therapeutic courts. Further, I describe the close relationship that exists between Therapeutic Jurisprudence and problem-solving courts, and how the two complement each other. Part III introduces the William & Mary Law School model of a therapeutic courts externship and how students are introduced to the principles of Therapeutic Jurisprudence. It is here that the nuts and bolts of the course are described in some detail. This part also serves as an opportunity to discuss Virginia's Drug Treatment Court Program, including the use of juvenile, family and adult drug treatment courts of the Commonwealth in placing externs. It is here that I also pay particular attention to the reactions of students to the therapeutic externship experience. My hope with the student reports is to convey a very consistent and important message heard from my students: Therapeutic Jurisprudence has a real place in the law school curriculum, and is especially useful in the clinical and legal skills area. I have devoted the major theme of this paper to the creation and implementation of an externship devoted solely to the practice of therapeutic courts. It is my hope that others will consider doing the same. In its relatively short life span it has proven exciting, invigorating and stimulating to students. In evaluating any new program or course, student reaction is one of the most important considerations. As good vibes continue to flow from the experience, good will for Therapeutic Jurisprudence continues to build with law school administration and faculty, many of whom were skeptics in the first place. At William & Mary Law School, I'm grateful that when opportunity came knocking, someone was listening. To some, opportunity is seen as a risk or chance. To others, it is viewed similarly but with an added sense of advancement for the common good. The opportunities that are present with a program in Therapeutic Jurisprudence and an externship in Therapeutic Courts Practice are endless. As we all labor in the vineyards to enrich the lives of our student's legal education, let us not be afraid to do what we teach our students to do, think and discover the possibilities and then in turn, seize on the new opportunities of the day.
Atrial Myxoma Presenting as Myocardial Infarction Diagnosed by Echocardiography, Managed Endoscopically with Robot-Assisted Surgery

Atrial myxomatous embolization into the coronary arteries is a rare event. Management of large myxomas is usually via surgical resection involving a median sternotomy. Echocardiography is not a routine part of non-ST-elevation myocardial infarction (NSTEMI) management. Here, we present the case of a 70-year-old Caucasian man with a history of hypertension and hyperlipidemia who presented to the emergency department with an NSTEMI. Transthoracic echocardiogram and transesophageal echocardiogram revealed a large and highly mobile atrial mass, traversing through the mitral valve orifice during diastole. Coronary angiography revealed a focal 60% lesion in the right coronary artery and no other significant obstructive coronary artery disease, suggesting that the cause of his presentation was tumor embolization into the coronary circulation. The patient underwent robot-assisted endoscopic resection of his atrial mass and was discharged in stable condition on postoperative day 2. Pathology revealed atrial myxoma. To our knowledge, this is the first reported case of an atrial myxoma presenting with an NSTEMI and managed with a robot-assisted endoscopic approach. This case also highlights the importance of routine early echocardiography in patients presenting with NSTEMI.
The Reaction of HCCO + O2: Experimental Evidence of Prompt CO2 by Time-Resolved Fourier Transform Spectroscopy

The products CO and CO 2 are observed experimentally for the first time in the HCCO + O 2 reaction. Both product molecules have identical appearance times and are formed simultaneously rather than sequentially. Both CO and CO 2 are produced with significant internal excitation. The product channel producing H + CO + CO 2 accounts for at least 90% of the reaction products at 298 K. The results explain the observation of "prompt" CO 2 in acetylene oxidation chemistry.
The Construction of Core-functional Zone: The Option of New Model For Rebuilding Western Ecological Environment

The traditional western region development strategy, primary focusing on the economic incremental purpose, has driven the already fragile western ecological environment status much worsened as it dramatically fosters the local economic booming simultaneously. Although the specialists have conducted the extensive study on these particular issues, the effective measurement has not been found to mitigate the controversy between the economic development and ecological protection. Therefore, the traditional concept of economic development and ecological environment protection shall be reexamined surrounding the construction of Core-functional Zone, to explore the new theories, as well as new ideas, and new model which are feasible to western ecological environment construction.
Sorafenib Effectiveness in Advanced Hepatocellular Carcinoma

Background Phase III trials show sorafenib improves survival in advanced hepatocellular carcinoma (HCC). Because of narrow trial eligibility, results may not be generalizable to a broader HCC population. We sought to evaluate the effectiveness of initial sorafenib versus no treatment among Medicare beneficiaries with advanced HCC. Materials and methods Patients with advanced HCC diagnosed from 2008 to 2011 were identified from the Surveillance, Epidemiology, and End Results-Medicare database. Eligible patients received initial sorafenib or no therapy and were covered by Medicare parts A, B, and D. Sorafenib use and outcomes were described in this population. Using a propensity score (PS)-matched sample, we compared the effectiveness of sorafenib versus no treatment by Cox proportional hazards and binomial regression, using a landmark requiring all patients to survive ≥60 days after diagnosis. Results Of 1,532 patients, 27% received initial sorafenib. Median duration of sorafenib use was 60 days (interquartile range [IQR], 30-107 days), and median survival from first prescription was 3 months (IQR, 1-8 months). In the PS-matched cohort, median survival was 3 months from the 60-day landmark in sorafenib-treated (n = 223) and 2 months in untreated (n = 223) patients (adjusted hazard ratio, 0.95 [95% confidence interval (CI), 0.78-1.16]). Sorafenib was associated with a nonsignificant reduction in mortality at 3 months (44% versus 51%; adjusted risk ratio, 0.88 [95% CI, 0.72-1.07]), but no reduction thereafter. Conclusion Survival after sorafenib initiation in newly diagnosed Medicare beneficiaries with HCC is exceptionally short, suggesting trial results are not generalizable to all HCC patients. The downsides of sorafenib use-high drug-related symptom burden and high drug cost-must be considered in light of this minimal benefit. Implications for practice The findings of a median survival of only 3 months in Medicare beneficiaries with HCC prescribed sorafenib as first-line therapy highlight the questionable value of sorafenib in this population. Patients should be cautioned that outside of the narrow confines of randomized trials, their life expectancy may be very short, and any benefit of sorafenib is likely to be quite small. Given that sorafenib causes considerable adverse effects and offers no symptom palliation, supportive care should be discussed as a reasonable alternative to sorafenib, particularly for patients who have a poor performance status or advanced cirrhosis.
Mumps and rubella.

Abstract This chapter reviews the major neurologic manifestations associated with mumps and rubella infection. Both mumps and rubella demonstrate neurotropism and are associated with multiple central nervous system infectious as well as parainfectious syndromes. While infections are waning globally with the successful implementation of large-scale vaccination programs, these viruses remain important pathogens given inconsistent vaccination in some areas of the developing world, particularly so in politically unstable regions. The facility of international travel for unimmunized individuals continues to contribute to neurologic complications across the globe. Important elements of neuropathogenesis, disease epidemiology and natural history, and associated clinical syndromes of mumps and rubella infection are highlighted in this chapter.
Introduction and Overview of the Third Edition

In recent times, authors of macroeconomics texts have faced a series of daunting challenges. The primary challenge lies in the very nature of the subject.
Orbits of massive satellite galaxies - I. A close look at the Large Magellanic Cloud and a new orbital history for M33

National Science Foundation [DGE-1143953, 1228509]; HST programme [AR-12632]; NASA through the Space Telescope Science Institute [AR-12632]; NASA [NAS 5-26555]; FAS Science Division Research Computing Group at Harvard University
Routes of transmission of Salmonella and Campylobacter in breeder turkeys

Abstract Salmonella and Campylobacter are frequent colonizers of the intestinal tracts of poultry and have often been associated with human foodborne illness. The entry, transmission, and prevalence of both pathogens have been extensively studied in chickens but little information is available for turkeys. This project monitored turkey breeder hens and toms from d of hatch to 65 wk of age with the objective of determining routes of transmission for Salmonella and Campylobacter throughout the turkey production cycle. Breeder poults were separated by sex and then into 2 groups (control and inoculated) for each sex. The inoculated group was orally gavaged with marker strains of both Salmonella and Campylobacter. The inoculated groups (toms and hens) were placed on the opposite side of a growout house from the uninoculated groups. Fecal samples, intestinal samples and organs, feed, drinkers, and potential vectors such as insects and mice, were analyzed at different times until 65 wk. Monitoring showed that Campylobacter spread rapidly and cross-contaminated turkeys throughout the growout house. For both Salmonella and Campylobacter, naturally occurring strains that were first isolated in control groups at wk 3 and 4, respectively, outcompeted marker strains several wk post inoculation and persisted in the flock. The most common naturally occurring strains were C. jejuni (tetracycline resistant), C. coli (kanamycin resistant), and S. Agona. Campylobacter and Salmonella also were isolated from flies and from a mouse, confirming the importance of proper pest control and biosecurity to reduce the spread of the bacteria.
UV Spectra of Tris(2,2′-bipyridine)–M(II) Complex Ions in Vacuo (M = Mn, Fe, Co, Ni, Cu, Zn)

We present electronic spectra in the π–π* region of a series of tris(bpy)–M(II) complex ions (bpy = 2,2′-bipyridine; M = Mn, Fe, Co, Ni, Cu, Zn) in vacuo for the first time. By applying photodissociation spectroscopy to cryogenically cooled and mass selected [MII(bpy)3]2+ ions, we obtain the intrinsic spectra of these ions at low temperature without perturbation by solvent interaction or crystal lattice shifts. This allows spectroscopic analysis of these complex ions in greater detail than possible in the condensed phase. We interpret our experimental data by comparison with time-dependent density functional theory.
Bacterial Energy Sensor Aer Modulates the Activity of the Chemotaxis Kinase CheA Based on the Redox State of the Flavin Cofactor.

Abstract Flagellated bacteria modulate their swimming behavior in response to environmental cues through the CheA/CheY signaling pathway. In addition to responding to external chemicals, bacteria also monitor internal conditions that reflect the availability of oxygen, light, and reducing equivalents, in a process termed "energy taxis." In Escherichia coli, the transmembrane receptor Aer is the primary energy sensor for motility. Genetic and physiological data suggest that Aer monitors the electron transport chain through the redox state of its FAD cofactor. However, direct biochemical data correlating FAD redox chemistry with CheA kinase activity have been lacking. Here, we test this hypothesis via functional reconstitution of Aer into nanodiscs. As purified, Aer contains fully oxidized FAD, which can be chemically reduced to the anionic semiquinone (ASQ). Oxidized Aer activates CheA, whereas ASQ Aer reversibly inhibits CheA. Under these conditions, Aer cannot be further reduced to the hydroquinone, in contrast to the proposed Aer signaling model. Pulse ESR spectroscopy of the ASQ corroborates a potential mechanism for signaling in that the resulting distance between the two flavin-binding PAS (Per-Arnt-Sim) domains implies that they tightly sandwich the signal-transducing HAMP domain in the kinase-off state. Aer appears to follow oligomerization patterns observed for related chemoreceptors, as higher loading of Aer dimers into nanodiscs increases kinase activity. These results provide a new methodological platform to study Aer function along with new mechanistic details into its signal transduction process.
Impact of Socioeconomic Status on Patients Supported With a Left Ventricular Assist Device: An Analysis of the UNOS Database (United Network for Organ Sharing).

Background— Low socioeconomic status (SES) is a known risk factor for heart failure, mortality among those with heart failure, and poor post heart transplant (HT) outcomes. This study sought to determine whether SES is associated with decreased waitlist survival while on left ventricular assist device (LVADs) support and after HT. Methods and Results— A total of 3361 adult patients bridged to primary HT with an LVAD between May 2004 and April 2014 were identified in the UNOS database (United Network for Organ Sharing). SES was measured using the Agency for Healthcare Research and Quality SES index using data from the 2014 American Community Survey. In the study cohort, SES did not have an association with the combined end point of death or delisting on LVAD support ( P =0.30). In a cause-specific unadjusted model, those in the top (hazard ratio, 1.55; 95% confidence interval, 1.14–2.11; P =0.005) and second greatest SES quartile (hazard ratio 1.50; 95% confidence interval, 1.10–2.04; P =0.01) had an increased risk of death on device support compared with the lowest SES quartile. Adjusting for clinical risk factors mitigated the increased risk. There was no association between SES and complications. Post-HT survival, both crude and adjusted, was decreased for patients in the lowest quartile of SES index compared with all other SES quartiles. Conclusions— Freedom from waitlist death or delisting was not affected by SES. Patients with a higher SES had an increased unadjusted risk of waitlist mortality during LVAD support, which was mitigated by adjusting for increased comorbid conditions. Low SES was associated with worse post-HT outcomes. Further study is needed to confirm and understand a differential effect of SES on post-transplant outcomes that was not seen during LVAD support before HT.
STRD MARTINI: Simulating Quasi-2D Hydrodynamics with Chemically Detailed Lipid Models

Hydrodynamic interactions are an important component of lipid membrane dynamics. A proper molecular dynamics simulation of lateral diffusion in a membrane requires coupling to hydrodynamic flows in the surrounding solvent. In the low Reynolds number limit, the interactions mediated by these flows are long-ranged. Camley, et al recently generalized the Saffman-Delbruck result to periodic boundary conditions, and showed that hydrodynamic interactions introduce significant error into lateral diffusion of lipids and proteins in typical molecular dynamics simulations. The system sizes required to overcome the finite size effect are computationally prohibitive when using explicit solvent models in both all-atom and coarse-grained simulation. Implicit solvent models offer a potential solution, but entirely neglect hydrodynamic momentum transport. To remedy this, we have supplemented the Dry MARTINI implicit solvent model with an efficient mesoscopic particle-based hydrodynamic model called Stochastic Rotation Dynamics (SRD). Our implementation allows for fine control over fluid properties of the solvent, such as viscosity and Reynolds number, and includes a thermostat for the solvent that produces canonical energy fluctuations without interfering with the mesoscopic hydrodynamic flows. The approach, dubbed “STRD Martini”, has been implemented in an in-house version of Gromacs v 5.1.
Perception in Romantic Relationships: a Latent Profile Analysis of Trait Mindfulness in Relation to Attachment and Attributions

To advance understanding of the role of trait mindfulness in attributions for romantic partner transgressions, we examined the direct and indirect associations among attachment, trait mindfulness, and attributions in a sample of 542 young adults in romantic relationships. A latent profile analysis was used to identify four classes of trait mindfulness (i.e., High Mindfulness, Nonjudgmentally Aware, Low Mindfulness, Judgmentally Observing), and a subsequent structural equation model revealed several significant associations among attachment, the classes of trait mindfulness, and benign attributions for partner transgressions. For example, the High Mindfulness class and the Nonjudgmentally Aware class were positively associated with benign attributions. Furthermore, two significant indirect effects emerged. First, heightened attachment anxiety was associated with a decreased probability of being in the Nonjudgmentally Aware class, which was linked to a decrease in benign attributions. Second, avoidant attachment was associated with a decreased probability of membership in the High Mindfulness class, which was linked to a decrease in benign attributions. Areas for future research based on the findings of this study are discussed.
The effects of attribute non-attendance, simple validation questions, and their interactions on willingness to pay estimates for meat choice experiments

During an online survey, respondents were randomly assigned to a choice experiment for either pork chops or chicken breasts and were then explicitly asked which attributes they did not consider whi...
Mother's Lived Experience During Repair of Long-Gap Esophageal Atresia: A Phenomenological Inquiry.

BACKGROUND Infants born with long-gap esophageal atresia (LGEA) pose unique physiologic risks in the newborn period. Anatomic and physiologic anomalies require an extended hospitalization with procedural analgesia and sedation that impact the mother's experience of birth, maternal response, and nurturing of her infant. PURPOSE The aim of this study was to understand the meaning of experiences that mothers of infants born with LGEA encounter in the neonatal intensive care unit while their infant undergoes esophageal repair. METHODS A hermeneutical phenomenological design was used to guide this inquiry. Three mothers were interviewed on 3 separate occasions. The conversations were audio-recorded and transcribed verbatim. The findings were analyzed using fundamental existential lifeworld themes. RESULTS The essence that conceptualized the study was "making connections: day-by-day." Themes that emerged are (a) the many phases; (b) the long and winding road; (c) a new me, my purpose; and (d) our new community. IMPLICATIONS FOR PRACTICE Nurses' knowledge and understanding of maternal experiences of having an infant with LGEA will enable for increased physical closeness, optimizing time spent together to learn their infant's unique personality. Creating partnerships with mothers can enhance our understanding of their perspectives, concerns, needs, and guide interventions. IMPLICATIONS FOR RESEARCH Further exploration of family dynamics including fathers, siblings, and contextual factors may illuminate interventions to enhance relationships and communication that may influence developmental outcomes for families of infants with LGEA.
Acute Febrile Illness and Complications Due to Murine Typhus, Texas, USA1,2

Murine typhus occurs relatively commonly in southern Texas, as well as in California. We reviewed records of 90 adults and children in whom murine typhus was diagnosed during a 3-year period in 2 hospitals in southern Texas, USA. Most patients lacked notable comorbidities; all were immunocompetent. Initial signs and symptoms included fever (99%), malaise (82%), headache (77%), fatigue (70%), myalgias (68%), and rash (39%). Complications, often severe, in 28% of patients included bronchiolitis, pneumonia, meningitis, septic shock, cholecystitis, pancreatitis, myositis, and rhabdomyolysis; the last 3 are previously unreported in murine typhus. Low serum albumin and elevated procalcitonin, consistent with bacterial sepsis, were observed in >70% of cases. Rash was more common in children; thrombocytopenia, hyponatremia, elevated hepatic transaminases, and complications were more frequent in adults. Murine typhus should be considered as a diagnostic possibility in cases of acute febrile illness in southern and even in more northern US states.
Selecting the State or Choosing the Chief? The Political Determinants of Smallholder Land Titling

Summary This article examines the effect of customary institutions on smallholder land titling in Sub-Saharan Africa. It argues that the individual’s status within the customary institution conditions his or her demand for land titles. Individuals with greater customary privilege gain advantages from maintaining customary property rights, including stronger tenure security. For households with lower privilege within the customary institution, the benefits of adopting state land titles are higher. Analysis of an original survey of smallholder farmers in Senegal and an existing survey in Zambia demonstrates that households with greater customary privilege are less likely to adopt state land titles, independent of ethnicity, wealth, and land values. I find additional support for the argument in measures of increased tenure security for those with greater customary privilege. Qualitative interviews with customary authorities and smallholder farmers help establish the mechanism. These findings update the dominant wisdom that land values and material transaction costs drive smallholder land titling, demonstrating the important effect of status within the customary institution on demand for land titles. By examining the political underpinnings of customary property rights, this article contributes to our understandings of which farmers benefit most from land titling. This has implications for the improved design of land governance programs.
Increased Calcium Buffering in Basal Forebrain Neurons During Aging

Increased calcium buffering in basal forebrain neurons during aging. J. Neurophysiol. 80: 350-364, 1998. Alterations of neuronal calcium (Ca2+) homeostasis are thought to underlie many age-related changes in the nervous system. Basal forebrain neurons are susceptible to changes associated with aging and to related dysfunctions such as Alzheimer's disease. It recently was shown that neurons from the medial septum and nucleus of the diagonal band (MS/nDB) of aged (24-27 mo) F344 rats have an increased current influx through voltage-gated Ca2+ channels (VGCCs) relative to those of young (1-4. 5 mo) rats. Possible age-related changes in Ca2+ buffering in these neurons have been investigated using conventional whole cell and perforated-patch voltage clamp combined with fura-2 microfluorimetric techniques. Basal intracellular Ca2+ concentrations ([Ca2+]i), Ca2+ influx, Ca2+ transients (Delta[Ca2+]i), and time course of Delta[Ca2+]i were quantitated, and rapid Ca2+ buffering values were calculated in MS/nDB neurons from young and aged rats. The involvement of the smooth endoplasmic reticulum (SER) was examined with the SER Ca2+ uptake blocker, thapsigargin. An age-related increase in rapid Ca2+ buffering and Delta[Ca2+]i time course was observed, although basal [Ca2+]i was unchanged with age. The SER and endogenous diffusible buffering mechanisms were found to have roles in Ca2+ buffering, but they did not mediate the age-related changes. These findings suggest a model in which some aging central neurons could compensate for increased Ca2+ influx with greater Ca2+ buffering.
Social interactions and androgen levels in birds. I. Female characteristics associated with increased plasma androgen levels in the male ring dove (Streptopelia risoria).

Abstract Male ring doves exposed to female conspecifics exhibit a variety of courtship behaviors and show large and relatively long-lasting elevations in circulating androgens. This series of experiments examined whether (1) a female's gonadal condition and (2) contact or auditory cues from the mating situation influence these changes in male androgen levels and courtship behavior. Pairs of doves were placed in breeding cages, their behavior observed for the first 15 min of exposure, and blood obtained from the males 24 hr after pairing. Androgen levels were determined by an RIA. Males exposed to ovariectomized females had lower androgen levels than males exposed to intact females (2.3 ± 0.3 vs 4.0 ± 0.8 ng/ml, X ± SEM ), indicating that a female's gonadal condition influences a male's endocrine response to her. Deaf males exposed to intact females had lower androgen levels (1.4 ± 0.6 ng/ml) than normal males exposed to females (4.0 ± 0.8 ng/ml), indicating that auditory cues from the mating situation influence female-induced elevations in male plasma androgens. Males exposed to females through glass partitions had androgen levels (2.7 ± 0.6 ng/ml) similar to males given free access to females and higher androgen levels than males in isolation, indicating that contact cues from the mating situation do not necessarily influence female-induced elevations in male plasma androgens. The results also indicate that (1) contact between a pair of doves during early courtship facilitates male aggressive courtship displays and reduces male nest-oriented behavior, and (2) auditory cues from the mating situation facilitates male courtship behavior.
Risk of Incident Liver Disease in Patients with Psoriasis, Psoriatic Arthritis, and Rheumatoid Arthritis: A Population-Based Study

Relatively little is known about the risk for incident liver disease in psoriasis (PsO), psoriatic arthritis (PsA), and rheumatoid arthritis (RA). We performed a cohort study among patients with PsO, PsA, or RA and matched controls in The Health Improvement Network from 1994 to 2014. Outcomes of interest were any liver disease, nonalcoholic fatty liver disease, and cirrhosis (any etiology). Among patients with PsO (N = 197,130), PsA (N = 12,308), RA (N = 54,251), and matched controls (N = 1,279,754), the adjusted hazard ratios for any liver disease were elevated among patients with PsO (without systemic therapy [ST] 1.37; with ST 1.97), PsA (without ST 1.38; with ST 1.67), and RA without an ST (1.49) but not elevated in patients with RA prescribed an ST (0.96). Incident nonalcoholic fatty liver disease was highest in patients with PsO prescribed an ST (2.23) and PsA with an ST (2.11). The risk of cirrhosis was highest among patients with PsO with an ST (2.62) and PsA without an ST (3.15). Additionally, the prevalence of liver disease and cirrhosis increased in a stepwise fashion with increasing body surface area affected by PsO (P for trend
Trading frictions in Indian village economies

Abstract This paper presents evidence of trading frictions in rural Indian villages. I first introduced a new seed variety to a random subset of farmers in 82 villages. I then allowed the new variety to diffuse through farmer-to-farmer trading in a random half of villages. This mode of exchange is compared with demand that was approximated by selling the same seeds directly to farmers in the other half of villages. I find that direct trading between farmers leads to substantial under-adoption when compared to door-to-door sales — suggesting that trading frictions exist and represent a barrier to technological diffusion. Caste identity explains some, but not all, of this puzzle. Specifically, farmers sharing the same surname or belonging to the same subcaste as the original seed recipients adopt at higher rates when farmers trade amongst themselves. Overall, the trading frictions in farmer-to-farmer exchange are severe enough to make door-to-door sales cost effective.
Farnesoid X Receptor Agonists Obeticholic Acid and Chenodeoxycholic Acid Increase Bile Acid Efflux in Sandwich-Cultured Human Hepatocytes: Functional Evidence and Mechanisms.

The farnesoid X receptor (FXR) is a nuclear receptor that regulates genes involved in bile acid homeostasis. FXR agonists, obeticholic acid (OCA) and chenodeoxycholic acid (CDCA), increase mRNA expression of efflux transporters in sandwich-cultured human hepatocytes (SCHH). This study evaluated the effects of OCA and CDCA treatment on the uptake, basolateral efflux, and biliary excretion of a model bile acid, taurocholate (TCA), in SCHH. In addition, changes in the protein expression of TCA uptake and efflux transporters were investigated. SCHH were treated with 1 µM OCA, 100 µM CDCA, or vehicle control for 72 hours followed by quantification of deuterated TCA uptake and efflux over time in Ca2+-containing and Ca2+-free conditions (n = 3 donors). A mechanistic pharmacokinetic model was fit to the TCA mass-time data to obtain estimates for total uptake clearance (CLUptake), total intrinsic basolateral efflux clearance (CLint,BL), and total intrinsic biliary clearance (CLint,Bile). Modeling results revealed that FXR agonists significantly increased CLint,BL by >6-fold and significantly increased CLint,Bile by 2-fold, with minimal effect on CLUptake. Immunoblotting showed that protein levels of the basolateral transporter subunits organic solute transporter α and β (OSTα and OSTβ) in FXR agonist-treated SCHH were significantly induced by >2.5- and 10-fold, respectively. FXR agonist-mediated changes in the expression of other TCA transporters in SCHH were modest. In conclusion, this is the first report demonstrating that OCA and CDCA increased TCA efflux in SCHH, which contributed to reduced intracellular TCA concentrations. Increased basolateral efflux of TCA was consistent with increased OSTα/β protein expression in OCA- and CDCA-treated SCHH.
Moons and Tides in the Battle of Marathon, Paul Revere’s Midnight Ride, and the Sinking of the Titanic

Astronomical analysis can help to determine the dates of important historical events in ancient times and also help us to solve mysteries about more recent events for which the dates are known. Our Texas State group used calculations of tide levels, lunar phase, and the direction of moonlight to derive new results for the five examples described in this chapter.
Failure detection and reactive teaming for behavior-based subsumption

Fast, lightweight intelligent controllers make it possible to apply agent-based artificial intelligence to even highly resource-constrained systems. Reactive controlmethods can provide this capability, and are frequently used in applications such as real-time games and robotics. Unfortunately, reactive controllers may not deal well with errors, as they cannot fall back on a planner to deal with unexpected situations. This limitation makes them more susceptible to certain types of failures than deliberative techniques. In this paper, we describe how four major types of failures can be detected in reactive controllers. We show how this can lead to extensions for behavior-based subsumption which allow more robust single agents, enable inexpensive multi-agent coordination, and improve agent design tools.
Trends in Postoperative Opioid Prescribing in Outpatient Pediatric Surgery.

OBJECTIVE To determine trends in opioid prescribing for home use after pediatric outpatient surgery. DESIGN Retrospective analysis of a de-identified database. SETTING Multispecialty children's hospital and freestanding surgery centers. PATIENTS, PARTICIPANTS A total of 65,190 encounters of pediatric outpatient surgeries from 2013 through 2017 for nine different surgical specialties. Patients in the cardiothoracic service and nonpainful procedures were excluded. MAIN Outcome Measures. Incidence rate of prescribing, dose, number of doses available (i.e., duration of therapy), and maximum weight-based home opioid availability from 2013 to 2017. Additional independent variables included sex, age, weight, race/ethnicity, insurance type (private vs public), and surgical service. RESULTS The incidence rate of receiving a take-home opioid prescription at discharge ranged from 18% to 21% between 2013 and 2017, with no clear directional trend. Among patients prescribed opioids, however, the maximum available take-home dose steadily declined from 2013 through 2017 (P < 0.001). This was due to both a decrease in the number of doses prescribed (i.e., duration of treatment) and, beginning in 2015, the amount per dose. Females were more likely to receive an opioid than males, and patients with public insurance were more likely to receive an opioid than those with private insurance. Opioid prescribing was more likely in patients who did not disclose their ethnicity and those of ethnic minority compared with white patients (all P < 0.0001). CONCLUSIONS The rate of receiving a take-home opioid prescription and the dose prescribed remained stable from 2013 to 2017, but the duration of treatment steadily declined, and beginning in 2015, the amount per dose also decreased. Certain subgroups of patients were more likely to be prescribed opioids and will require further investigation and confirmation.
How money drives US congressional elections: Linear models of money and outcomes

Abstract This paper analyzes whether money influences election outcomes. Using a new and more comprehensive dataset built from government sources, the paper shows that the relations between money and votes cast for major parties in elections for the U.S. Senate and House of Representatives from 1980 to 2018 are well approximated by straight lines. It then considers possible challenges to this “linear model” of money and elections on statistical grounds, resting on possible endogeneity arising from reciprocal causation between, for example, popularity and votes. The paper develops a spatial Bayesian latent instrumental variable model to tackle this much discussed problem. It checks its results by studying relations between changes in gambling odds and contributions in key elections. Both approaches suggest that reciprocal causation may happen to some degree, but that money’s independent influence on elections remains powerful.
Hyperpolarized Metabolic Imaging Detects Latent Hepatocellular Carcinoma Domains Surviving Locoregional Therapy.

Background and aims Advances in cancer treatment have improved survival; however, local recurrence and metastatic disease-the principal causes of cancer mortality-have limited the ability to achieve durable remissions. Local recurrences arise from latent tumor cells that survive therapy and are often not detectable by conventional clinical imaging techniques. Local recurrence after transarterial embolization (TAE) of hepatocellular carcinoma (HCC) provides a compelling clinical correlate of this phenomenon. In response to TAE-induced ischemia, HCC cells adapt their growth program to effect a latent phenotype that precedes local recurrence. Approach and results In this study, we characterized and leveraged the metabolic reprogramming demonstrated by latent HCC cells in response to TAE-induced ischemia to enable their detection in vivo using dynamic nuclear polarization (DNP) magnetic resonance spectroscopic imaging (MRSI) of 13 carbon-labeled substrates. Under TAE-induced ischemia, latent HCC cells demonstrated reduced metabolism and developed a dependence on glycolytic flux to lactate. Despite the hypometabolic state of these cells, DNP-MRSI of 1-13 C-pyruvate and its downstream metabolites, 1-13 C-lactate and 1-13 C-alanine, predicted histological viability. Conclusions These studies provide a paradigm for imaging latent, treatment-refractory cancer cells, suggesting that DNP-MRSI provides a technology for this application.
Formation of a β-barrel membrane protein is catalyzed by the interior surface of the assembly machine protein BamA

The β-barrel assembly machine (Bam) complex in Gram-negative bacteria and its counterparts in mitochondria and chloroplasts fold and insert outer membrane β-barrel proteins. BamA, an essential component of the complex, is itself a β-barrel and is proposed to play a central role in assembling other barrel substrates. Here, we map the path of substrate insertion by the Bam complex using site-specific crosslinking to understand the molecular mechanisms that control β-barrel folding and release. We find that the C-terminal strand of the substrate is stably held by BamA and that the N-terminal strands of the substrate are assembled inside the BamA β-barrel. Importantly, we identify contacts between the assembling β-sheet and the BamA interior surface that determine the rate of substrate folding. Our results support a model in which the interior wall of BamA acts as a chaperone to catalyze β-barrel assembly.
Decorating 3D Printed Scaffolds with Electrospun Nanofiber Segments for Tissue Engineering

Repairing large tissue defects often represents a great challenge in clinics due to issues regarding lack of donors, mismatched sizes, irregular shapes, and immune rejection. 3D printed scaffolds are attractive for growing cells and producing tissue constructs because of the intricate control over pore size, porosity, and geometric shape, but the lack of biomimetic surface nanotopography and limited biomolecule presenting capacity render them less efficacious in regulating cell responses. Herein, a facile method for coating 3D printed scaffolds with electrospun nanofiber segments is reported. The surface morphology of modified 3D scaffolds changes dramatically, displaying a biomimetic nanofibrous structure, while the bulk mechanical property, pore size, and porosity are not significantly compromised. The short nanofibers-decorated 3D printed scaffolds significantly promote adhesion and proliferation of pre-osteoblasts and bone marrow mesenchymal stem cells (BMSCs). Further immobilization of bone morphogenetic protein-2 mimicking peptides to nanofiber segments-decorated 3D printed scaffolds show enhanced mRNA expressions of osteogenic markers Runx2, Alp, OCN, and BSP in BMSCs, indicating the enhancement of BMSCs osteogenic differentiation. Together, the combination of 3D printing and electrospinning is a promising approach to greatly expand the functions of 3D printed scaffolds and enhance the efficacy of 3D printed scaffolds for tissue engineering.
Deficiency of Dietary Fiber in Slc5a8-Null Mice Promotes Bacterial Dysbiosis and Alters Colonic Epithelial Transcriptome towards Proinflammatory Milieu

Inflammatory bowel disease (IBD) is characterized by chronic inflammation in the intestinal tract due to disruption of the symbiotic relationship between the host immune system and microbiota. Various factors alter the gut microbiota which lead to dysbiosis; in particular, diet and dietary fibers constitute important determinants. Dietary fiber protects against IBD; bacteria ferment these dietary fibers in colon and generate short-chain fatty acids (SCFAs), which mediate the anti-inflammatory actions of dietary fibers. SLC5A8 is a high-affinity transporter in the apical membrane of colonic epithelium which mediates the entry of SCFAs from the lumen into cells in Na+-coupled manner. Due to the unique transport kinetics, the function of the transporter becomes important only under conditions of low dietary fiber intake. Here, we have examined the impact of dietary fiber deficiency on luminal microbial composition and transcriptomic profile in colonic epithelium in wild-type (WT) and Slc5a8-null (KO) mice. We fed WT and KO mice with fiber-containing diet (FC-diet) or fiber-free diet (FF-diet) and analyzed the luminal bacterial composition by sequencing 16S rRNA gene in feces. Interestingly, results showed significant differences in the microbial community depending on dietary fiber content and on the presence or absence of Slc5a8. There were also marked differences in the transcriptomic profile of the colonic epithelium depending on the dietary fiber content and on the presence or absence of Slc5a8. We conclude that absence of fiber in diet in KO mice causes bacterial dysbiosis and alters gene expression in the colon that is conducive for inflammation.
Macrophages: First Innate Immune Responders to Nanomaterials

Macrophages are professional phagocytes that play key roles in immune surveillance and host defense against a variety of external stimuli, including engineered nanomaterials (ENMs). Physicochemical characteristics of ENMs such as size, shape, and surface charge are factors that determine macrophage recognition and uptake through various endocytotic mechanisms. Moreover, toll-like receptors (TLRs) and scavenger receptors (SRs) on the surface of macrophages facilitate binding, uptake, and intracellular signaling in response to specific types of ENMs. Biocorona formation further modulates the interaction of ENMs with cell-surface receptors. The immune response of macrophages to ENMs, including inflammasome activation and alternative polarization, plays important roles in immune-mediated diseases such as fibrosis, asthma, and cancer.
Outcomes of isolated inframalleolar interventions for chronic limb-threatening ischemia in diabetic patients

Abstract Background Inframalleolar disease is present in many diabetic patients presenting with tissue loss. The aim of this study was to examine the patient-centered outcomes after isolated inframalleolar interventions. Methods A database of patients undergoing lower extremity endovascular interventions for tissue loss (critical limb-threatening ischemia, Wound, Ischemia, and foot Infection [WIfI] stage 1-3) and a de novo intervention on the index limb between 2007 and 2017 was retrospectively queried. Those patients with isolated inframalleolar interventions on the dorsalis pedis and medial and lateral tarsal arteries were identified. Patients with concomitant superficial femoral artery and tibial interventions were excluded. Intention-to-treat analysis by patient was performed. Patient-oriented outcomes of clinical efficacy (absence of recurrent symptoms, maintenance of ambulation, and absence of major amputation), amputation-free survival (AFS; survival without major amputation), and freedom from major adverse limb events (above-ankle amputation of the index limb or major reintervention [new bypass graft, jump or interposition graft revision]) were evaluated. Results There were 109 patients (48% male; average age, 65 years; 153 vessels) who underwent isolated inframalleolar interventions for tissue loss. All patients had diabetes, and 53% had chronic renal insufficiency (47% of these were on hemodialysis). The majority of the patients had WIfI stage 3 disease. Technical success was 81%, with a median of one vessel treated per patient. Thirty-four percent of interventions were a direct revascularization of the intended angiosome in the foot. The 30-day major adverse cardiovascular event rate was 0%. The majority of patients underwent some form of planned forefoot surgery (single digit, multiple digits, ray or transmetatarsal amputation). Wound healing at 3 months in those not requiring amputation was 76%. Predictors for wound healing were improved pedal runoff score ( Conclusions Inframalleolar intervention can be successfully performed in high-risk limbs with acceptable short-term results. However, long-term AFS remains poor because of the underlying disease process.
Documentary resistance: social change and participatory media: by Angela J. Aguayo, New York, Oxford University Press, 2019, 280 pp., US$29.95, ISBN 0-19-067625-6

In what capacity does the documentary engage in public dialogue for creating social change? Conditioned by the broadly shared ontological understanding of documentary's indexicality to the lived wo...
Propensity-score Matched Comparison of Salvage Chemotherapy Regimens in Relapsed/Refractory Acute Myeloid Leukemia.

Abstract Background Relapsed/refractory acute myeloid leukemia (AML) confers a poor prognosis, and there is no single standard of care first-line salvage regimen. FLAG (fludarabine, cytarabine, and granulocyte colony-stimulating factor) is a common salvage regimen with a favorable toxicity and efficacy profile in poor-risk AML. Materials and Methods We conducted a single-center, retrospective analysis of first relapse/primary refractory patients with AML that received salvage chemotherapy from January 2009 to July 2019. We propensity-score matched patients 1:1 (based on age at diagnosis, cytogenetic risk group, Charlson comorbidity index, de novo vs. secondary AML, and whether or not they received an allogeneic stem cell transplant in first complete remission) into 2 groups, FLAG (Group 1) or non-FLAG (Group 2) as first-line salvage regimen, with 66 patients in each group. The primary endpoint was overall response rate (complete response and complete response with incomplete hematologic recovery). Results The median patient age was 59 years (range, 19-80 years). Patients treated with FLAG had a higher overall response rate (complete response/complete response with incomplete hematologic recovery) (71.2% vs. 50.0%; odds ratio, 2.47; 95% confidence interval [CI], 1.21-5.08; P = .013), longer event-free survival (8.9 vs. 2.1 months; hazard ratio [HR], 0.58; 95% CI, 0.39-0.86; P = .005), and longer overall survival (14.2 vs. 5.9 months; HR, 0.62; 95% CI, 0.41-0.93; P = .019). Patients who received FLAG had a shorter median duration of neutropenia (22 vs. 34 days; HR, 0.43; 95% CI, 0.29-0.64; P Conclusion This analysis supports the FLAG regimen as an effective and well-tolerated salvage therapy for patients with relapsed/refractory AML.
Restraining CDK1–cyclin B activation: PP2A on the cUSP(7)

USP7 inhibitors are gaining momentum as a therapeutic strategy to stabilize p53 through their ability to induce MDM2 degradation. However, these inhibitors come with an unexpected p53-independent toxicity, via an unknown mechanism. In this issue of The EMBO Journal, Galarreta et al report how inhibition of USP7 leads to re-distribution of PP2A from cytoplasm to nucleus and an increase of deleterious CDK1-dependent phosphorylation throughout the cell cycle, revealing a new regulatory mechanism for the progression of S-phase cells toward mitosis to maintain genomic integrity.