cssi/SciSciGPT-SciSciNet huggingface dataset:
Civil Disobedience and the Necessity Defense

Freedom of expression in a free society includes freewheeling public dissent on controversial political issues of the day. Civil disobedience is a form of protest that, while usually peaceful, involves violating the law— usually by trespassing on government property, blocking access to buildings, or engaging in disorderly conduct. Civil disobedience has been called “the deliberate violation of law for a vital social purpose.” In their day in court, civil disobedients have at times sought to interpose the necessity defense to justify their conduct. The necessity defense asserts that breaking the law was justified in order to avert a greater harm that would occur as a result of the government policy the offender was protesting. Protestors will seek to invoke the necessity defense not so much to gain acquittal from the relatively minor charges, but to advance the more important objective of publicly airing the moral and political issues that inspired their act of civil disobedience. There is the hope of gaining notoriety for a cause by discussing it in court, and “educating” the jury about political grievances or other social harms. The strategy is meant to appeal to a higher principle than the law being violated—the necessity of stopping objectionable government policies—and to let the jury have an opportunity to weigh their technically illegal actions on the scales of justice. Acquittal is of course hoped for in the end but may be quite low on the protestors’ list of priorities.
Enterotoxins and ion transport.

Throughout the world and especially in developing countries acute diarrhoea1 diseases are the single major cause of morbidity and mortality both in humans and farm animals. Bacteria are among the chief causal agents of acute diarrhoeas and although fluid secretion can result from an increase in luminal osmolarity or hydrostatic pressure, the majority of bacterial enteropathogens appear to cause fluid loss by stimulating enterocytes to actively secrete electrolytes. Based on their ability to cause histological damage to the host intestinal epithelium, enteropathogenic bacteria can be classified as invasive or non-invasive strains. Invasive strains damage the host mucosa and cause diarrhoea by cytotoxic destruction of enterocytes and/or the induction of inflammatory responses; some strains also elaborate enterotoxins. The molecular mechanisms underlying the cytotoxic and diarrhoeagenic effects of these bacteria are not well understood, but in contrast, in recent years major advances have been made in elucidating the molecular mechanisms by which non-invasive bacteria elicit their enteropathogenic effects. These bacteria cause diarrhoea by elaborating one or more enterotoxins without histological damage to the host mucosa. The mechanisms by which these enterotoxins and their intracellular mediators regulate ion transport will be reviewed here (for the sake of brevity literature cited includes recent reviews).
Abstract IA23: Medulloblastoma subgroup-specific mutations model the tumor microenvironment

Brain tumors, especially those arising in children, are remarkably heterogeneous in their response to treatment. Understanding the processes that dictate treatment sensitivity is important if we are to cure all patients. Most research has focused on identifying tumor cell intrinsic properties that regulate treatment response; but the role of the tumor microenvironment is less well understood. Here, we show that distinct subtypes of medulloblastoma possess markedly different vasculatures that are determined non-autonomously by tumor genotype, and that dictate response to systemic chemotherapy. We found that WNT-antagonists secreted by WNT-medulloblastoma – an essentially curable form of the disease – silence WNT signaling in neighboring endothelial cells, causing the formation of fenestrated and highly permeable vessels normally associated with peripheral organs: endothelial WNT signaling is essential to form and maintain the blood brain barrier (BBB). Consequently, systemically delivered chemotherapy accumulated to high levels in WNT-medulloblastomas, eliciting a marked clinical response. In contrast, while cells derived from Sonic Hedgehog (SHH)-medulloblastoma – a much less curable subtype – were intrinsically chemosenstive, they did not secrete WNT-antagonists, formed tumors with an intact, chemo-impermeable BBB and were chemoresistant in vivo. Remarkably, reactivation of WNT-signaling in WNT-medulloblastoma endothelial cells restored BBB function, rendering these tumors chemoresistant. Our data provide direct evidence that brain tumor genotype can dictate tumor vessel phenotype in a non-autonomous fashion, providing a potential explanation for the excellent prognosis of WNT-medulloblastoma. Pharmacological inhibition of endothelial WNT signaling in other primary and secondary brain tumors might enhance chemoresponsiveness by disrupting the BBB. Citation Format: Richard J. Gilbertson. Medulloblastoma subgroup-specific mutations model the tumor microenvironment. [abstract]. In: Proceedings of the AACR Special Conference: Advances in Brain Cancer Research; May 27-30, 2015; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2015;75(23 Suppl):Abstract nr IA23.
Barriers to Colorectal Cancer Screening in a Racially Diverse Population Served by a Safety-Net Clinic.

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the US, yet screening rates remain low among minority populations. The purpose of the current study was to identify differences in the endorsement of barriers to CRC screening and to evaluate the association between provider recommendation and CRC screening adherence among Hispanic, Pacific Islander and White patients. This study utilized a cross sectional survey design to identify patient-reported barriers to CRC screening. Logistic regression was utilized to evaluate the association between patient demographic characteristics (race/ethnicity, gender, age), having received provider recommendation, and patient awareness of CRC screening. The study sample was comprised of a diverse population (N = 197); 48% Hispanic, 25% White, 10% Pacific Islander, 4% Black and 13% other races/ethnicity. The median age of participants was 58, yet fewer than 30% were up-to-date for CRC screening. The most commonly cited barriers included fear of test results (27.6%), inability to leave work for a CRC screening appointment (26.9%), being unaware of the need for colonoscopy (25.4%), and lack of provider recommendation for CRC screening (24.9%). Only 16.2% of participants reported that a provider had discussed CRC screening options with them. After adjusting for age and gender, Hispanic patients were less likely to report having had a provider discuss CRC screening options compared to White patients (OR = 0.24, 95% CI: 0.09–0.68, p < 0.05). The findings from this study indicate that patient’s perceived screening barriers, lack of awareness and a lack of provider communication about CRC screening options may contribute to low screening rates among minority populations.
Review: Paradigm and Progeny: Roman Imperial Architecture and Its Legacy, edited by Diane Favro, Fikret K. Yegül, John Pinto, and Guy Métraux

Diane Favro, Fikret K. Yegul, John Pinto, and Guy Metraux, eds. Paradigm and Progeny: Roman Imperial Architecture and Its Legacy Portsmouth, R.I.: Journal of Roman Archaeology, 2015, 228 pp., 12 color and 131 b/w illus. $109, ISBN 9780991373055 While time-honored, Festschriften usually turn out to be a very mixed bag, displaying piety rather than qualitative progress. Paradigm and Progeny is a glorious exception, with every one of its fourteen chapters making a substantive contribution to scholarship on Roman architecture. The book's genesis was a 2011 conference in honor of William MacDonald at the American Academy in Rome that featured a first-rate cast of presenters. That, and the time taken to prepare the papers for publication, has resulted in an excellent volume that constitutes a real tribute to the range of MacDonald's impact on our understanding of Roman architecture and the inspiration he has provided. The chapters have been well edited; there is no prolixity anywhere, and the information and analysis they present on a variety of key subjects will be an important resource for anyone working in the field. The volume is organized into four parts, each reflecting the honoree's interests and legacy. It starts from the ground up with Part 1, “Construction and Design,” with contributions by Gianni Ponti, Marcello Spanu, and Lothar Haselberger. Using the Severan basilica at Lepcis Magna as a test case, Ponti takes up the basic question of coordination between the marble quarry (in this case Proconnesos) and the architects and builders at the final destination. It was a flexible process that allowed “the architect to design and harmonize architectural orders that were quite different both in their structure and their visual impact” (24). This issue also pertains to Haselberger's rich analysis of the components of the Pantheon facade with the help of 3-D laser scanning: the height variances of the columns are well known, and therefore the Corinthian capitals were configured individually in situ so as to compensate for these irregularities, which were not new (as in the Temple of Mars Ultor). …
Comparison of Emergency Department Patients to Inpatients Receiving a Pulmonary Embolism Response Team (PERT) Activation.

Objectives The development of pulmonary embolism response teams (PERTs) has been widely adopted nationally with the goal of providing multidisciplinary care to patients with high-risk PE. Most PERT activations originate from the emergency department (ED), while others are from the intensive care unit (ICU) or inpatient floors. It is unclear if ED PERT activations differ from non-ED PERT activation in terms of presentation, management, and outcome. Methods We enrolled a consecutive cohort of patients for whom PERT was activated at an urban academic medical center. We compared three groups of PERT activations based on whether the activation originated from the ED, ICU, or a non-ICU inpatient floor. We compared these groups in terms of the proportion of PERT activations that occurred during day, evening, or weekend hours and the proportion of confirmed PE. We also compared PE severity, treatment, and outcomes across locations. We tested differences using chi-square tests, with a two-tailed p-value of <0.05 considered statistically significant. Results We enrolled 561 patients, of whom 449 (79.5%) had confirmed PE. The mean ± SD age of patients with confirmed PE was 61 ± 17 years, and 300 (53.5%) were male. Activations from the ED (n = 283, 88.4%) or floor (n = 100, 74.6%) were more likely to be for confirmed PE than activations from the ICU (n = 63, 58.9%; p < 0.0001). There was a statistical difference in the time of day of PERT activation with the ED having more activations during night hours than the ICU or floors (p = 0.004). Most activations for confirmed, massive PE originated from the ICU (n = 41, 65.1%), followed by the ED (n = 82, 29%) and inpatient floors (n = 22, 22%; p < 0.0001). Most activations from the ED (n = 155, 54.8%) and floors (n = 55, 55%) were for submassive PE. The use of thrombolysis or thrombectomy was more common among ICU patients (n = 18, 33.3%), followed by ED patients (n = 53, 19.6%) and then floor patients (n = 8, 8.2%). Mortality and major bleeding events were most common among ICU patients and similar among ED and floor patients. Conclusions Pulmonary embolism response team activations from different clinical locations differ in terms of patient presentation, PE confirmation, treatments, and outcomes. PERTs should be customized to support the different needs of each clinical area.
The Frequency and Severity of Magnetic Resonance Imaging Abnormalities in Infants with Mild Neonatal Encephalopathy

Objective To assess and contrast the incidence and severity of abnormalities on cerebral magnetic resonance imaging (MRI) between infants with mild, moderate, and severe neonatal encephalopathy who received therapeutic hypothermia. Study design This retrospective cohort studied infants with mild, moderate, and severe neonatal encephalopathy who received therapeutic hypothermia at a single tertiary neonatal intensive care unit between 2013 and 2015. Two neuroradiologists masked to the clinical condition evaluated brain MRIs for cerebral injury after therapeutic hypothermia using the Barkovich classification system. Additional abnormalities not included in this classification system were also noted. The rate, pattern, and severity of abnormalities/injury were compared across the grades of neonatal encephalopathy. Results Eighty-nine infants received therapeutic hypothermia and met study criteria, 48 with mild neonatal encephalopathy, 35 with moderate neonatal encephalopathy, and 6 with severe neonatal encephalopathy. Forty-eight infants (54%) had an abnormality on MRI. There was no difference in the rate of overall MRI abnormalities by grade of neonatal encephalopathy (mild neonatal encephalopathy 54%, moderate neonatal encephalopathy 54%, and severe neonatal encephalopathy 50%; P = .89). Basal ganglia/thalamic injury was more common in those with severe neonatal encephalopathy (mild neonatal encephalopathy 4%, moderate neonatal encephalopathy 9%, severe neonatal encephalopathy 34%; P = .03). In contrast, watershed injury did not differ between neonatal encephalopathy grades (mild neonatal encephalopathy 36%, moderate neonatal encephalopathy 32%, severe neonatal encephalopathy 50%; P = .3). Conclusion Mild neonatal encephalopathy is commonly associated with MRI abnormalities after therapeutic hypothermia. The grade of neonatal encephalopathy during the first hours of life may not discriminate adequately between infants with and without cerebral injury noted on MRI after therapeutic hypothermia.
CELLULAR INTERACTION REGULATING EARLY BIOCHEMICAL DIFFERENTIATION IN DICTYOSTELIUM

Summary Accumulation of the developmentally regulated enzyme, N-acetylglucosaminidase, was found to be dependent on conditioning of the buffer by the developing cells of Dictyostelium. Accumulation of three other developmental enzymes, α-mannosidase, threonine deaminase, and tyrosine transaminase, was independent of this conditioning but, for the latter two enzymes, was dependent upon formation of cell clumps. Conditioning of the buffer requires about 12 hrs by cells suspended at 10 7 /ml and does not require concomitant protein synthesis. The substance required for accumulation of N-acetylglucosaminidase appears to be a low molecular weight heat stable molecule secreted both by wild-type and aggregateless cells. The cells respond to the factor by accumulating N-acetylglucosaminidase by a process dependent on concomitant protein and RNA synthesis. The effects of the factor, cell clumping, and encasement of the aggregate in a sheath are discussed in terms of control of the progress along a sequence of dependent stages.
Tendon Tissue Engineering: Mechanism and Effects of Human Tenocyte Coculture With Adipose-Derived Stem Cells

Purpose Adipose-derived stem cells (ASCs) are a potential candidate for cell-based therapy targeting tendon injury; however, their therapeutic benefit relies on their ability to interact with native tenocytes. This study examines the mechanism and effects of coculturing human tenocytes and ASCs. Methods Tenocytes (T) were directly cocultured with either ASCs (A) or fibroblasts (F) (negative control) in the following ratios: 50% T/50% A or F; 25% T/75% A or F; and 75% T/25% A or F. Cells were indirectly cocultured using a transwell insert that allowed for exchange of soluble factors only. Proliferation and collagen I production were measured and compared with monoculture controls. Synergy was quantified using the interaction index (II), which normalizes measured values by the expected values assuming no interaction (no synergy when II = 1). The ability of ASCs to elicit tenocyte migration was examined in vitro using a transwell migration assay and ex vivo using decellularized human flexor tendon explants. Results Compared with monoculture controls, II of proliferation was greater than 1 for all tenocyte and ASC direct coculture ratios, but not for tenocyte and fibroblast direct coculture ratios or for tenocyte and ASC indirect coculture. The ASCs elicited greater tenocyte migration in vitro and ex vivo . The II of collagen I production was greater than 1 for direct coculture groups with 25% T/75% A and 75% T/25% A. Conclusions Direct coculture of ASCs and tenocytes demonstrated synergistic proliferation and collagen I production, and ASCs elicited tenocyte migration in vitro and ex vivo . These interactions play a key role in tendon healing and were absent when ASCs were replaced with fibroblasts, supporting the use of ASCs for cell-based therapy targeting tendon injuries. Clinical relevance When ASCs are delivered for cell-based therapy, they directly interact with native tenocytes to increase cell proliferation, collagen I production, and tenocyte migration, which may enhance tendon healing.
Response by Jadhav et al to Letter Regarding Article, “Interfacility Transfer Directly to the Neuroangiography Suite in Acute Ischemic Stroke Patients Undergoing Thrombectomy”

We thank Lederer et al for their response to our article.1 We agree that increasing lines of evidence now support the importance of fast symptoms onset to recanalization in endovascular therapy with every minute saved translating into more days of extra healthy life. Opportunities to reduce time to recanalization can be considered in the prehospital setting (with triage of appropriate patients directly to endovascular centers), in the referral setting (with efforts to reduce door-in-door-out times) and at the destination hospital. Numerous studies have demonstrated various strategies to reduce hospital arrival to groin access times including minimization of advanced imaging, parallel processing, early activation of the neurocath team, direct transfer to the neurocath laboratory, and minimization of pre- and periprocedural steps …
Review of Small Teaching: Everyday Lessons from the Science of Learning

Political science instructors are busy people, and, despite a desire to offer the highest quality instruction, for many it may not be feasible (or even advisable) to dramatically overhaul their tea...
APPE Evaluations are Positively Associated with MMI, Pre-pharmacy GPA and Pharmacy GPA.

Objective. To determine factors associated with advanced pharmacy practice experience (APPE) performance in the pre-pharmacy and Doctor of Pharmacy (PharmD) curriculum and establish whether performance on the multiple mini interview (MMI) independently predicts APPE evaluation scores. Methods. A multi-case MMI has been used in the admissions process since 2008. Students are scored anywhere from 1 to 7 (unsatisfactory to outstanding) on each interview. Traditional factors (GPA, PCAT, etc.) are also used in the admissions determination. Pearson product-moment correlation and ordinary least squares regression were used to explore the relationships between admissions data, pharmacy GPA, and APPE evaluation scores for the graduating classes of 2011-2014. These analyses identified which factors (pharmacy GPA, PCAT, MMI score, age, gender, rurality, resident status, degree, and underrepresented minority status) related to APPE performance. Results. Students (n=432) had a mean APPE score of 4.6; a mean MMI score of 5.5; mean pharmacy GPA, PCAT and age of 3.14, 73.2, 22.6 years, respectively. Pre-pharmacy GPA and pharmacy GPA positively correlated with mean APPE scores. MMI score demonstrated positive correlations with overall APPE score; including subcategories patient care, documentation, drug information/EBM, public health, and communication. MMI scores were positively related to overall APPE scores in the multivariable regression. Variables showing negative associations with APPE scores included a pre-pharmacy GPA of 3.5) and pharmacy school GPA of >3.0 - 3.5 and GPA 2.6 - 3.0 when compared to GPAs >3.5. Conclusion. GPA (pre-pharmacy and pharmacy) and MMI positively correlate with preceptor-rated performances in the APPE year.
Sediment bacteria in an urban stream: Spatiotemporal patterns in community composition.

Abstract Sediment bacterial communities play a critical role in biogeochemical cycling in lotic ecosystems. Despite their ecological significance, the effects of urban discharge on spatiotemporal distribution of bacterial communities are understudied. In this study, we examined the effect of urban discharge on the spatiotemporal distribution of stream sediment bacteria in a northeast Ohio stream. Water and sediment samples were collected after large storm events (discharge > 100 m) from sites along a highly impacted stream (Tinkers Creek, Cuyahoga River watershed, Ohio, USA) and two reference streams. Although alpha (α) diversity was relatively constant spatially, multivariate analysis of bacterial community 16S rDNA profiles revealed significant spatial and temporal effects on beta (β) diversity and community composition and identified a number of significant correlative abiotic parameters. Clustering of upstream and reference sites from downstream sites of Tinkers Creek combined with the dominant families observed in specific locales suggests that environmentally-induced species sorting had a strong impact on the composition of sediment bacterial communities. Distinct groupings of bacterial families that are often associated with nutrient pollution (i.e., Comamonadaceae, Rhodobacteraceae, and Pirellulaceae) and other contaminants (i.e., Sphingomonadaceae and Phyllobacteriaceae) were more prominent at sites experiencing higher degrees of discharge associated with urbanization. Additionally, there were marked seasonal changes in community composition, with individual taxa exhibiting different seasonal abundance patterns. However, spatiotemporal variation in stream conditions did not affect bacterial community functional profiles. Together, these results suggest that local environmental drivers and niche filtering from discharge events associated with urbanization shape the bacterial community structure. However, dispersal limitations and interactions among other species likely play a role as well.
Metabotypes with elevated protein and lipid catabolism and inflammation precede clinical mastitis in prepartal transition dairy cows

Clinical mastitis (CM), the most prevalent and costly disease in dairy cows, is diagnosed most commonly shortly after calving. Current indicators do not satisfactorily predict CM. This study aimed to develop a robust and comprehensive mass spectrometry-based metabolomic and lipidomic workflow using untargeted ultra-performance liquid chromatography high-resolution mass spectrometry for predictive biomarker detection. Using a nested case-control design, we measured weekly during the prepartal transition period differences in serum metabolites, lipids, inflammation markers, and minerals between clinically healthy Holstein dairy cows diagnosed with mastitis postcalving (CMP; n = 8; CM diagnosis d 1 = 3 cows, d 2 = 2 cows, d 4 = 1 cow; d 25 = 1 cow, and d 43 = 1 cow that had subclinical mastitis since d 3) or not (control; n = 9). The largest fold differences between CMP and control cows during the prepartal transition period were observed for 3'-sialyllactose in serum. Seven metabolites (N-methylethanolamine phosphate, choline, phosphorylcholine, free carnitine, trimethyl lysine, tyrosine, and proline) and 3 metabolite groups (carnitines, AA metabolites, and water-soluble phospholipid metabolites) could correctly classify cows for their future CM status at both 21 and 14 d before calving. Biochemical analysis using lipid and metabolite-specific commercial diagnostic kits supported our mass spectrometry-based omics results and additionally showed elevated inflammatory markers (serum amyloid A and visfatin) in CMP cows. In conclusion, metabolic phenotypes (i.e., metabotype) with elevated protein and lipid metabolism and inflammation may precede CM in prepartal transition dairy cows. The discovered serum metabolites and lipids may assist in predictive diagnostics, prevention strategies, and early treatment intervention against CM, and thereby improve cow health and welfare.
Investigation on the Wetting Behavior of 3C-SiC Surfaces: Theory and Modeling

Silicon carbide (SiC) is a promising material for high-power and high-frequency electronics due to its wide band gap, large breakdown field, and high thermal conductivity. Several applications of micro- and nanoelectronics are found in aqueous environments; thus, it is important to understand the atomic-scale interactions between SiC and water, as these interactions govern the transport processes at solid–liquid interfaces. In an effort to characterize the solid–liquid interactions, the wetting behavior of 3C-SiC was numerically investigated. The wettability of two crystallographic planes ((100) and (111)) was characterized, allowing to have silicon or carbon terminations. It was found that the crystallographic planes as well as the atomic surface terminations play an important role in the wetting behavior of 3C-SiC. Higher hydrophilicity was observed for the Si-terminated surfaces as well as for the SiC(111) crystallographic plane. A combination of a mean-field model of wettability and an analysis of the...
Comparative pharmacokinetics and biodistributions of mebendazole from cosolvent and nanoemulsion formulations in nude athymic mice

2259 Objective: Mebendazole (Mbz), Methyl 5-benzoyl-2-benzimidazole carbamate, exerts growth inhibition in culture and tumor bearing nu/nu mice against NSCLC cell lines. The antineoplastic activity of MBZ is also evident in colorectal carcinoma and melanoma. A nanoemulsion (37 nm) formulation (PM1) of Mbz has been developed in our laboratory for potential parental delivery. This study was to comparatively characterize pharmacokinetics and biodistributions of Mbz from cosolvent formulation and PM1 in nude athymic mice. Method: Mbz was administrated by i.v. bolus to the mice (30-35 gm) at 5 mg/kg for cosolvent system and 2.5 mg/kg for PM1. Concentrations of Mbz in plasma and five organs (heart, lung, liver, spleen, and kidney) were monitored by HPLC assays up to 6 hours post dose. The pharmacokinetic and tissue distribution profiles were constructed and pharmacokinetic parameters were derived using the WinNonlin. Results: The plasma concentration-time profiles of Mbz from cosolvent and PM1 systems followed a two-compartment model with dose normalized AUCs of 2.46 and 2.38 μg·min/ml per μg dose, respectively. The clearance (CL) was 0.41 ml/min for cosolvent and 0.42 ml/min for PM1. The apparent volume distributions at steady-state (Vss) for cosolvent and PM1 were 42.8 ml and 38.8 ml, respectively. Different tissue distribution patterns between the two formulations were observed. For cosolvent, Mbz peak concentrations in different organs were reached in 5 minutes after injection. The highest peak concentration was 76.41 ng/g tissue/μg dose in liver, in contrast to 224.42 ng/g/μg in lung at 2 hr post dose for PM1. Mbz in cosolvent yielded the highest exposure in liver with AUC of 8.24 ug·min/g/ug dose, followed by kidney of 6.67 ug·min/g/ug. However, for PM1, AUC in lung (63.57 ug·min/g/ug) was the highest, which was about 20 folds of that from cosolvent (3.24 ug·min/g/ug), followed by those in liver (5.56 ug·min/g/ug) and kidney (5.22 ug·min/g/ug). For cosolvent, the elimination half-lives were 80, 72, 91, 84 and 98 min in heart, lung, liver, spleen, and kidney, respectively. For PM1, the elimination half-lives were substantially prolonged than those from cosolvent, 96, 172, 193, 123 and 131 min in heart, lung, liver, spleen, and kidney, respectively. Conclusion: Mbz in cosolvent and PM1 systems exhibit similar plasma pharmacokinetics, but distinct tissue distributions. PM1 yields higher Mbz concentrations and prolonged exposures in organs than cosolvent, especially in lung, which may have potential value for lung cancer therapy.
Nonlocal PDF methods for Langevin equations with colored noise

Abstract Langevin equations describe systems subjected to internally generated or externally imposed random excitations. If these excitations correspond to Gaussian white noise, it is relatively straightforward to derive a closed form equation for the joint probability density function (PDF) of state variables. Many natural phenomena present however correlated (colored) excitations. For such problems, a full probabilistic characterization through the resolution of a PDF equation can be obtained through two levels of approximations: first, mixed ensemble moments have to be approximated to lead to a closed system of equations and, second, the resulting nonlocal equations should be at least partially localized to ensure computational efficiency. We propose a new semi-local formulation based on a modified large-eddy diffusivity (LED) approach; the formulation retains most of the accuracy of a fully nonlocal approach while presenting the same order of algorithmic complexity as the standard LED approach. The accuracy of the approach is successfully tested against Monte Carlo simulations.
Niraparib for the treatment of ovarian cancer.

Introduction: Niraparib, an orally available selective inhibitor of poly(adenosine diphosphate-ribose) polymerase (PARP), is the first PARP inhibitor approved for use in patients with ovarian cance...
Scaling up, coverage, and targeting

In this chapter, we examine the current state of knowledge and practice concerned with scaling up and achieving universal coverage of HIV and sexually transmitted diseases (STD) health services, and targeting interventions to specific populations. Recognizing that routes of disease transmission and the consequences of disease cross international borders, the processes of scaling up HIV and STD prevention programs are inherently global issues. Nonetheless, understanding specific local and national contexts is essential to effectively scale up health programs. As illustrated by the emerging research initiatives and resources for program implementation, there is also a push in the USA to build the theory and evidence to improve program performance and scale up programs that contribute to HIV and STD prevention, both nationally and globally. These issues are of importance not only for HIV and STD prevention programs, but they also raise significant political, economic, social, and technical concerns beyond these programs, for many stakeholders at local and national levels. These issues have a prominent place on the global health agenda, and particularly for low and middle-income countries and under-served populations, where HIV and STD prevention have the greatest potential to address the largest burden of disease.
Genetic profiling of medical students.

A medical school project in which students' genetic information is the subject of study raises many ethical questions.
Differential geometry techniques for sets of nonlinear partial differential equations

In Section II of these notes, we will discuss how exterior differential systems geometrically express sets of first order partial differential equations. We emphasize the Cartan integer characters of a system, calculated from the ranks of successive derived sets of homogeneous linear algebraic equations, which show how local integration of generic solutions can proceed. Criteria emerge for the differential system to be well-posed, and for separating coordinates into “independent” and “dependent” variables. Invariant - or coordinate-independent-formulations of associated ordinary differential systems (“Cauchy characteristic” vector fields), internal symmetry groups (“isovectors”), variational principles, etc., can all also be systematically considered.
Fatal motor vehicle traffic accidents among Native Americans.

An atypical number of motor vehicle-related deaths has been observed among Native American populations. Little is known about why Native groups exhibit increased mortality from this cause. To better understand factors influencing these occurrences, I examined fatal motor vehicle traffic accidents between 1980 and 1986 involving persons of Native American descent in New York State, exclusive of New York City. Data were obtained from a review of death certificates and coroner reports. Fatal motor vehicle collisions among Native Americans generally occurred among men (74%), in rural areas (55%), between 9:00 p.m. and 3:00 a.m. (62%), and during weekends (78%). A sizable percentage of motor vehicle deaths resulted from collisions with pedestrians (28%). Death frequently occurred before the accident victim reached a hospital (74%). Median age at death for male victims was eight years greater than for female victims. These data suggest the need for immediate efforts focusing on primary prevention to minimize risk-taking behaviors likely to result in motor vehicle accidents. I discuss behavioral and environmental factors influencing these observations.
Smart Pedagogy: Innovative Teaching and Learning Strategies in Engineering Education

Multiple innovative teaching and learning strategies emerged in the recent years. However, there are no published analysis data and validated outcomes regarding how good those innovative approaches support the main concepts of Smart Education, Smart Classroom and Smart Pedagogy, i.e. their “smartness” levels such as 1) adaptivity, 2) sensing, 3) inferring, 4) anticipation, 5) self-learning, and 6) self-organization. This paper presents the outcomes of the ongoing research, design and development project at the InterLabs Research Institute at Bradley University (IL, U.S.A.) aimed to identify, analyze, test, implement and recommend various components of Smart Pedagogy for Science-Technology-Engineering-Mathematics (STEM) education. The obtained research data and student feedback undoubtedly demonstrate students' keen interest in Smart Pedagogy.
Supervisory Control of Labeled Transition Systems Subject to Multiple Reachability Requirements via Symbolic Model Checking

We present an algorithm to compute the unique maximally permissive state-based supervisor for any deterministic finite labeled transition system subject to a specification with combined invariance and reachability requirements. The specifications that we consider are expressed in computation tree logic and include specifications with multiple reachability requirements, each of which should always be satisfied. The form of the controller (a state-based supervisor) is purely memoryless, so the control decisions can be made by directly sampling the state of the system that is being controlled, without recording any past event or transition history. The algorithm has been implemented in SynthSMV , an extension of the well-known model-checking solver NuSMV, which uses NuSMV’s efficient implementation of symbolic model checking (based on binary decision diagrams). A case study that involves coordinating the operation of a set of reactors in a chemical plant shows how the methods that we develop apply in practice.
TCR-pMHC bond conformation controls TCR ligand discrimination.

A major unanswered question is how a TCR discriminates between foreign and self-peptides presented on the APC surface. Here, we used in situ fluorescence resonance energy transfer (FRET) to measure the distances of single TCR–pMHC bonds and the conformations of individual TCR–CD3ζ receptors at the membranes of live primary T cells. We found that a TCR discriminates between closely related peptides by forming single TCR–pMHC bonds with different conformations, and the most potent pMHC forms the shortest bond. The bond conformation is an intrinsic property that is independent of the binding affinity and kinetics, TCR microcluster formation, and CD4 binding. The bond conformation dictates the degree of CD3ζ dissociation from the inner leaflet of the plasma membrane via a positive calcium signaling feedback loop to precisely control the accessibility of CD3ζ ITAMs for phosphorylation. Our data revealed the mechanism by which a TCR deciphers the structural differences among peptides via the TCR–pMHC bond conformation.
Topological susceptibility in QCD with two flavors and 3-5 colors: A pilot study

I present a calculation of the topological susceptibility ${\ensuremath{\chi}}_{T}$ in $SU({N}_{c})$ gauge theory with ${N}_{c}=3--5$ colors and ${N}_{f}=2$ degenerate flavors of fermions. The results lie on a common curve when expressed in terms of the combination ${N}_{c}{m}_{PS}^{2}{t}_{0}$ where ${m}_{PS}$ is the pseudoscalar meson mass and ${t}_{0}$ is the flow parameter. ${\ensuremath{\chi}}_{T}$ approaches its quenched value as the pseudoscalar mass becomes large. The lattice simulations use clover fermions. They are done at a single lattice spacing, roughly matched across ${N}_{c}$, and over a restricted range of fermion masses.
Comparative Stability Study of Unit-dose Vancomycin Hydrochloride Oral Solutions in Plastic Capped Oral Syringes and Plastic Sealed Dosage Cups.

The objective of this study was to evaluate the stability of vancomycin hydrochloride oral solution prepared using FIRST Vancomycin and FIRVANQ compounding kits, prepared in oral syringes and heat-sealed dosing cups, stored at refrigerated and room temperatures. Triplicate batches of vancomycin hydrochloride oral solution (50 mg/mL) were prepared using FIRST Vancomycin and FIRVANQ kits, aliquoted into plastic oral syringes and sealed dosing cups, stored at refrigerated and room temperatures for a total of eight sample groups. Additionally, remaining samples from FIRVANQ batches were unit-dosed in clear Luer-Lok syringes and stored under refrigeration as a ninth batch. Samples were removed and analyzed for vancomycin recovery using a previously validated high-performance liquid chromatography with ultraviolet detection method over a 30-day period. Recovery was quantitatively assessed by comparing to a freshly prepared United States Pharmacopeia reference standard on each day of sampling. Stability was defined as recovery of 90% to 110% of labeled amount. For all batches and storage conditions tested, the percent recovery of vancomycin remained within the 90% to 110% range throughout the entire 30-day study period. Statistically significant differences based on storage conditions were detected between some test groups, with higher recoveries associated with refrigerated storage. The stability of FIRVANQ is comparable to the solution prepared using the FIRST Vancomycin kit. FIRST Vancomycin and FIRVANQ solutions can be unit dosed, using capped oral syringes or sealed plastic cups, and stored at room temperature or under refrigeration for up to 30 days, which helps improve pharmacy workflow and reduce errors.
Abnormal Kidney Ultrasound in a Transplant Patient with AKI

A 37-year-old man initially presented to an outside emergency department with subjective fever, vomiting, diarrhea, and dysuria. He had ESKD secondary to a posterior urethral valve and reflux nephropathy, for which he had undergone a deceased-donor kidney transplant. On physical examination, the patient was normotensive, tachycardic, and febrile, and he had mild diffuse abdominal tenderness. Laboratory studies showed a serum creatinine level of 2.98 mg/dl (normal range, 0.7–1.3 mg/dl). Both blood and urine cultures grew Escherichia coli . Initial ultrasound was read as moderate to severe hydronephrosis of …
Land Cover Change in a Ghanaian Sacred Forest

Sacred natural sites can be defined as any place in nature possessing a unique spiritual significance to peoples and communities. This chapter examines land cover change in a sacred forest in Ghana to test the hypothesis that designation of a landscape as sacred reduces its forest cover loss over time when compared to neighboring non-sacred forest. Using satellite imagery from 2000, 2012, 2015, and 2017, we generated land cover classification change maps and found that the Goviefe Todzi sacred forest did experience less closed forest loss compared to the surrounding forest area. A visit to the sacred forest in 2018 provided a deeper understanding of the local community’s relationship with the forest and their involvement with preserving the forest through traditional spiritual beliefs.
Escaping Saddle Points with Stochastically Controlled Stochastic Gradient Methods.

Stochastically controlled stochastic gradient (SCSG) methods have been proved to converge efficiently to first-order stationary points which, however, can be saddle points in nonconvex optimization. It has been observed that a stochastic gradient descent (SGD) step introduces anistropic noise around saddle points for deep learning and non-convex half space learning problems, which indicates that SGD satisfies the correlated negative curvature (CNC) condition for these problems. Therefore, we propose to use a separate SGD step to help the SCSG method escape from strict saddle points, resulting in the CNC-SCSG method. The SGD step plays a role similar to noise injection but is more stable. We prove that the resultant algorithm converges to a second-order stationary point with a convergence rate of $\tilde{O}( \epsilon^{-2} log( 1/\epsilon))$ where $\epsilon$ is the pre-specified error tolerance. This convergence rate is independent of the problem dimension, and is faster than that of CNC-SGD. A more general framework is further designed to incorporate the proposed CNC-SCSG into any first-order method for the method to escape saddle points. Simulation studies illustrate that the proposed algorithm can escape saddle points in much fewer epochs than the gradient descent methods perturbed by either noise injection or a SGD step.
Atrial Fibrillation Ablation Using Vein of Marshall Ethanol Infusion

Catheter ablation has become a cornerstone treatment for atrial fibrillation (AF). Pulmonary vein isolation is the accepted approach for paroxysmal AF ablation, but it is less effective for persistent AF. The vein of Marshall (VOM) is located in the epicardial left atrium and can be a source of AF triggers as well as a tract for autonomic nerves. It directly communicates with the underlying myocardium, including the left atrial ridge and the posterior mitral isthmus. This review discusses the latest evidence regarding the mechanisms, procedural aspects, and outcomes of VOM ethanol infusion when used as an adjunct to pulmonary vein isolation in patients with persistent AF.
Comparative species assessments of five-needle pines throughout the western United States

Abstract Five-needle white pine species provide important ecosystem services throughout the western U.S., and many of these species have become susceptible to stressors including warmer temperatures, insect epidemics, nonnative disease, and altered disturbance regimes. The objective of this study was to characterize recent broad-scale demographic patterns, including species abundance (i.e., numbers of individuals, tree density, size-class distributions, recruitment, growth rates, mortality rates, and causes of mortality, for the six species of five-needle pine that occur in the western US. We used the U.S. Forest Service’s Forest Inventory and Analysis (FIA) dataset, spanning greater than 10 years, to quantify demographic status and trends for each species. FIA data were compiled from a probabilistic sample design and consistent analysis framework that included not only the dominant community types of five-needle pines, but also all other forest community types, which have previously been demonstrated to encompass abundant regeneration of five-needle pine species. Our analysis revealed similar trends for whitebark and limber pines: both species exhibited increased levels of mortality that are occurring faster than growth of surviving trees, as well as abundant regeneration in forest types that are not dominated by five-needle pines. Although limber pine has experienced lower mortality rates than whitebark pine, it nonetheless showed signs of decline that are comparable to broad-scale indicators exhibited by whitebark pine 10 years prior. In contrast to whitebark and limber pines, Great Basin bristlecone and foxtail pine mortality rates were relatively low, and their populations exhibited a flat diameter distribution except for restricted recruitment from seedling to sapling size-classes. Our findings suggest that five-needle white pine species would benefit not only from increased seedling recruitment, but also from enhanced recruitment among older and larger age and size classes. Thus, it may be important to apply a variety of management strategies – including artificial regeneration with disease-resistant seedlings, direct seeding, and early intervention to decrease competition that may allow natural regeneration to achieve recruitment inter large size-classes – and also apply silviculture techniques to forest types that may be dominated by other species. The consistent monitoring conducted by FIA can allow future assessment of the demographic trajectory of each five-needle pine species, and thus can help prioritize management and restoration priorities, both within communities dominated by five-needle pines and in other community types that may be important targets for silvicultural interventions or restoration treatments.
Downlink Channel Feedback for FDD Massive MIMO Systems via Tensor Compression and Sampling

In frequency division duplex (FDD) massive MIMO systems, each user equipment (UE) device is required to frequently feed back downlink channel state information to its serving base station (BS), resulting in huge uplink overhead. This paper considers the problem of downlink channel feedback in practical wideband massive MIMO systems operating in the FDD mode. The starting point is to leverage the spatial structure of the BS antenna array to reshape the channel matrix in tensor form, and then bring in orthonormal Tucker (also known as multilinear / higher-order SVD) factorization to approximate the channel tensor on the UE side, and feed the obtained factors back to the BS. The resulting decomposition results in a significant reduction in the number of parameters that needs to be fed back from each UE to its serving BS, without sacrificing channel estimation accuracy. Furthermore, this paper exploits a recently-developed sampling/compression mechanism that efficiently handles the considered problem. Using this approach, each UE is only required to feed back a small number of samples/measurements from the channel tensor, thus shifting the computational burden of tensor decomposition/compression to the BS which naturally possesses higher computational capabilities compared to the UE. Experimental results using channels constructed from a practical ray-tracing simulator demonstrate the superiority of the proposed tensor-based approaches relative to the state-of-the-art.
Current strategies for prevention of oral manifestations of human immunodeficiency virus.

Objectives Strategies to prevent new-onset and recurrent oral manifestations of human immunodeficiency virus (HIV), including fungal, viral, neoplastic, and idiopathic mucosal diseases and destructive periodontal conditions, are poorly understood. Study Design A structured review of the English language literature in PubMed through March 2015 was conducted to identify current prevention strategies for initial and recurrent oral manifestations of HIV. Results Pharmacologic approaches, including combination antiretroviral therapy or other targeted therapies for prevention of oropharyngeal candidiasis, orolabial herpes, oral hairy leukoplakia, oral Kaposi sarcoma, linear gingival erythema and necrotizing ulcerative periodontitis were found. Nonpharmacologic approaches for prevention of oropharyngeal candidiasis, orolabial herpes, oral hairy leukoplakia, and necrotizing ulcerative periodontitis are presented. Conclusions Current strategies for the prevention of oral manifestations of HIV include pharmacologic and nonpharmacologic therapies. Immune reconstitution inflammatory syndrome, future vaccine therapy for pathogens causing oral mucosal disease, and the possible role of oral inflammatory disease prevention in controlling HIV disease progression are discussed.