cssi/SciSciGPT-SciSciNet huggingface dataset:
Erdheim Chester Disease treated successfully with cladribine

A 61-year-old previously healthy male with a history of progressive fatigue, lower extremity edema, and dyspnea for 4 months was hospitalized with pericardial and pleural effusions (Figure 1A, B). Lung, pleural, and pericardial biopsies were consistent with Erdheim-Chester disease. He was treated with systemic steroids, and ultimately tried on PEG-interferon. He deteriorated clinically and the disease progressed to include CNS manifestations. Ultimately he was treated with Cladribine, at a dose 0.014 mg/kg on day 1, followed by 0.09 mg/kg/day = 6.4 mg IV for 6 additional days. He received 2 further cycles of 0.14 mg kg/day for 7 days (1 month apart). After 3 cycles he improved significantly both clinically and radiographically. Six months post-treatment objective testing showed improvement in cardiac, neurologic, and pulmonary disease. Erdheim Chester Disease (ECD) is a rare non Langerhans cell histiocytosis. Only several hundred cases have been reported in the literature. Treatment for ECD is reserved for those with symptomatic disease, asymptomatic CNS involvement, or evidence of organ dysfunction. There is no standard treatment regimen: Current options include corticosteroids, Interferon alpha (IFN), systemic chemotherapy, and radiation therapy. The occurrence of the V600EBRAF mutation in about 50% of patients can make these patients amenable to targeted therapy with BRAF kinase inhibitors (e.g. Vemurafenib). More recently the presence of N/KRAS, and PIK3CA mutations have provided further rational for targeted therapies. The cytokine profile in patients with ECD suggests monocyte activation cladribine, a purine analogue toxic to monocytes, has also been studied as a treatment for ECD, especially in patients who test negative for the BRAF mutation.
Molecular Insight Into the Energy Levels at the Organic Donor/Acceptor Interface: A Quantum Mechanics/Molecular Mechanics Study

We present an investigation of the band levels and charge transfer (CT) states at the interface between two organic semiconductors, metal-free phthalocyanine (H2Pc) and 3,4,9,10-perylenetetracarboxylic bisbenzimidazole (PTCBI), using a combined quantum mechanics/molecular mechanics (QM/MM) technique. Near the organic–organic interface, significant changes from the bulk, as large as 0.2 eV, are found in the excited state energies, ionization potentials, and electron affinities, due to differences in molecular packing and polarizabilities of the two molecules. The changes in the ionization potential and electron affinity cause the CT states at the interface to be on average higher in energy than fully separated charges in the bulk materials despite having a typical local binding energy of 0.15 eV. Furthermore, we find that thermal fluctuations can induce variations of up to 0.1 eV in the CT binding energy. These results suggest that it is possible for bound interfacial CT states to dissociate in a barrierle...
Effect Analysis of AIDS Peer Education

[Objective] To improve the entertainment female sex workers (hereinafter referred to as CSW) on AIDS awareness and knowledge level of condom use,to change their high-risk behavior,and to curb AIDS epidemic in high-risk groups.[Methods]The CSW with a certain appeal in entertainment places were recruited as peer educators to establish peer education core group. Through the education on other CSW by the recruiters,the assessment was implemented after 10 months.[Results]The awareness rate of AIDS among CSW increased from 47.3% before intervention to 72.8% after the intervention. Condom using rate in recent 3 times of high-risk behavior increased from 43.5% to 63.2%.[Conclusion]The effect of peer education and comprehensive intervention among CSW is obvious,and the method can be used widely.
Colonoscopy: technique and training methods.

The endoscopist’s chief goal is to reach the cecum with the shortest length of scope and without discomfort to the patient. This is done by telescoping, shortening, and straightening the colon. The scope can be advanced directly into the visualized lumen or the lumen can be brought into view utilizing torque and withdrawal techniques. The authors describe in detail the techniques for visualizing the anus, rectum, rectosigmoid junction, sigmoid, and descending colon.
Percent area coverage through image analysis

The notion of percent area coverage (PAC) has been used to characterize surface cleanliness levels in the spacecraft contamination control community. Due to the lack of detailed particle data, PAC has been conventionally calculated by multiplying the particle surface density in predetermined particle size bins by a set of coefficients per MIL-STD-1246C. In deriving the set of coefficients, the surface particle size distribution is assumed to follow a log-normal relation between particle density and particle size, while the cross-sectional area function is given as a combination of regular geometric shapes. For particles with irregular shapes, the cross-sectional area function cannot describe the true particle area and, therefore, may introduce error in the PAC calculation. Other errors may also be introduced by using the lognormal surface particle size distribution function that highly depends on the environmental cleanliness and cleaning process. In this paper, we present PAC measurements from silicon witness wafers that collected fallouts from a fabric material after vibration testing. PAC calculations were performed through analysis of microscope images and compare them to values derived through the MIL-STD-1246C method. Our results showed that the MIL-STD-1246C method does provide a reasonable upper bound to the PAC values determined through image analysis, in particular for PAC values below 0.1.
Current clinical trials testing the combination of immunotherapy with radiotherapy

Increasing evidence demonstrates that radiation acts as an immune stimulus, recruiting immune mediators that enable anti-tumor responses within and outside the radiation field. There has been a rapid expansion in the number of clinical trials harnessing radiation to enhance antitumor immunity. If positive, results of these trials will lead to a paradigm shift in the use of radiotherapy. In this review, we discuss the rationale for trials combining radiation with various immunotherapies, provide an update of recent clinical trial results and highlight trials currently in progress. We also address issues pertaining to the optimal incorporation of immunotherapy with radiation, including sequencing of treatment, radiation dosing and evaluation of clinical trial endpoints.
Laboratory air-entraining breaking waves: Imaging visible foam signatures to estimate energy dissipation

Oceanic air-entraining breaking waves fundamentally influence weather and climate through bubble-mediated ocean–atmosphere exchanges, and influence marine engineering design by impacting statistics of wave heights, crest heights, and wave loading. However, estimating individual breaking wave energy dissipation in the field remains a fundamental problem. Using laboratory experiments, we introduce a new method to estimate energy dissipation by individual breaking waves using above-water images of evolving foam. The data show the volume of the breaking wave two-phase flow integrated in time during active breaking scales linearly with wave energy dissipated. To determine the volume time-integral, above-water images of surface foam provide the breaking wave timescale and horizontal extent of the submerged bubble plume, and the foam decay time provides an estimate of the bubble plume penetration depth. We anticipate that this novel remote sensing method will improve predictions of air-sea exchanges, validate models of wave energy dissipation, and inform ocean engineering design.
Leukemic B Cells from CD38 Positive but Not CD38 Negative B-CLL Patients Express Heightened Levels of Cell Cycle Related Genes.

Within the past five years studies published from this laboratory and others have identified or confirmed CD38 as a marker for aggressive disease in B cell chronic lymphocytic leukemia (B-CLL). To learn more about the possible role of CD38 in this disease, we performed gene expression profiling (GEP; Affymetrix U133A platform) on primary leukemic B cells isolated from CD38 positive and negative patients. We and others have previously shown that the leukemic compartment within some patients consists of both CD38neg and CD38pos CLL B cells. To optimize identification of differentially expressed genes associated with CD38 expression or lack thereof, we restricted our gene profiling to patient cells that were unimodally negative for CD38 and those that expressed unimodally high levels of CD38. In both groups of patients, CD19 positive cells were purified using magnetic bead cell sorting on a Miltenyi AutoMacs prior to isolation of total RNA. To determine genes that appear to be differentially expressed in this set of experiments, we used a recently developed model-based algorithm that uses the normalized probe-level data as well as information about the underlying experimental design. Reassuringly, the gene expression profiles within the CD38pos versus the CD38neg cohort maintain congruency within each cohort when analyzing the gene expression data set as a whole, as well as within categories such as adhesion, signaling, and transcriptional molecules. Using this analytical approach, several genes emerged as interesting candidates for exploration into the nature of the CD38pos association with disease aggressiveness. Interestingly, although peripheral blood CLL B cells are overwhelmingly in the resting, G0, stage of the cell cycle, several cell cycle related genes were expressed at higher levels in CD38pos patient leukemic cells but not in CD38neg leukemic patients. Moreover, these genes encompass protein families that function at different stages throughout the cell cycle. These genes include: anaphase promoting complex subunit 5 (APC5); cell division cycle (cdc) family members; a checkpoint protein CHFR; the microtubule and actin associated protein, MACF1; the mitotic spindle checkpoint protein, MAD1L1; the DNA replication regulator, MCM7; STAG3, a meiotic regulator of chromosome segregation; and several activators of the ubiquitin pathway, including UBE2N, a known regulator of DNA repair enzymes (p-values of
Learning-related cognitive self-regulation measures for prekindergarten children: A comparative evaluation of the educational relevance of selected measures.

Many cognitive self-regulation (CSR) measures are related to the academic achievement of prekindergarten children and are thus of potential interest for school readiness screening and as outcome variables in intervention research aimed at improving those skills in order to facilitate learning. The objective of this study was to identify learning-related CSR measures especially suitable for such purposes by comparing the performance of promising candidates on criteria designed to assess their educational relevance for pre-K settings. A diverse set of 12 easily administered measures was selected from among those represented in research on attention, effortful control, and executive function, and applied to a large sample of pre-K children. Those measures were then compared on their ability to predict achievement and achievement gain, responsiveness to developmental change, and concurrence with teacher ratings of CSR-related classroom behavior. Four measures performed well on all those criteria: Peg Tapping, Head-Toes-Knees-Shoulders, the Kansas Reflection-Impulsivity Scale for Preschoolers, and Copy Design. Two others, Dimensional Change Card Sort and Backwards Digit Span, performed well on most of the criteria. Cross-validation with a new sample of children confirmed the initial evaluation of these measures and provided estimates of test–retest reliability. (PsycINFO Database Record (c) 2017 APA, all rights reserved)
Chapter 10 – Cancer Epigenetics

Epigenetic studies reveal important insights into cancer biology. This chapter presents a broad picture of how epigenetic changes in health and disease and in response to environment contribute to carcinogenesis, and how findings from newer approaches and emergent technologies may extend these observations. Consideration is given to biological insights drawn from studies of epigenomic patterns in cancer cells, and the influence of epigenomic profiling on diagnosis, therapy, and prognosis. The chapter begins with a brief overview of the concepts and foundations on which epigenetics is built and concludes with comments on prospects for the future of cancer epigenetics.
Time effect of rutaecarpine on caffeine pharmacokinetics in rats.

Abstract Rutaecarpine is reported as a potent inducer of CYP1A2 enzyme in rats. There are natural herbal supplements containing rutaecarpine that are designed to enhance the CYP1A2-dependent removal of caffeine from blood so that people can have coffee later in the day without causing sleep interference. This study aimed to determine the minimum amount of time needed from oral rutaecarpine administration until the observed effect of rutaecarpine on caffeine pharmacokinetics (PK) in 15 male Sprague-Dawley rats. PK parameters for caffeine and its metabolites in the control and rutaecarpine groups were calculated using WinNonlin®. Results showed that orally administered rutaecarpine at 100 mg/kg dose as early as 3 h before oral caffeine administration significantly decreased the oral systemic exposure and mean residence time of caffeine and its metabolites due to decreased caffeine bioavailability (by up to 75%) and increased clearance. The systemic exposure of caffeine and its metabolites were also decreased when caffeine was given intravenously, though this effect was less pronounced than when caffeine was given orally. Although plasma level of rutaecarpine was undetectable (less than 10 ng/mL), rutaecarpine still induced hepatic CYP1A2 activity. Results from 7-methoxyresorufin O-demethylation activity, which is specific to CYP1A2, showed that 3 h after one rutaecarpine oral dose, CYP1A2 activity in rat liver tissue was increased by 3- fold. This finding suggested that rutaecarpine effectively induced CYP1A2 activity in the liver.
Submesoscale processes at shallow salinity fronts in the Bay of Bengal : observations during the winter monsoon

AbstractLateral submesoscale processes and their influence on vertical stratification at shallow salinity fronts in the central Bay of Bengal during the winter monsoon are explored using high-resol...
Federally employed physician assistants.

ABSTRACT The federal government is the largest single employer of clinically active physician assistants (PAs) in the United States, with >3,000 PAs in 2008. PAs are present within the Departments of Defense, Veterans Affairs, Health and Human Services, Justice, and Homeland Security. Most are civil servants or hold a commission in the uniformed services. Most employing agencies have expanding needs for PAs. This overview presents a framework of how PAs are being used and the critical roles they play in the federal health care system. Because civilian job opportunities for PAs are plentiful, the federal system is seeking strategies for recruitment and retention. A centralized plan may be one useful recommendation.
King, Queen, Master, Slave: The Master/slave Dialectic & the Thousand and One Nights

Previous critical analyses of the Frame Story of The 1001 Nights, the story of Shahrazad and King Shahriyar, have overlooked the importance of the slave's role in the narrative of betrayal and revenge. This article makes use of Hegel's master/slave dialectic, in particular as that dialectic is reflected in the work of Jacques Lacan, to understand the critical role played by the slave in the story. It shows that the roles of master and slave are not fixed with any characters, but rather are occupied successively by different characters. Shahriyar's crisis is seen as an imaginary deadlock in Lacanian terms. Shahrazad, who refuses the role of the slave, breaks the deadlock and introduces him into the symbolic order. Her means of doing this, her method of narration, may be compared to Freud's Fort/Da game.
Physiologic changes during pregnancy

Pregnancy induces profound changes in the physiologic systems of women that are essential to support the growing fetus and the pregnant mother. These include increases in maternal cardiac output and blood flow to vital organs, particularly the uteroplacental unit, decrease in systemic vascular resistance and blood pressure, expansion of the maternal blood volume to a larger degree than the increase in erythrocyte mass, leading to hemodilution and physiologic anemia, and increase in pulmonary minute ventilation and tidal volume. Moreover, maternal total body water increases and plasma protein concentrations (notably albumin) decrease. Gastric emptying and gastrointestinal motility are delayed while the glomerular filtration rate and renal plasma flow increase. Insulin, glucose, and fatty acids metabolism undergoes changes to facilitate placental glucose transfer. Knowledge of these and other changes of pregnancy, and their profound impact on the pharmacodynamics and pharmacokinetics of drugs taken during pregnancy, are essential for diagnosis and treatment of medical conditions in order to optimize maternal and fetal health.
Author Correction: Distinguishing genetic correlation from causation across 52 diseases and complex traits

In the version of this article originally published, there were errors in equations. In the HTML and PDF, the initial term of equation 10 was estimated GCP but should have been estimated standard error, while a 'hat' was missing from the first alpha in the second term of the expression at the end of the paragraph following equation (6) in the Methods. In addition, in the abstract in the PDF, a subscript 1 was used instead of a subscript 2 for the final term of the first fourth-moment expression. These errors have been corrected in the HTML, PDF and print versions of the paper.
New atrial fibrillation diagnosed by 30-day rhythm monitoring.

Background Recent studies of patients with pacemakers and implantable cardioverter/defibrillators have shown that subclinical atrial fibrillation (AF) is common and is associated with thromboembolic risk. We sought to evaluate the frequency, characteristics, and impact of new AF diagnosed by ambulatory 30-day rhythm monitoring. Methods The 30-day rhythm monitoring data from January 2010 to August 2015 at our institution were reviewed. Medical record review was performed on patients that had a new or preexisting diagnosis of AF. Results Of 2,326 patients without a previous diagnosis of AF, 78 had a new diagnosis of AF (3.4%) during 30-day monitoring. Patients with a new diagnosis of AF (mean age of 68.5 years, 56% female) had a mean CHA2DS2-VASc score of 3.2 (±1.8). The median time to diagnosis was 6 days, and 86% were diagnosed within 14 days. In 31 patients (40%), AF was exclusively detected automatically by the monitor. Of 46 patients that had manually activated the monitor, 34 also had automatically detected AF. Each patient had a median of 7 episodes, with the median duration of the longest episode being approximately 2 hours. Following the diagnosis of AF, 37 (47%) were started on anticoagulation and 9 (12%) were prescribed aspirin. Conclusions A total of 3.4% of patients who underwent 30-day rhythm monitoring for any indication were found to have a new diagnosis of AF (402 per 1000 patient-years). Most of these episodes were detected automatically, corresponding to device-detected subclinical AF. The most common intervention following diagnosis of AF was initiation of oral anticoagulation.
Land of Opportunity: Life Beyond Hollywood Movies

One of the most dynamic demographic transitions that have been shaping and reshaping the population characteristics of various countries in recent years is that of human migration. Since many years, United States has been seen as the land of opportunity by millions of people. It attracts people from across the world due to economic, political, and social reasons resulting in migration to United States.
Hexagonal-WO3 nanorods encapsulated in nitrogen and sulfur co-doped reduced graphene oxide as a high-performance anode material for lithium ion batteries

Abstract Nanocomposites consisting of hexagonal WO3 nanorods embedded into nitrogen, sulfur co-doped reduced graphene oxide nanosheets (h-WO3/NSG) have been synthesized through a combination of ultrasonic processing and hydrothermal reactions. The nanocomposite containing 54 ​wt% of (N, S)-doped reduced graphene oxide shows an excellent discharge capacity of 1030 mAh g-1 at the first cycle and high rate capacities ranging from 513 to 150 mAh g-1 at the current density ranging from 100 to 2000 ​mA ​g-1, respectively. In addition, the synthesized WO3/NSG nanocomposite also exhibits remarkable cycle stability with a high discharge capacity of 196 mAh g-1 at the current density of 1500 ​mA ​g-1 for 200 cycles. The excellent electrochemical performance of h-WO3/NSG nanocomposite can be attributed to synergistic contributions from (1) the small size of WO3 nanorods, which increases the contact surface area with the electrolyte, effectively shortening the diffusion length of Li+ ions leading to high Li+ incorporation within h-WO3; (2) the structural support provided by the NSG matrix, which alleviates the large volume change of WO3 nanorods during Li+ insertion/extraction; and (3) the large numbers of surface defects provided by nitrogen and sulfur co-dopants, which serve as channels to improve the Li+ diffusion. Furthermore, electrochemical impedance spectroscopy (EIS) measurement demonstrates that nitrogen, sulfur co-doped reduced graphene oxide can reduce the electrochemical impedance of the electrode, further improving the electrochemical performance of the anode. This study provides important strategies for the design of future high performance anode materials for lithium ion battery.
Reply re: "Evaluation of Electronic Health Record Implementation in an Academic Oculoplastics Practice".

PURPOSE Despite increasing electronic health record (EHR) adoption, perceptions of EHRs are negative among ophthalmologists due to concerns about productivity, costs, and documentation. The authors evaluated the effects of EHR adoption in an oculoplastics practice, which had not been previously studied. METHODS Clinical volume, documentation time, time spent with patients, reimbursement, relative value units, and patient satisfaction were examined for 2 academic oculoplastics attendings between April 2018 and April 2019, with EHR implementation in September 2018. RESULTS The mean number of patients seen in a half-day clinic was 31.8 versus 27.7 (p = 0.018) pre- and post-EHR implementation, respectively. EHR implementation had no effect on total monthly reimbursement (p = 0.88) or total monthly relative value units (p = 0.54). Average reimbursement (p = 0.004) and relative value units (p = 0.001) per patient encounter were significantly greater with EHR use. Patient satisfaction scores improved (p = 0.018). Mean physician time per patient increased from 6.4 to 9.0 minutes (p < 0.001). Mean documentation time per patient increased from 1.7 to 3.6 minutes (p < 0.001). Average patient wait times decreased by 9 minutes (p = 0.03) with EHR use. No scribes were used. CONCLUSIONS EHR implementation was associated with decreased patient volume without significant differences in total reimbursement. Although EHR adoption was associated with increased physician time devoted to patients and greater time expenditure on documentation, patients experienced decreased wait times. This suggests that EHR use streamlined the overall clinic flow without sacrificing physicians' time with the patient. The author's findings suggest that EHR implementation can be accomplished in an academic oculoplastics setting without negative impact on patient experience or reimbursement considerations.
Relationship of household cooking salt and eating out on iodine status of pregnant women in environmental iodine-deficient coastal areas of China

As city residents eat out more frequently, it is unknown that if iodised salt is still required in home cooking. We analysed the relationship of household salt and eating out on urinary iodine concentration (UIC) in pregnant women. A household condiment weighing method was implemented to collect salt data for a week. A household salt sample was collected. A urine sample was taken at the end of the week. Totally, 4640 participants were investigated. The median UIC was 139·1 μg/l in pregnant women and 148·7, 140·0 and 122·9 μg/l in the first, second and third trimesters. Median UIC in the third trimester was lower than in the other trimesters (P < 0·001). The usage rates of iodised (an iodine content ≥ 5·0 mg/kg) and qualified-iodised (an iodine content ≥ 21·0 mg/kg) salt were 73·9 and 59·3 %. The median UIC in the qualified-iodised salt group was higher than in the non-iodised group (P = 0·037). The median UIC in the non-iodised group who did not eat out was lower than in qualified-salt groups who both did and did not eat out (P = 0·007, <0·001). The proportion of qualified-iodised salt used in home cooking is low, but foods eaten out have universal salt iodisation according to the national compulsory policy. Household iodised salt did not play a decisive role in the iodine status of pregnant women. Pregnant women in their third trimester who are not eating out and using non-iodised salt at home require extra iodine.
Best reoperative strategy for failed fundoplication: redo fundoplication or conversion to Roux-en-Y gastric diversion?

Failed fundoplication is a difficult reoperative challenge, with limited evidence differentiating outcomes of a redo fundoplication versus conversion to Roux-en-Y anatomy with a gastric diversion (RYGD). The aim of this study was to determine the impact of these reoperative strategies on symptom resolution. A retrospective single institution study of patients with failed fundoplications undergoing conversion to RYGD or redo fundoplication between 2006 and 2019 was conducted. Patient characteristics, preoperative evaluation, operative findings, and postoperative outcomes were recorded and analyzed. 180 patients with symptomatic, failed fundoplications were identified: 101 patients (56.1%) underwent conversion to RYGD, and 79 patients (43.9%) underwent redo fundoplication. Body mass index (BMI) was significantly higher for the patients undergoing RYGD with mean BMI of 34.3 ± 6.9 vs 27.7 ± 3.9 kg/m2 (p < 0.001). Patients undergoing conversion to RYGD were also more comorbid than their counterparts, with higher rates of obstructive sleep apnea (17.8% vs 5.1%, p = 0.01), but similar rates of hypertension (54.5% vs 44.3%, p = 0.18, asthma/COPD (25.7% vs 16.5%, p = 0.13), diabetes (10.9% vs 10.1%, p = 0.87), and hyperlipidemia (29.7% vs 36.7%, p = 0.32). Mean operative times were significantly higher for the RYGD (359.6 ± 90.4 vs 238.8 ± 75.6 min, p < 0.0001), as was mean estimated blood loss (168.8 ± 207.5 vs 81.0 ± 145.4, p < 0.0001). Conversion rates from minimally invasive to open were similar (10.9% vs 11.4%, p = 0.92). The incidence of recurrent reflux symptoms was not significantly different (p = 0.46) between RYGD (16.8%) and redo fundoplication (12.8%), at an average follow-up of 50.6 ± 140.7 vs 34.7 ± 39.2 months, (p = 0.03). For the RYGD cohort, patients also had resolution of other comorbidities including obesity 35.6%, OSA 16.7%, hyperlipidemia 10.0%, hypertension 9.1%, and diabetes 9.1%. On average, patients decreased their BMI by 6.8 ± 5.5 kg/m2 and lost 69.6% of their excess body weight. Mean length of stay was higher in patients undergoing RYGD (5.3 ± 7.3 vs 3.0 ± 1.9 days, p = 0.01). Thirty-day readmission rates were similar (9.9% vs 3.8%, p = 0.12). The reoperation rate was higher in the RYGD cohort (17.8% vs 2.5%, p = 0.001). RYBG and redo fundoplication are equivalent in terms of resolution of reflux. RYGD resulted in significant loss of excess body weight.
Does Property Ownership Lead to Participation in Local Politics? Evidence from Property Records and Meeting Minutes

Homeowners and renters have participated in politics at different rates throughout American history, but does becoming a property owner motivate an individual to participate in local politics? I combine deed-level property records in California and Texas with an original dataset on individual comments in local city council meetings to study the role of property ownership in shaping costly forms of political behavior, and I document large inequalities in who participates at city council meetings. I also link property records to individual-level contribution records and administrative voter files and find that becoming a property owner increases an individual’s political activity. Over and above voting in local elections, property ownership motivates individuals to participate in local city council meetings and donate to candidates. These findings illustrate how the experience of homeownership leads property owners to become much more active in local politics.
New cut-score to improve performance of the Memory Validity Profile (MVP) in heterogenous clinical populations.

The Memory Validity Profile (MVP) is a standalone performance validity test developed specifically for use with children. Prior research has demonstrated the MVP’s strength in its ease of administr...
Placebo and Nocebo: Ethical Challenges and Solutions

The defining circumstances and reasons for promoting healing processes based on placebo and avoiding (undesirable) nocebo effects in clinical practice represent a challenge for translational and patient-oriented medicine. Exploiting placebos and placebo effects for the benefit of the patient requires a rigorous evaluation of potential benefits and harms associated with these interventions. Moreover, any attempts to harness placebo benefits and mitigate nocebo effects in clinical practice should be done consistently with professional norms and integrity, and ethical-legal requirements of informed consent. This chapter systematically discusses the complex issue of professional and ethical requirements in using placebos and placebo effects in pain-related research and practices. Within this scope, some important questions need to be addressed as well: (a) Can placebo analgesic effects produce clinically significant benefits? (b) What translational research is being done, or should be done? (c) What work is being done in this area to enable and encourage doctors to incorporate ethically the concept of placebo and nocebo effects into their work?
Exenatide Adjunct to Nicotine Patch Facilitates Smoking Cessation and May Reduce Post-Cessation Weight Gain: A Pilot Randomized Controlled Trial

INTRODUCTION Approved pharmacological treatments for smoking cessation are modestly effective, underscoring the need for improved pharmacotherapies. Glucagon-like peptide-1 receptor (GLP-1R) agonists attenuate the rewarding effects of nicotine in preclinical studies. We examined the efficacy of extended-release exenatide, a GLP-1R agonist, combined with nicotine replacement therapy (NRT, patch) for smoking cessation, craving, and withdrawal symptoms, with post-cessation body weight as a secondary outcome. METHODS Eighty-four prediabetic and/or overweight smokers were randomized (1 : 1) to once-weekly placebo or exenatide, 2 mg, subcutaneously. All participants received NRT (21 mg) and brief smoking cessation counseling. Seven-day point prevalence abstinence (expired CO level ≤5 ppm), craving, withdrawal, and post-cessation body weight were assessed following 6 weeks of treatment. A Bayesian approach for analyzing generalized linear models yielded posterior probabilities (PP) to quantify the evidence favoring hypothesized effects of treatment on the study outcomes. RESULTS Exenatide increased the risk for smoking abstinence compared to placebo (46.3% and 26.8%, respectively), (risk ratio [RR] = 1.70; 95% credible interval = [0.96, 3.27]; PP = 96.5%). Exenatide reduced end-of-treatment craving in the overall sample and withdrawal among abstainers. Post-cessation body weight was 5.6 pounds lower in the exenatide group compared to placebo (PP = 97.4%). Adverse events were reported in 9.5% and 2.3% of participants in the exenatide and placebo groups, respectively. CONCLUSIONS Exenatide, in combination with the NRT improved smoking abstinence, reduced craving and withdrawal symptoms, and decreased weight gain among abstainers. Findings suggest that the GLP-1R agonist strategy is worthy of further research in larger, longer duration studies. IMPLICATIONS Despite considerable progress in tobacco control, cigarette smoking remains the leading cause of preventable disease, disability, and death. In this pilot study, we showed that extended-release exenatide, a glucagon-like peptide-1 receptor agonist, added to the nicotine patch, improved abstinence and mitigated post-cessation body weight gain compared to patch alone. Further research is needed to confirm these initial positive results.
El rol de los sectores indígenas en la independencia del Perú. Bases para una nueva interpretación

The role of indigenous peoples in the independence process of the viceroyalty of Peru has never been clear. Some historians have claimed indigenous peoples did not play a major role, while others have referred to a staunch patriotism, in which their loyalty to the independence cause was in stark contrast to the hesitation of the elites, throughout the 1808-1824 period. Since indigenous people accounted for the majority of the population and given that they fought as soldiers in the war, I advocate moving beyond dichotomies and analysing their status as key political players of the period. By focusing on the political strategies adopted by indigenous peoples between the beginning of the monarchical crisis of 1808 and the end of the war in 1824, I will argue that indigenous peoples created a new way of doing politics that would define, and far outlast, the war of independence.
Outcomes in Head and Neck Free Flap Reconstruction Among Patients With a History of Venous Thromboembolism.

ObjectiveTo investigate if a history of venous thromboembolism (VTE) is a risk factor for complications in head and neck free flap surgery by assessing outcomes among patients with a history of dee...
Practical pain management in cows and calves

Negative public perception of pain associated with routine animal management practices such as dehorning and castration is increasing. Preemptive analgesia can be applied in advance of the painful stimulus, thereby reducing sensitization of the nervous system to subsequent stimuli that could amplify pain. Drugs that could be used to provide preemptive analgesia include local anesthetics, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, α2-agonists, and N-methyl D-aspartate receptor antagonists. Pathological pain states in cattle occur as a result of tissue damage, nerve damage, and inflammation and are frequently associated with pain hypersensitivity. Chronic pain associated with lameness is considered one of the most significant welfare concerns in dairy cows. Inflammatory pain associated with lameness responds modestly to treatment with NSAIDs, but neuropathic pain (due to nerve damage or neuronal dysfunction) is considered refractory to the effects of NSAIDs, but may respond to gabapentin. In this session we will review the analgesic drug options available for practitioners to use in the United States (US). These proceedings contain excerpts that were previously published in a 2013 (Vol. 1: pp 11-28) issue of Veterinary Clinics of North America: Food Animal Practice and readers are urged to consult this text for more detailed information on this topic.
The ASCC2 CUE domain contacts adjacent ubiquitins to recognize K63-linked polyubiquitin

Abstract Alkylation of DNA and RNA is a potentially toxic lesion that can result in mutations and cell death. In response to alkylation damage, K63-linked polyubiquitin chains are assembled that localize the ALKBH3-ASCC repair complex to damage sites in the nucleus. The protein ASCC2, a subunit of the ASCC complex, selectively binds K63-linked polyubiquitin chains using its CUE domain, a type of ubiquitin-binding domain that typically binds monoubiquitin and does not discriminate among different polyubiquitin linkage types. We report here that the ASCC2 CUE domain selectively binds K63-linked diubiquitin by contacting both the distal and proximal ubiquitin. Whereas the ASCC2 CUE domain binds the distal ubiquitin in a manner similar to that reported for other CUE domains bound to a single ubiquitin, the contacts with the proximal ubiquitin are unique to ASCC2. The N-terminal portion of the ASCC2 α1 helix, including residues E467 and S470, contributes to the binding interaction with the proximal ubiquitin of K63-linked diubiquitin. Mutation of residues within the N-terminal portion of the ASCC2 α1 helix decreases ASCC2 recruitment in response to DNA alkylation, supporting the functional significance of these interactions during the alkylation damage response.
Aligning gas regulation with climate goals: A road map for state regulators

Abstract Reduction in the usage of natural gas is critical to mitigate climate change. When combusted, natural gas usages can vary from home heating and cooking to large industrial processes to fuel for electric generation. While many states have adopted greenhouse gas (GHG) emissions targets and are conducting long-term planning for the transition away from natural gas, retail gas utilities and their regulators have generally continued to operate in a business-as-usual framework assuming static or increased natural gas usage. In most states, there is a lack of reconciliation between these two policy objectives. This paper presents recommendations for State Public Utilities Commissions (Commissions) and other regulators to align decision making regarding gas utility operations, rates and infrastructure with climate goals to drive reductions in GHG emissions. While this paper primarily focuses on states that have enacted climate laws, the recommendations are equally relevant for states without such laws, as they ultimately serve to improve regulatory oversight, protect customers from unnecessary costs, and support continued provision of safe, reliable and affordable service in an evolving industry.
Health system perspectives in acute kidney injury: commitment to kidney health and planning implementation interventions.

Purpose of review To discuss a deliberate commitment by health systems to optimize kidney health and outcomes of patients who are at risk for or develop acute kidney injury (AKI) during hospitalization. Recent findings In 2019, the US Department of Health and Human Services set national goals targeted at improving the care and outcomes of patients with kidney disease including prevention by reducing the number of Americans who develop end-stage kidney disease (ESKD) by 25% by 2030. In response to this call to action, there is a need to focus on education to identify patients at high-risk for kidney disease development and progression, active surveillance methods to ensure timely identification, offering better follow-up care after an episode of AKI. A strategic approach to determining the health systems level of commitment and developing a plan for organizational change is discussed in this commentary. Items for consideration are structuring sound implementation projects and selecting implementation interventions. Clinical interventions to consider for implementation include the use of clinical decision support for detecting patients with AKI, novel biomarkers to determine patients at high-risk for AKI and nephrotoxin stewardship to prevent medication safety complications and drug-associated AKI. Summary There is a national call to action to improve the care and outcomes of patients with kidney disease. Health systems have an opportunity to respond by providing a high level of commitment towards ensuring the best kidney health for all patients equally. Deliberate change that is sustainable and scalable should be considered by all health systems.
Dimeric Copper and Lithium Thiolates: Comparison of Copper Thiolates with Their Lithium Congeners.

The direct reactions of the large terphenyl thiols HSAriPr4 (AriPr4= -C6H3-2,6-(C6H3-2,6-iPr2)2) and HSAriPr6 (AriPr6= -C6H3-2,6-(C6H2-2,4,6-iPr3)2) with stoichiometric amounts of mesitylcopper(I) in THF at ca. 80 °C afforded the first well-characterized dimeric copper thiolato species {CuSAriPr4}2 (1) and {CuSAriPr6}2 (2) with elimination of mesitylene. The complexes 1 and 2 were characterized by NMR and electronic spectroscopy as well as by X-ray crystallography. They have dimeric Cu2S2 core structures in which the two copper atoms are bridged by the sulfurs from the thiolato ligands and feature short Cu--Cu distances near 2.4 A as well as a weak copper-flanking aryl ring interaction from a terphenyl substituent. The structures of the planar Cu2S2 cores bear a resemblance to the CuA site in nitrous oxide reductase in which two cysteines also bridge two copper atoms. The related dimeric Li2S2 structural motif was also observed in the lithium congeners {LiSAriPr4}2 (3) and {LiSAriPr6}2 (4) which were synthesized directly from the thiols and n-BuLi in hexanes. However, despite the very similar effective ionic radii of the Li+ (0.59 A) and Cu+ (0.60 A) ions, the Li--Li structures display very much longer (by more than ca. 0.5 A) separations than the corresponding Cu--Cu distances in 1 and 2, which may be due to weaker dispersion interactions.
Effects of Prolonged Ethanol Lock Exposure to Carbothane- and Silicone-based Hemodialysis Catheters: A 26-week Study:

PurposeAntibiotic locks in catheter-dependent chronic hemodialysis patients reduce the rate of catheter-related bloodstream infections (CRBSIs), but may be associated with the development of resistant bacteria. Ethanol-based catheter locks may provide a better alternative; however, there are limited data on the long-term integrity of dialysis catheters exposed to ethanol.MethodsWe performed in vitro testing of two types of hemodialysis catheters—silicone (SLC) and carbothane (CBT) based—with a 70% ethanol lock (EL) versus heparin lock (HL) for 26 weeks. Lock solutions were changed thrice weekly to mimic a conventional hemodialysis schedule. We tested mechanical properties of the catheters at 0, 13 and 26 weeks by examining stress/strain relationships (SS400%) and modulus of elasticity (ME). Electron microscopy was performed to examine catheter ultrastructure at 0 and 26 weeks.ResultsCatheter integrity for HL versus EL in SLC (SS400%: 4.5 vs. 4.5 MPa, p = NS; ME: 4.6 vs. 4.7 MPa, p = NS) or CBT-based cathe...
Inland California during the Pleistocene—Megafaunal stable isotope records reveal new paleoecological and paleoenvironmental insights

Abstract We measured oxygen and carbon isotope compositions from teeth from three fossil localities in California, The McKittrick Tar seeps (Rancholabrean), Fairmead Landfill, and Irvington (both Irvingtonian). These sites have produced a variety of megafauna fossils, and to date are relatively understudied. Previous ecological studies of Pleistocene California megafauna have focused on the coastal Rancho La Brea tar seeps (RLB), neglecting inland faunas. Both Fairmead Landfill and McKittrick are located in California's San Joaquin Valley, and provide the first isotopic data from the region. We sampled a wide range of taxa; Equus, Camelops, Mammuthus, Mammut, Hemiauchenia, Odocoileus, Tetrameryx, Capromeryx, Platygonus, Canis dirus, Canis latrans, Arctodus simus, Smilodon, Homotherium, Miracinonyx, Panthera onca and Panthera atrox. Stable carbon values from both middle Pleistocene localities are consistent with a C3 dominated environment. Mean annual precipitation (MAP) estimates for the middle Pleistocene localities are ~ 340 mm/year for Fairmead Landfill and ~ 900 mm/year for Irvington. While the inland MAP estimate is similar to modern levels, Irvington MAP estimates are significantly higher than the modern average. In contrast, the McKittrick tar seeps show clear evidence of C4 consumption among Equus, Bison and Camelops, suggesting a mixture C4 grasses and halophytes. Similarly, comparing between McKittrick and published data for RLB indicate a higher level of C4 resources inland. Serially sampled teeth from both inland localities reveal diet and resource partitioning between browsers and grazers.
Oxidative coupling. : II. The total synthesis of enterolactone

Abstract Oxidative coupling of 3-methoxyhydrocinnamic acid dianion with molecular iodine forms the key step in an efficient synthesis of enterolactone.
The unbearable transparency of Stein estimation

Charles Stein [10] discovered that, under quadratic loss, the usual unbiased estimator for the mean vector of a multivariate normal distribution is inadmissible if the dimension n of the mean vector exceeds two. On the way, he constructed shrinkage estimators that dominate the usual estimator asymptotically in n. It has since been claimed that Stein’s results and the subsequent James–Stein estimator are counter-intuitive, even paradoxical, and not very useful. In response to such doubts, various authors have presented alternative derivations of Stein shrinkage estimators. Surely Stein himself did not find his results paradoxical. This paper argues that assertions of “paradoxical" or “counter-intuitive" or “not practical" have overlooked essential arguments and remarks in Stein’s beautifully written paper [10]. Among these overlooked aspects are the asymptotic geometry of quadratic loss in high dimensions that makes Stein estimation transparent; the asymptotic optimality results that can be associate with Stein estimation; the explicit mention of practical multiple shrinkage estimators; and the foreshadowing of Stein confidence balls. These ideas are fundamental for studies of modern regularization estimators that rely on multiple shrinkage, whether implicitly or overtly.
Experiments on hydrogen at megabar pressures; Metallic hydrogen

Not only is the equation of state of molecular hydrogen at high density of interest to planetary models and laser fusion, but also the proposals that metallic hydrogen might be a superconductor at high temperature and/or metastable, has recently led to a large amount of theoretical and experimental work. Hydrogen is expected to transform into the metallic phase at a density of about 1 g/cm3, which is 14 times the normal liquid density of the molecular phase. Such a density requires a pressure of several megabars and because of its great compressibility, new approaches to compressing matter are needed. This paper will describe the experimental approaches to obtaining and studying the properties of hydrogen in the megabar region.
Changing Emphases in Spectral Classification

The definitions and general principles of the MK system given in the statement by Dr. Morgan, which Dr. McCarthy has read to you, are an expression of my views also. It is mainly in specifying the MK domains that modifications are necessary for the cooler stars - and these for rather obvious reasons. For example, the spectral range has been extended to longer wavelengths, particularly for stars showing strong molecular bands. The lines and bands in the visual and far red regions are particularly useful in defining temperature and chemical composition, but the blue region remains important as having the features most sensitive to luminosity.