cssi/SciSciGPT-SciSciNet huggingface dataset:
Looking Through the Judicial Lens: The Implied Covenant of Good Faith and Fair Dealing in Franchise Relationships

It is fair to say that many contract cases involve not just a single transaction between parties, but multiple transactions over an extended period of time. In such instances, the contracting parties often form a relationship that is not easily adjudicated under the most basic principles of contract law and is thereby subject to legal rules, presumptions, and equitable principles — such as the implied covenant of good faith and fair dealing — that are not always present in the express terms of the contract and which are still being developed today. In modern times, a common form of such long-term contractual relationships arises in franchise agreements. As such, this article will critically examine recent developments by the courts of the implied covenant of good faith and fair dealing as applied to the franchise relationship, specifically the continuing debate regarding what principles govern the interpretation of a franchise agreement that is terminated before the contracted end date, and make recommendations as to the application of the implied covenant of good faith and fair dealing to the contractual relationship between franchisors and franchisees. During the 1970s, the franchise relationship came to fruition and, as noted by Professor Hadfield, there was a need for more elasticity in construing the long-term franchise relationship. A dichotomy developed between the franchisors who favored a more strict construction of the franchise agreement and the franchisees who desired more elastic standards of interpreting contractual provisions embodied by the implied covenant of good faith and fair dealing. In examining the court decisions through the date of this article’s publication, it is apparent that neither franchisors nor franchisees get everything they desire in contract interpretation. On one hand, the franchisors have not been able to convince the courts to adopt strict construction of the franchise contracts and, on the other hand, the courts have refused to pronounce a fiduciary relationship between franchisors and franchisees. In describing the tension between two parties to a business transaction that is governed by Article II principles, the authors of the textbook Commercial Transactions: A Systems Approach note, “unfortunately the Article II drafters were better at identifying the tension between freedom of contract and anti-oppression than they were at outlining specific factors to resolve it.” The same observation can be made of regulatory efforts and judicial interpretation of franchise agreements. As Professor Hadfield aptly observed, the elasticity provided by the implied covenant of good faith and fair dealing appears to be a fair standard.
Emerging magnetism and anomalous Hall effect in iridate-manganite heterostructures.

Strong Coulomb repulsion and spin–orbit coupling are known to give rise to exotic physical phenomena in transition metal oxides. Initial attempts to investigate systems, where both of these fundamental interactions are comparably strong, such as 3d and 5d complex oxide superlattices, have revealed properties that only slightly differ from the bulk ones of the constituent materials. Here we observe that the interfacial coupling between the 3d antiferromagnetic insulator SrMnO3 and the 5d paramagnetic metal SrIrO3 is enormously strong, yielding an anomalous Hall response as the result of charge transfer driven interfacial ferromagnetism. These findings show that low dimensional spin–orbit entangled 3d–5d interfaces provide an avenue to uncover technologically relevant physical phenomena unattainable in bulk materials. Whilst superlattices containing thin films of 5d transition metal oxides are expected to yield strong interfacial coupling, only weak effects have been observed. Here, the authors report strong coupling between 3d SrMnO3 and 5d SrIrO3due to the interplay of strong Coulomb and spin orbit interactions.
The contribution of motor vehicle emissions to ambient fine particulate matter public health impacts in New York City: a health burden assessment

On-road vehicles are an important source of fine particulate matter (PM2.5) in cities, but spatially varying traffic emissions and vulnerable populations make it difficult to assess impacts to inform policy and the public. We estimated PM2.5-attributable mortality and morbidity from on-road vehicle generated air pollution in the New York City (NYC) region using high-spatial-resolution emissions estimates, air quality modeling, and local health incidence data to evaluate variations in impacts by vehicle class, neighborhood, and area socioeconomic status. We developed multiple ‘zero-out’ emission scenarios focused on regional and local cars, trucks, and buses in the NYC region. We simulated PM2.5 concentrations using the Community Multi-scale Air Quality Model at a 1-km spatial resolution over NYC and combined modeled estimates with monitored data from 2010 to 2012. We applied health impact functions and local health data to quantify the PM2.5-attributable health burden on NYC residents within 42 city neighborhoods. We estimate that all on-road mobile sources in the NYC region contribute to 320 (95 % Confidence Interval (CI): 220–420) deaths and 870 (95 % CI: 440–1280) hospitalizations and emergency department visits annually within NYC due to PM2.5 exposures, accounting for 5850 (95 % CI: 4020–7620) years of life lost. Trucks and buses within NYC accounted for the largest share of on-road mobile-attributable ambient PM2.5, contributing up to 14.9 % of annual average levels across 1-km grid cells, and were associated with 170 (95 % CI: 110–220) PM2.5-attributable deaths each year. These contributions were not evenly distributed, with high poverty neighborhoods experiencing a larger share of the exposure and health burden than low poverty neighborhoods. Reducing motor vehicle emissions, especially from trucks and buses, could produce significant health benefits and reduce disparities in impacts. Our high-spatial-resolution modeling approach could improve assessment of on-road vehicle health impacts in other cities.
Collision Avoidance and Stabilization for Autonomous Vehicles in Emergency Scenarios

Emergency scenarios may necessitate autonomous vehicle maneuvers up to their handling limits in order to avoid collisions. In these scenarios, vehicle stabilization becomes important to ensure that the vehicle does not lose control. However, stabilization actions may conflict with those necessary for collision avoidance, potentially leading to a collision. This paper presents a new control structure that integrates path tracking, vehicle stabilization, and collision avoidance and mediates among these sometimes conflicting objectives by prioritizing collision avoidance. It can even temporarily violate vehicle stabilization criteria if needed to avoid a collision. The framework is implemented using model predictive and feedback controllers. Incorporating tire nonlinearities into the model allows the controller to use all of the vehicle’s performance capability to meet the objectives. A prediction horizon comprised of variable length time steps integrates the different time scales associated with stabilization and collision avoidance. Experimental data from an autonomous vehicle demonstrate the controller safely driving at the vehicle’s handling limits and avoiding an obstacle suddenly introduced in the middle of a turn.
Comparing inter-organizational new product development strategies: Buy or ally; Supply-chain or non-supply-chain partners?

Abstract Recent supply chain and innovation literature emphasizes the importance of involving external organizations in product development. Building upon this stream of work, this study differentiates four inter-organizational new product development (NPD) strategies based on two dimensions: the external source (supply chain sources [SCS] and non-supply-chain sources [NSCS]) and form of engagement (ally and buy). Using theoretical arguments from the knowledge-based view, we compare the effects of these four strategies on product novelty and product financial performance. Moderated structural equation modeling is used to test the hypotheses, based on survey responses of 267 projects, partially complemented by archival objective data. Results suggest that some strategies are more effective for enhancing product novelty, while others are more beneficial for improving product financial performance. Furthermore, this study reveals no distinction between supply chain and non-supply-chain sources' influences on product novelty. We also show that technology interdependence carries a significant role in enhancing the positive association between product novelty on product financial performance. Overall, this study demonstrates companies need to carefully design their inter-organizational NPD strategies to suit various needs of innovation projects.
Shadow Banking and Regulation in China and Other Developing Countries

The rapid but largely unregulated growth in shadow banking in developing countries such as China can jeopardize financial stability. This article discusses that growth and argues that a regulatory balance is needed to help protect financial stability while preserving shadow banking as an important channel of alternative funding. The article also analyzes how that regulation could be designed.
Chimeric Innexins Reveal Complexities of Electrical Rectification

The innexins ShakingB Lethal (SBL) and ShakingB Neural+16 (SBN16) form heterotypic gap junctions in the Giant Fiber System of Drosophilia melanogaster. The junctions favor arthodromic transmission of action potentials and exhibit properties of rectification when expressed in vivo. Sequence analysis reveals that SBL and SBN16 are similar in size but differ significantly in sequence within the amino terminus (NT), first transmembrane domain (TM1) and first extracellular loop (EL1). It was previously shown that the NT carries properties required for rectification in the sense that homotypic ShakBL junctions can be induced to rectify by replacing the NT of SBL with that of SBN16 in one of the cells. While this result provided a strong first impression about the importance of the NT in rectification, further experiments suggest complex interactions and structural features are required. This is highlighted by the behavior of the reciprocal chimera (SBN16 with the NT of SBL) which does not induce rectification when paired heterotypically with SBN16 but displays voltage-dependent gating similar to SBL when paired homotypically. We previously suggested that the NT but must be paired with an appropriate innexin body in order to induce voltage-dependent rectification and are further investigating features of the innexin channel essential for rectification. We are also investigating the role of various innexin domains in transjunctional (Vj)-dependent gating. Using chimeric constructs that focus on domains with significant sequence variation between SBL and SBN16 (namely NT, TM1 and E1) in combination with Xenopus oocyte expression and electrophysiology we hope to provide insight into the structural determinants of electrical rectification and Vj-dependent gating in innexin-based junctions. The attributes of using splice variants, which are unique to innexin-based gap junctions, will be discussed.
Prospective unbiased experience with three acellular dermal matrices in breast reconstruction

Background The use of acellular dermal matrix (ADM) has become the standard of care in breast reconstruction. However, the majority of current studies are biased or combine large databases introducing inherent flaws. Here, we present a prospective single surgeon experience comparing three ADM. Methods All expander based breast reconstructions between 2014 and 2015 using ADM were included. Results Eighteen patients (32 breasts) underwent reconstruction using Flex Pliable, 15 patients (22 breasts) used Alloderm, and 14 patients (20 breasts) had Dermacell. There were no significant differences in patient demographics or comorbidities. All expanders were placed into a subpectoral position, and there were no direct to implant cases. Average intraoperative fill was comparable, (Flex: 225 cc, Alloderm: 180 cc, Dermacell: 130 cc). There were no differences in seroma, infection, or mastectomy skin flap necrosis rates. There were no cases of red breast, expander explanation or failed reconstruction in any cohort. Time to drain removal was significantly shorter in Flex and Dermacell patients compared to Alloderm (20 days vs 15 days vs 26 days, respectively; P = 0.01). Conclusions While there are differences between available ADM, successful outcomes can be achieved with proper patient selection, sound surgical technique, and diligent post-operative management.
Treatment, short-term outcomes, and costs associated with larynx cancer care in commercially insured patients

Objectives/Hypothesis To examine associations between treatment, complications, and costs in patients with laryngeal cancer. Study Design Retrospective cross-sectional analysis of MarketScan Commercial Claim and Encounters data. Methods We evaluated 10,969 patients diagnosed with laryngeal cancer from 2010 to 2012 using cross-tabulations and multivariate regression. Results Chemoradiation was significantly associated with supraglottic tumors (relative risk ratio [RRR] = 5.9 [4.4–7.8]), pretreatment gastrostomy (RRR = 4.0 [2.7–6.1]), and alcohol abuse (RRR = 0.5 [0.3–0.9]). Treatment-related complications occurred in 23% of patients, with medical complications in 22% and surgical complications in 7%. Chemoradiation (odds ratio [OR] = 3.7 [2.6–5.2]), major surgical procedures (OR = 4.9 [3.5–6.8]), reconstruction (OR = 7.7 (4.1–14.7)], and advanced comorbidity (OR = 9.7 [5.7–16.5] were associated with acute complications. Recurrent/persistent disease occurred in 23% of patients and was associated with high-volume care (OR = 1.4 [1.1–1.8]). Salvage surgery was performed in 46% of patients with recurrent/persistent disease and was less likely for supraglottic disease (OR = 0.5 [0.4–0.8]) and after chemoradiation (OR = 0.4 [0.2–0.6]). Initial treatment and 1-year overall costs for chemoradiation were higher than all other treatment categories, after controlling for all other variables including complications and salvage. High-volume care was associated with significantly lower costs of care for surgical patients but was not associated with differences in costs of care for nonoperative treatment. Conclusions In commercially insured patients <65 years old with laryngeal cancer, chemoradiation was associated with increased costs, an increased likelihood of treatment-related medical complications, and a reduced likelihood of surgical salvage. Higher-volume surgical care was associated with lower initial treatment and 1-year costs of care. These data have implications for discussions of value and quality in an era of healthcare reform. Level of Evidence 2c Laryngoscope, 2017
Gastrointestinal Manifestations of Hereditary Hemorrhagic Telangiectasia (HHT): A Systematic Review of the Literature

Hereditary hemorrhagic telangiectasia (HHT), also called Osler-Weber-Rendu syndrome, is an autosomal dominant genetic disease that affects the vasculature of numerous organs. The prevalence of HHT is estimated to be between 1.5 and 2 persons per 10,000. While there is still much to learn about this condition, there is an increasing understanding its underlying pathophysiology, genetic basis, presentations, and management. Recognizing that the clinical manifestations of HHT can involve a number of organ systems will provide clinicians with a higher index of suspicion for the disease. This early diagnosis and genotyping can greatly reduce mortality for a patient with HHT through appropriate screening for complications. This review will focus on the gastrointestinal manifestations of HHT and how these can dictate treatment and prognosis.
The Ecology of the Colon

The gastrointestinal tract and its contents constitute a dynamic ecosystem, the existence and relative stability of which is very important to the well-being of the host. By definition, ecology of the gut implies the inter- and intraspecific relations among host, microflora, and their environment, with special reference to species distribution and abundance. Interactions within the gastrointestinal tract are numerous and intricate; however, the major interacting components may be considered as: (1) those relating to host physiology, i.e., absorptive and secretory mechanisms and intestinal motility; (2) nutrient supply; and (3) flora.
Making feminist media: third-wave magazines on the cusp of the digital age

In Making Feminist Media, Elizabeth Groeneveld aptly employs textual analysis, editor interviews, and archival research to explore the connections between historical feminist print publications wit...
Acetylsalicylic Acid During Leukapheresis Reduces the Incidence of Clotting in Hematopoietic Progenitor Cell Products.

INTRODUCTION Clots may be seen during hematopoietic progenitor cell (HPC) collection or on product arrival to the cell therapy processing laboratory. We have always given one 81 mg acetylsalicylic acid (ASA) when clotting is seen during collection if there is no allergy, but hypothesized that the incidence of clotting would decrease if ASA was given to all autologous collectors with a platelet count of ≥80×109/L prior to collection (pre-emptively). METHODS Autologous HPC were collected using the Spectra Optia instrument or Cobe Spectra instrument (Terumo BCT®, Lakewood, CO) with heparinized citrate. A retrospective review was performed to determine the total number of HPC products, including products with clots, collected between September 2010 and August 2013 (group 1). All autologous HPC collectors from September 2013 onwards were given ASA pre-emptively if their platelet count was ≥80×109/L (group 2), and a similar review was performed in this group. We included the cell density and platelet count of the HPC products and the platelet count of the patient in the data collected. We reviewed procedure notes for adverse events or bleeding. RESULTS A total of 2574 HPC products were collected between September 2010 and August 2013; clotting was observed in 66 HPC products (66/2574; 2.56%). A total of 1906 HPC products were collected between November 2013 and October 2016; clotting was observed in 24 HPC products (24/1906; 1.25%). Thus an overall reduction was seen in incidence of clotting between groups 1 and 2 (2.56% versus 1.25; P=0.002). Since not all collectors in group 2 received pre-emptive ASA, we reviewed the incidence of clotting within this group. A decrease in incidence of clots was noted with preemptive ASA (group 2A) (5/512, 0.97%) versus no ASA (group 2B) (19/1394, 1.36%), but this was not statistically significant. The mean cell density of the HPC products did not differ significantly between these two groups (group 2A and 2B) but a higher platelet count was observed in the pre-emptive ASA group as expected (group 2A) (P=0.004). Multivariate logistic analysis after adjusting for platelet count of the HPC products showed a trend towards reduced incidence of clotting in the pre-emptive ASA group (group 2A); however no association was seen after adjusting for the cell density of HPC products, nor was an association between patient's platelet count and incidence of clotting seen. None of the collectors who received ASA suffered any adverse events, including bleeding. CONCLUSION We observed an overall reduction in the incidence of clotting in our HPC products after initiating pre-emptive ASA usage (2.56% versus 1.25%; P=0.002). A trend towards lower incidence of clotting was noted when further analysis was performed to include pre-emptive ASA usage and platelet count of the HPC products. Although the overall incidence of clotting was very small (<3.0%), giving ASA pre-emptively further reduced the incidence of clotting and thus prevented wastage/cell loss of HPC products.
DNA Conformation Induces Adaptable Binding by Tandem Zinc Finger Proteins

Tandem zinc finger (ZF) proteins are the largest and most rapidly diverging family of DNA-binding transcription regulators in mammals. ZFP568 represses a transcript of placental-specific insulin like growth factor 2 (Igf2-P0) in mice. ZFP568 binds a 24-base pair sequence-specific element upstream of Igf2-P0 via the eleven-ZF array. Both DNA and protein conformations deviate from the conventional one finger-three bases recognition, with individual ZFs contacting 2, 3, or 4 bases and recognizing thymine on the opposite strand. These interactions arise from a shortened minor groove caused by an AT-rich stretch, suggesting adaptability of ZF arrays to sequence variations. Despite conservation in mammals, mutations at Igf2 and ZFP568 reduce their binding affinity in chimpanzee and humans. Our studies provide important insights into the evolutionary and structural dynamics of ZF-DNA interactions that play a key role in mammalian development and evolution.
Whitebark pine foliar fungal endophyte communities in the southern Cascade Range, USA: Host mycobiomes and white pine blister rust

Abstract We present an assessment of relationships between correlates, signs, and symptoms of white pine blister rust and fungal endophyte communities of whitebark pine (Pinus albicaulis) foliage in the southern Cascade Range, OR, USA. Parsimonious combinations of historically important predictors of blister rust provided effective logistic models (AUC = 0.83) for predicting blister rust infection in whitebark pines at our sites. Holding ten other predictors constant, multivariate endophyte community structure varied significantly with host tree diameter, mountain aspect, the latitudinal coordinates at which samples were collected, and proximal alternative host plants of the white pine blister rust pathogen. After controlling for multiple comparisons, mountain aspect remained a significant source of variation in endophyte community composition even at the taxonomic rank of class, while the presence/absence of blister rust cankers did not remain significant. We discuss overarching mechanisms that may contribute to novel trends observed in mycobiome variation.
"If you do not gamble, check this box": perceptions of gambling behaviors.

Most adults in the U.S. have participated in one or more gambling activities. However, many people engage in gambling activities without considering themselves as gamblers. Four hundred and forty-nine university students returned surveys about their participation in gambling activities. After completing a questionnaire recording the style and frequency of gambling participated in, respondents were asked to indicate whether or not they gambled. Results indicated that gamblers participated in twice as many forms of gambling activities as those who classified themselves as non-gamblers. Scratch tickets and lottery tickets were not generally considered gambling unless purchased frequently. Casino visits, bingo, dog races, football pools, golf matches, local poker games, and other card games were more likely to be viewed as gambling, especially when engaged in frequently. Subjects who had gambled on at least one occasion with bookies, dice games, video poker in a bar, dog or cock fights, or off track betting almost always identified themselves as gamblers. It is recommended that further research be conducted to clarify the gambling activities, and frequency of those activities, that influence a person's perceptions of gambling.
ICONCHESS: an Interactive CONsultant for CHESS middlegames

Ever since Shannon [Shannon 50] published his proposal for a chess playing program, most programs have followed the brute force approach to chess, which relies on searching a large number of possible chess positions in order to produce a move that is appropriate for a given chess position. Programs that have dominated the computer chess scene through the years, such as those described in [Marsland et al. 90], rely primarily on fast search-based algorithms and/or special purpose chess hardware rather than on an intensive application of knowledge. A few systems have used a knowledge-based approach to deal with chess positions. Unfortunately, these programs [Wilkins 80], [Pitrat 77] have been able to deal only with very limited subsets of the game. The problem of teaching chess has also been rarely explored. In addition to the canned tutorials found with several commercial chess programs, the intelligent tutoring system UMRAO [Gadwal 90], and the Chessmaster's natural language advisor, while limited, are perhaps the most representative examples of the application of artificial intelligence (AI) techniques for teaching chess. Despite the limited effort in this direction, cognitive psychology research suggests the importance of different factors, such as inexact pattern recognition [De Groot 78], [Newell et al. 72], and high-level knowledge [Cooke et al. 93] which have been successfully handled by AI techniques, such as case-based reasoning (CBR) [Schank 89], and fuzzy logic in the creation of learning environments in other fields, [Schank et al. 94], [Edelson 92], [McNeill et al. 94]. ICONCHESS combines some of these techniques in a learning environment for chess middlegames.
Stretching the Paradigm or Building a New? Development of a Cohesive Language for Vibrational Communication

Before we can recruit the broader community to share our conviction of substrate-borne communication in animals as ancient, important, widely employed in vertebrates, and perhaps exclusively employed in a broad range of arthropod taxa, we first must assess our current status within the animal communication paradigm and plot a course with that focused goal in sight. We must agree on the words we use to unambiguously communicate research findings among ourselves. We can do this rapidly through consensus, or allow terminology and protocols to slowly evolve to cohesion over an extended period of time through inaction. This chapter briefly explores the current position of shared core concepts on vibrational communication within the framework of Thomas Kuhn’s Structure of Scientific Revolutions and suggests that the study of substrate-borne vibrational communication really can be accommodated within the dominant paradigm of animal communication. We require a reinterpretation of what ‘everyone knows to be true’ in some cases where empirical studies now have falsified previous widely held assumptions. A first step might be to develop a concerted, coordinated strategy that is widely employed by those currently studying vibrational communication. The paradigm can be stretched without being replaced, or we can forge a separate paradigm for vibrational communication. It is simply time to collectively decide on a course of action.
THE DESIGN OF A MYOELECTRICALLY CONTROLLED UPPER ARM PROSTHESIS WITH VARIABLE MECHANICAL IMPEDANCE

Recent neurophysiological research has demonstrated that an important aspect of movement control is the variability of mechanical parameters of the musculo-skeletal system. By co-activation of antagonist muscles such as the biceps and triceps, the individual can adjust the damping and the stiffness about the joint. The design of a myoelectrically controlled upper arm prosthesis with a high fidelity feedforward control path is presented. As with the natural arm, this device gives the user capability of tuning the mechanical impedance about the elbow joint to the task at hand. Variation of the stiffness and damping is accomplished through the variation of the gains in feedback loops within the arm itself. Parasitic impedances in the drive train (i.e. energy storages and non-linearities) are minimized so as to enhance the controllability of the prosthesis.
Symplectomorphism Groups and Quantum Cohomology

We discuss the question of what quantum methods (J-holomorphic curves and quantum homology) can tell us about the symplectomorphism group and its compact subgroups. After describing the rather complete information we now have about the case of the product of two 2-spheres, we describe some recent results of McDuff-Tolman concerning the symplectomorphism group of toric manifolds. This leads to an interpretation of the relations in the quantum cohomology ring of a symplectic toric manifold in terms of the Seidel elements of the generating circles of the torus action.
Staphylococcal coagglutination for the detection of the enterotoxin of Clostridium perfringens

The staphylococcal coagglutination technique has been used in recent years for detecting various bacterial antigens and toxins. It is a simple and rapid technique which requires no specialized equipment. This report describes a staphylococcal coagglutination procedure for assaying C. perfringens enterotoxin. Its sensitivity and specificity were studied with the aid of various enterotoxin preparations and culture filtrates of C. perfringens and other Clostridium species. This assay detects between 1.9 and 3.8 micrograms of enterotoxin per ml. Only the enterotoxin preparations and the C. perfringens culture fluids were positive.
Translating Critical Design: Agonism in Engineering Education

Speculative and Critical Design (SCD) methods can produce provocative artifacts that help audiences recognize the political worlds in which all designed objects participate. Similarly, SCD can be l...
Artificial Intelligence and the Future of Primary Care: Exploratory Qualitative Study of UK General Practitioners' Views.

Background: The potential for machine learning to disrupt the medical profession is the subject of ongoing debate within biomedical informatics and related fields. Objective: This study aimed to explore general practitioners’ (GPs’) opinions about the potential impact of future technology on key tasks in primary care. Methods: In June 2018, we conducted a Web-based survey of 720 UK GPs’ opinions about the likelihood of future technology to fully replace GPs in performing 6 key primary care tasks, and, if respondents considered replacement for a particular task likely, to estimate how soon the technological capacity might emerge. This study involved qualitative descriptive analysis of written responses (“comments”) to an open-ended question in the survey. Results: Comments were classified into 3 major categories in relation to primary care: (1) limitations of future technology, (2) potential benefits of future technology, and (3) social and ethical concerns. Perceived limitations included the beliefs that communication and empathy are exclusively human competencies; many GPs also considered clinical reasoning and the ability to provide value-based care as necessitating physicians’ judgments. Perceived benefits of technology included expectations about improved efficiencies, in particular with respect to the reduction of administrative burdens on physicians. Social and ethical concerns encompassed multiple, divergent themes including the need to train more doctors to overcome workforce shortfalls and misgivings about the acceptability of future technology to patients. However, some GPs believed that the failure to adopt technological innovations could incur harms to both patients and physicians. Conclusions: This study presents timely information on physicians’ views about the scope of artificial intelligence (AI) in primary care. Overwhelmingly, GPs considered the potential of AI to be limited. These views differ from the predictions of biomedical informaticians. More extensive, stand-alone qualitative work would provide a more in-depth understanding of GPs’ views.
A phase I clinical trial of prolonged infusion of hydroxyurea in combination with hyperfractionated, accelerated, external radiation therapy in patients with advanced squamous cell cancer of the head and neck.

Background: Preclinical data suggested that sustained inhibition of the anabolic enzyme, ribonucleotide reductase (RR), by hydroxyurea (HU) may be critical for the anticancer effects of the drug. A phase I trial of continuous infusion HU with concomitant hyperfractionated, accelerated radiation therapy (CHU-CHRT) was initiated to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of HU in patients with locally advanced squamous cell carcinoma (SCC) of the head and neck. Methods: Patients were required to have histologically-documented and radiographically-staged locally advanced SCC of the hypopharynx (AJC stages II, III or IV), oropharynx (AJC stage IV), or oral cavity (AJC stage IV) not amenable to reasonable surgical resection. Eligible patients had adequate bone marrow, hepatic, and renal function and had to give informed consent. Concomitant, hyperfractionated, accelerated radiation therapy (CHRT) consisted of 1.2 Gy BID (6 hour minimum interfraction interval) on weekdays and 1.2 Gy delivered daily on the weekends to a total tumor dose of 74.4 Gy. Continuous infusion hydroxyurea (CHU) was administered at 0.25–0.375 mg/m2/min as a continuous intravenous infusion daily for 5 days with weekends days off for the duration of the radiation therapy. The dose of HU was increased by 0.125 mg/m2/min between dose levels until DLT was reached in 2/6 patients. If the primary had a complete clinical response and biopsies were negative, planned neck dissections were performed. Results: Fifteen patients were enrolled and are evaluable. The initial dose level, 0.25 mg/m2/min was tolerated by 3/3 patients. At 0.375 mg/m2/min, 3/6 patients experienced grade 3–4 infections, with one patient having a non-fatal, subendocardial infarction. At 0.313 mg/m2/min, no patient experienced DLT. Conclusion: The MTD for CHU-CHRT was 0.313 mg/m2/min. The toxicities were primarily mucosal and a phase II study is in progress.
On the verge of Umdeutung in Minnesota: Van Vleck and the correspondence principle (Part One)

This is the second installment of a two-part paper on developments in quantum dispersion theory leading up to Heisenberg's "Umdeutung" paper. In telling this story, we have taken a paper by John H. Van Vleck as our main guide. In this second part we present the detailed derivations on which our narrative in the first part rests. The central result that we shall derive is the Kramers dispersion formula, which played a key role in the thinking that led to Heisenberg's "Umdeutung" paper. Closely following Van Vleck's pre-Umdeutung approach, we derive classical and construct quantum formulae for the dispersion, emission, and absorption of radiation both for the special case of a charged harmonic oscillator (sec. 5) and for arbitrary non-degenerate multiply-periodic systems (sec. 6). In sec. 7, we rederive the same results using modern quantum mechanics. In sec. 8 we bring together the main conclusions of our study.
Performance of muscadine grape cultivars in southern Georgia.

1 Department of Horticulture, University of Georgia-Tifton Campus, 4604 Research Way, Tifton, GA 31793. E-mail: pconner@uga.edu. Abstract A trial of 31 muscadine grape cultivars was evaluated in southern Georgia, USA, from 2004 through 2008. The vineyard was planted in 2000 and expanded in 2006. Vines were evaluated for vigor, leaf and fruit disease, harvest period, ripening uniformity, pedicel scar, and visual estimation of crop load. In 2007 and 2008 berry weight, berry diameter, and percent soluble solids was measured on a subset of the cultivars. Based on these data, ‘Early Fry’, ‘Fry’, ‘Summit’ and ‘Supreme’ are recommended as main cultivars for the commercial fresh fruit market in Georgia. ‘Triumph’, ‘Tara’, and ‘Granny Val’ are recommended as commercial market pollinizers. Additionally ‘Nesbitt’ and ‘Cowart’ are recommended as pick-your-own pollinizers. ‘Noble’ is recommended as a black juice grape, and growers are encouraged to try ‘Doreen’ and ‘Welder’ as replacements for ‘Carlos’ as bronze juice grapes with better fruit rot resistance.
Protective effect of phosphatidylserine blockade in sepsis induced organ dysfunction.

Abstract Background Phosphatidylserine is usually an intracellularly oriented cell membrane phospholipid. Externalized phosphatidylserine on activated cells is a signal for phagocytosis. In sepsis, persistent phosphatidylserine exposure is also a signal for activation of the coagulation and inflammatory cascades. As such, phosphatidylserine may be a key molecule in sepsis induced cellular and organ injury. We hypothesize that phosphatidylserine blockade provides a protective effect in sepsis induced organ dysfunction. Methods Sepsis was induced in adult female rats using an endotoxin model. Diannexin, a homodimer of annexin A5, was administered for phosphatidylserine blockade. Rats were allocated to control ( n = 5), sepsis ( n = 6), or sepsis and phosphatidylserine blockade ( n = 9) groups. Gut, pulmonary, renal, and hematologic dysfunctions were evaluated by mesenteric microvascular fluid leak, partial pressure of oxygen, serum creatinine, activated clotting time, and glomerular fibrin deposition, respectively. Results Rats in the sepsis group demonstrated gut, renal, and hematologic dysfunction. Phosphatidylserine blockade reversed signs of gut dysfunction and mesenteric microvascular leak ( P 01). In addition, phosphatidylserine blockade corrected systemic coagulopathy, as measured by activated clotting time ( P = . 03) and glomerular fibrin deposition ( P = . 008). There was no difference in renal dysfunction ( P = . 1) or pulmonary dysfunction in any of the groups ( P = . 6). Conclusion In sepsis, phosphatidylserine blockade had a protective effect on gut dysfunction and coagulopathy. Increased phosphatidylserine exposure may be a key mediator of organ dysfunction and coagulopathy during sepsis. These data may provide insights into novel treatment options for septic patients.
Therapeutics for Inflammatory Bowel Diseases in Children and Adolescents: A Focus on Biologics and an Individualized Treatment Paradigm.

Pharmacologic treatment of children and adolescents with inflammatory bowel diseases (IBD) [Crohn’s disease and ulcerative colitis] requires consideration of disease and medication effects on growth and nutrition, the importance of durability of biologics, and concerns for long-term sequelae of disease and therapies. Achieving early remission in children with Crohn’s disease correlates with improved outcomes and therefore allows a window of opportunity for maximizing growth. Thus, there is a great need to treat children and adolescents with the right drug at the right time while achieving adequate exposure. Improved understanding of disease phenotypes, disease natural history, and risk stratification will play a critical role in treatment selection for children, particularly as more therapeutic options become available. Here we summarize data supporting newer concepts of treating the individual child with IBD through targeted early biologic treatment, including utilization of therapeutic drug monitoring to optimize treatment effects and the use of early antitumor necrosis factor (TNF)-α therapies to mitigate long-term sequelae of the disease. Recent inception cohort studies provide important data regarding the risk stratification of children and adolescents with IBD, which support a move toward a personalized therapeutic approach to IBD in children and adolescents.
Neural responses to monetary incentives in bipolar disorder

Although behavioral sensitivity to reward predicts the onset and course of mania in bipolar disorder, the evidence for neural abnormalities in reward processing in bipolar disorder is mixed. To probe neural responsiveness to anticipated and received rewards in the context of bipolar disorder, we scanned individuals with remitted bipolar I disorder (n = 24) and well-matched controls (n = 24; matched for age and gender) using Functional Magnetic Resonance Imaging (FMRI) during a Monetary Incentive Delay (MID) task. Relative to controls, the bipolar group showed reduced NAcc activity during anticipation of gains. Across groups, this blunting correlated with individual differences in impulsive responses to positive emotions (Positive Urgency), which statistically accounted for the association of blunted NAcc activity with bipolar diagnosis. These results suggest that blunted NAcc responses during gain anticipation in the context of bipolar disorder may reflect individual differences in Positive Urgency. These findings may help resolve discrepancies in the literature on neural responses to reward in bipolar disorder, and clarify the relationship between brain activity and the propensity to experience manic episodes.
Chronic oral toxicity studies of the angiogenesis inhibitor, ammonium tetrathiomolybdate

4097 Chronic (6-month and 9-month) oral toxicity studies were conducted in rats and dogs to characterize the toxicity of ammonium tetrathiomolybdate (ATTM), an angiogenesis inhibitor being developed as a cancer therapeutic. In addition to toxicology, clinical pathology, and histopathology endpoints, study designs assessed the utility of copper supplementation in the prevention of ATTM toxicity, and evaluated plasma ceruloplasmin as a possible biomarker of ATTM action. In rats, chronic gavage administration of ATTM at doses of 0.25, 1.0, or 4.0 mg/kg/day did not induce mortality, alterations in body weight, or gross toxicity. No evidence of drug-related ocular toxicity, neurotoxicity, or immunotoxicity was identified in any study animal, and micronucleus evaluations were negative. Effects on hematology, clinical chemistry, and tissue morphology were seen only in rats receiving the high dose of ATTM, and included minimal to mild anemia, modest alterations in several clinical pathology parameters, hepatomegaly, and microscopic alterations in the tibia and epididymis. Anemia, hepatomegaly, most clinical pathology alterations, and most microscopic changes were partially or completely prevented by co-administration of copper; all effects other than sperm granulomas in the epididymis were reversed upon discontinuation of ATTM exposure. In dogs, administration of ATTM at doses of 0.3, 1.0, or 3.0 mg/kg/day for 9 months induced no effects on any toxicologic parameter examined except for microscopic alterations in the liver (1.0 and 3.0 mg/kg/day doses only). Microscopic alterations in dogs treated with ATTM were not reduced by co-administration of copper, and were not reversed upon discontinuation of exposure. In rats, plasma ceruloplasmin was reduced in dose-related fashion by ATTM; this reduction was ameliorated by copper supplementation, suggesting that ceruloplasmin is a useful biomarker of ATTM action in rats. By contrast, baseline levels of ceruloplasmin in dogs were very low, and were not reproducibly altered by ATTM. The No Observed Adverse Effect Level for chronic administration of ATTM was 1.0 mg/kg/day (6 mg/m2/day) in rats and 0.3 mg/kg/day (6 mg/m2/day) in dogs. (N01-CM-85102 from the NCI.)
Plant regeneration of red raspberry ( Rubus idaeus ) cultivars ‘Joan J’ and ‘Polana’

Plants were regenerated from in vitro leaf and petiole tissues of Rubus spp. L. (red raspberry) ‘Joan J’ and ‘Polana’ in woody plant medium (WPM), with 200 mg L−1 polyvinylpyrrolidone (PVP), and various combinations of 6-benzylaminopurine (BA) and/or thidiazuron (TDZ). The effects of explant type and explant age on plant regeneration were also investigated. Results showed that the regeneration rates were 70% for ‘Joan J’ and 82.2% for ‘Polana,’ when 7-d-old leaf tissues were inoculated on WPM with 2.5 μM BA + 1.0 μM TDZ and WPM with 2.5 μM BA + 0.1 μM TDZ, respectively. For ‘Joan J,’ in vitro rooting was readily achieved (100%) in one-half Murashige and Skoog (MS) medium supplemented with 10 μM 1-naphthaleneacetic acid (NAA). For ‘Polana,’ a rooting rate of 75% was achieved when cuttings were pulsed in one-half MS with 20 μM NAA for 7 d and then transferred to auxin-free one-half MS medium. An efficient ex vitro rooting frequency (> 80%) was obtained for both cultivars when cuttings were quickly dipped in 500 μM Indole-3-burytic acid (IBA) or NAA, and inserted to Sunshine Mix no. 1 (Fisons Western Corp., Vancouver, Canada) for a 4-wk rooting and acclimatization period. Regenerated plants were eventually grown in the greenhouse. This research will assist germplasm improvement using biotechnology techniques for raspberries and other Rubus species.
Genome-wide molecular effects of the neuropsychiatric 16p11 CNVs in an iPSC-to-iN neuronal model

Copy number variants (CNVs), either deletions or duplications, at the 16p11.2 locus in the human genome are known to increase the risk for autism spectrum disorders (ASD), schizophrenia, and for several other developmental conditions. Here, we investigate the global effects on gene expression and DNA methylation using a 16p11.2 CNV patient-derived induced pluripotent stem cell (iPSC) to induced neuron (iN) cell model system. This approach revealed genome-wide and cell-type specific alterations to both gene expression and DNA methylation patterns and also yielded specific leads on genes potentially contributing to some of the known 16p11.2 patient phenotypes. PCSK9 is identified as a possible contributing factor to the symptoms seen in carriers of the 16p11.2 CNVs. The protocadherin (PCDH) gene family is found to have altered DNA methylation patterns in the CNV patient samples. The iPSC lines used for this study are available through a repository as a resource for research into the molecular etiology of the clinical phenotypes of 16p11.2 CNVs and into that of neuropsychiatric and neurodevelopmental disorders in general.
An Empirical Examination of the Term Structure Fundamentals of Credit Spreads

Using an exponential model of jumps to default, this research investigates the fundamentals that determine the spreads required by investors for corporate credit risk at different maturities. The empirical results indicate that CDS prices across the term spectrum are strongly associated with interrelated probabilities of cash, income, and valuation insolvency, as well as with market-based measures of systematic risk. Although the financial functions best fitting CDS prices are found to vary somewhat by maturity, an integrated model with constant parameters across time, company, and term is found to explain about 50% of individual credit spreads both in sample and ex-post. TOPICS:Credit risk management, credit default swaps Key Findings • Using nonnegative least squares procedures to find the structural model forms which best fit credit spreads across the term structure, this empirical research explains over half of individual CDS prices in and out of sample. • CDS prices with shorter terms (like 1–3 years) are found to be most strongly determined by the probability of a company generating negative income and running out of cash, but the likelihood of cash and income insolvency is discovered to also have important impacts at longer maturities of 5–10 years. • The 378,401 individual credit spreads in the sample over the 2008–2019 interval are found to incorporate time-varying systematic risk premiums (estimated from market prices), as well as reflect the integrated risks of income, cash, and valuation insolvency on any day.
Developing a Finite Geometry: A Math Club Approach.

HIGH SCHOOL students who have had successful experience with elementary algebra, naive set theory, plane geometry, and mathematical systems form the au dience for whom this paper was written. It is hoped, however, that others, too, will find it appropriate and enjoyable. It provides an example of a finite geometry; the axioms for a nine-point geometry are presented and used to prove ten theorems in a mathematically sound development. It illustrates the use of intuition (particu larly sketches) in developing a rigorous proof. It strengthens the concept of math ematical system; to solve a complicated problem, the students in the story develop a mathematical system that describes the problem situation. Readers will undoubt edly discover other uses.