cssi/SciSciGPT-SciSciNet huggingface dataset:
Activation of rostral ventromedial medulla neurons by noxious stimulation of cutaneous and deep craniofacial tissues

The rostral ventromedial medulla (RVM) projects to the medullary and spinal dorsal horns and is a major source of descending modulation of nociceptive transmission. Traditionally, neurons in the RVM are classified functionally as ON, OFF, and NEUTRAL cells on the basis of responses to noxious cutaneous stimulation of the tail or hind paw. ON cells facilitate nociceptive transmission, OFF cells are inhibitory, whereas NEUTRAL cells are unresponsive to noxious stimuli and their role in pain modulation is unclear. Classification of RVM neurons with respect to stimulation of craniofacial tissues is not well defined. In isoflurane-anesthetized male rats, RVM neurons first were classified as ON (25.5%), OFF (25.5%), or NEUTRAL (49%) cells by noxious pinch applied to the hind paw. Pinching the skin overlying the temporomandibular joint (TMJ) altered the proportions of ON (39.2%), OFF (42.2%), and NEUTRAL (19.6%) cells. To assess the response of RVM cells to specialized craniofacial inputs, adenosine triphosphate (ATP; 0.01–1 mM) was injected into the TMJ and capsaicin (0.1%) was applied to the ocular surface. TMJ and ocular surface stimulation also resulted in a reduced proportion of NEUTRAL cells compared with hind paw pinch. Dose-effect analyses revealed that ON and OFF cells encoded the intra-TMJ concentration of ATP. These results suggest that somatotopy plays a significant role in the functional classification of RVM cells and support the notion that NEUTRAL cells likely are subgroups of ON and OFF cells. It is suggested that a portion of RVM neurons serve different functions in modulating craniofacial and spinal pain conditions.
Seeking Justice: Citizens' Use of Fair Hearings to Correct Errors in Public Welfare Bureaucracies

An understudied area of public administration is administrative hearings, used by clients to challenge denials or reductions of aid in public welfare programs. They help ensure that officials are applying the law consistently, fairly and equitably, and as intended by policy makers. Drawing on 59 qualitative interviews with public assistance clients in an urban and suburban county in New York who received notices discontinuing or reducing their assistance, this study explores why clients appeal or not and their perceptions of hearings. The findings indicate that clients’ decisions to contest agency decisions were influenced by their perceptions of how workers treated them, their reactions to powerlessness and stigma, and their social networks, especially client networks. Clients who filed appeals perceived hearings as a valuable tool, albeit one that needed improvements. Although concerned with outcomes, they also focused on the procedural fairness of the hearing and whether they had an opportunity to fully present their case to an impartial decision maker. Although some clients had difficulty navigating the appeals process, procedural fairness was possible to achieve, despite the evident power and status disparities between the parties.
Disruption of Decrements in Conditioned Stimulus Processing by Selective Removal of Hippocampal Cholinergic Input

The attention directed to environmental stimuli can be modified by experience. For example, preexposure of a conditioned stimulus (CS) in the absence of reinforcement can retard subsequent conditioning of that stimulus when it is paired directly with an unconditioned stimulus, a phenomenon referred to as latent inhibition. Similarly, consistent pairings of a CS with another event can slow the acquisition of new information about that CS. Such phenomena suggest that reductions in the processing of CSs occur when they are made behaviorally irrelevant or consistent predictors of other events. On the basis of the observation that hippocampal lesions prevented such reductions in CS processing, we hypothesized that damage to basal forebrain cholinergic neurons that project to the hippocampus, using microinjections of the selective immunotoxin 192 IgG-saporin into the medial septum/vertical limb of the diagonal band (MS/VDB), also would disrupt normal reductions in CS processing. Lesions of hippocampal cholinergic input disrupted decreases in CS processing, manifested in both an absence of latent inhibition and a lack of reduced processing of a CS that had been a consistent predictor of another CS. These results indicate that cholinergic neurons in the MS/VDB play a role in the regulation of CS processing. Furthermore, these findings (in conjunction with previous findings) implicate both rostral (hippocampal-projecting) and caudal (cortical-projecting) regions of the basal forebrain cholinergic system in the modulation of attention.
GATS and water services: the implications for low-income households in the South

This paper considers the implications of the General Agreement on Trade in Services for the delivery of water to low-income residential customers in the South. The specific feature of the GATS is the liberalization of water supplies. The paper argues that the GATS may, depending on national government commitments, limit the ways in which the water market can be developed and structured by the state. With a focus on the implications for access for the poorest, the discussion explores three possible ways in which the GATS may constrain the capacity of local agencies (state and civil society) to extend the supply of clean water to those most in need.
Conservative Shape-Preserving Two-Dimensional Transport on a Spherical Reduced Grid

Abstract A new discretization of the transport equation for two-dimensional transport is introduced. The scheme is two time level, shape preserving, and solves the transport equation in flux form. It uses an upwind-biased stencil of points. To ameliorate the very restrictive constraint on the length of the time step appearing with a regular (equiangular) grid near the pole (generated by the Courant-Friedrichs-Lewy restriction), the scheme is generalized to work on a reduced grid. Application on the reduced grid allows a much longer time step to be used. The method is applied to the test of advection of a coherent structure by solid body rotation on the sphere over the poles. The scheme is shown to be as accurate as current semi-Lagrangian algorithms and is inherently conservative. Tests that use operator splitting in its simplest form (where the 2D transport operator is approximated by applying a sequence of 1D operators for a nondivergent flow field) reveal large errors compared to the proposed unsplit s...
Assessing The Descriptive Accuracy of Three Theories of Long-Term Profitability For a Service Industry

The interrelationships of size, market strategy, and profitability were investigated for the cable network industry. Roach’s size-profitability relationship was found. The observed strategy profitability relationship supports the profitability of Porter’s cost leadership strategy and suggests that successful implementation is a stipulation for the efficacy of his focus strategy.
Invention and Innovation in African Iron-smelting Technologies

Sub-Saharan Africa is often characterized by Europeans as a region that saw no significant technological change from the adoptions of agriculture and ironworking until the European colonization of the entire continent after 1880. This article criticizes this view by exploring the distinction between invention and innovation, using African iron smelting as a case study. It argues that there is in fact much evidence for the invention of new technologies in recent African prehistory, but that very low population densities precluded innovations in mass production and transportation.
Potential Mechanisms of PTA: Cell Death

Post-traumatic osteoarthritis is the development of secondary osteoarthritis after severe traumatic joint injury, especially one that involves an intra-articular fracture. The initial acute injury causes structural damage to the matrix of articular cartilage, which is accompanied by cellular responses ranging from the upregulation of matrix degradative and synthetic pathways, activation, release of oxidants and inflammatory cytokines, and cell death. In the chronic phase, residual alterations in joint biomechanics such as instability secondary to chronic joint laxity (following ligament rupture) or abnormality in articular surface geometry (such as malreduction associated with intra-articular fractures) compound the initial injury and can lead to ongoing matrix degradation with concomitant cell death. This chapter contrasts the various types of cell death that have been documented after mechanical injury, reviews the potential mechanisms and pathways leading to post-traumatic cell death, discusses possibilities for therapy to prevent cell death as a means of reducing ongoing degeneration, and suggests directions for future research that are necessary to advance our understanding of cellular death and the relevant therapeutic implications.
Security management of enterprise' LAN

The paper analyzed problems existing in security management in LAN,including hacker attack,IP embezzled,system vulnerability and data' security in database,and proposed countermeasures.
Relationship between Genotypes and Mutation of Hepatitis B Virus in 88 Hepatitis B Patients in Shanghai

[Objective]To understand the distribution of genotypes and mutation of hepatitis B virus(HBV) in hepatitis B patients.[Methods]Eighty-eight hepatitis B patients in Shanghai were randomly sampled in 2010.Nested polymerase chain reaction(PCR) was carried out to detect genotypes of HBV in blood samples of the selected patients.The pre-S/S and C gene regions of HBV DNA were amplified and sequenced.[Results]Among the 88 subjects,52 patients(59.09%) were infected by HBV genotype C and 36 patients(40.91%) by HBV genotype B.The mean age of HBV genotype B group[(38.56±12.55) years old]was lower than that of HBV genotype C group[(44.54±15.72) years old]with significantly statistical difference(P0.05).The positive rate of hepatitis B e antigen(HBeAg) in the HBV genotype B group(66.67%) was significantly higher than that of the HBV genotype C group(28.85%)(P0.05).The mutation rates of C1762 and C1764 situs in HBV genotype C group were 50% and 50.77% respectively,statistically higher than those of the genotype B group which were 27.78% and 25% respectively(P0.05).[Conclusion]The hepatitis B patients in this study are dominantly infected with genotype C.The mutation rates of C1762 and C1764 situs in patients with genotype C were higher than those with genotype B.Strengthened surveillance on genotype and mutation of HBV is required.
Particular solutions of some elliptic partial differential equations via recursive formulas

Using the principle of the method of undetermined coefficients and the technique of upper triangular systems of linear algebraic equations,a simple and direct iterative numerical procedure was proposed to obtain particular solutions for various types of inhomogeneous elliptic partial differential equations.This procedure employs the power series expansion of both the source function of the partial differential equation and the solution,and the problem of finding a particular solution is equivalent to solving a triangular system of linear algebraic equations.In the special case of polynomial source functions,we are often led to solving a finite triangular system.To demonstrate the effectiveness of the proposed scheme,recursive formulas for some elliptic equations were developed.Coupled with existing boundary methods for solving boundary value problems of homogeneous equations,the proposed method can be used to solve various types of partial differential equations.
Back to the Future: What Learning Communities Offer to Medical Education

Learning communities (LCs) have increasingly been incorporated into undergraduate medical education at a number of medical schools in the United States over the past decade. In an Association of Medical Colleges survey of 140 medical schools, 102 schools indicated that they had LC (described as colleges or mentorship groups; https://www.aamc.org/initiatives/cir/425510/19a.html). LCs share an overarching principle of establishing longitudinal relationships with students and faculty, but differ in the emphasis on specific components that may include curriculum delivery, advising/mentoring, student wellness, and community. The creation of LCs requires institutional commitment to reorganize educational processes to become more student centered. LCs are beginning to show positive outcomes for students including benefits related to clinical skills development, advising, and student wellness, in addition to positive outcomes for LC faculty.
Ocular cicatricial pemphigoid: case report.

Background: The main characteristic of ocular cicatricial pemphigoid is subepithelial conjunctival fibrosis, which,if if progressive, can lead to conjunctival shrinkage and symblepharon formation. Other characteristics include entropion, trichiasis, dry eye, corneal ulceration, neovascularization, and keratinization. Ultimately, blindness may occur. Cicatricial pemphigoid may also affect the skin and mucous membranes, including the nose, oral cavity, pharynx, esophagus, anus, and vagina. Treatment involves systemic immunosuppressants and corticosteroids to suppress active inflammation. Case Report: A 69-year-old man had symblephara, conjunctival shortening, and extraocular manifestations, and was diagnosed with ocular cicatricial pemphigoid on the basis of clinical appearance and immunofluorescent studies. Treatment included oral Oapsone, prednisone, and azathioprine to stabilize the condition. Conclusion: Close monitoring of ocular cicatricial pemphigoid is imperative for ocular manifestations and for extraocular complications occurring with this progressive autoimmune disease and its treatment.
BRET: NanoLuc-Based Bioluminescence Resonance Energy Transfer Platform to Monitor Protein-Protein Interactions in Live Cells

Bioluminescence resonance energy transfer (BRET) is a prominent biophysical technology for monitoring molecular interactions, and has been widely used to study protein-protein interactions (PPI) in live cells. This technology requires proteins of interest to be associated with an energy donor (i.e., luciferase) and an acceptor (e.g., fluorescent protein) molecule. Upon interaction of the proteins of interest, the donor and acceptor will be brought into close proximity and energy transfer of chemical reaction-induced luminescence to its corresponding acceptor will result in an increased emission at an acceptor-defined wavelength, generating the BRET signal. We leverage the advantages of the superior optical properties of the NanoLuc(®) luciferase (NLuc) as a BRET donor coupled with Venus, a yellow fluorescent protein, as acceptor. We term this NLuc-based BRET platform "BRET(n)". BRET(n) has been demonstrated to have significantly improved assay performance, compared to previous BRET technologies, in terms of sensitivity and scalability. This chapter describes a step-by-step practical protocol for developing a BRET(n) assay in a multi-well plate format to detect PPIs in live mammalian cells.
Information Technology Costs and Productivity Gains

This report is an overview of two strategic issues currently facing the pharmaceutical industry: the high cost of client-server computing and ensuring that investments in information technology result in productivity gains. This report begins with a discussion of the high costs involved in supporting a clientserver architecture (reported by KPMG Management Consulting and Nolan Norton & Co. to run as high as $20,000/year/PC). If a company is to maximize the returns from its current and future investment in information technology it is critical that it carefully limit the number of initiatives undertaken in this area. Companies must only undertake projects targeted at improving processes identified as critical to the success of the whole organization. Three observations drive this conclusion. One is the high cost of ownership associated with the client-server approach to computing. Two, computerization of organizations typically occurs along the vertical lines of the organizational chart and within functional departments. Three, findings indicate that the client-server architecture does not exhibit the same economies of scale associated with more traditional centralized architectures, which provide some forgiveness if trivial or peripheral applications are undertaken. These observations, coupled with the limited amount companies have to invest in information technology resources, make it critical that they carefully limit initiatives in this area.
On Identifying Human Capital: Flawed Knowledge Leads to Faulty Judgments of Expertise by Individuals and Groups

Abstract Purpose To thrive, any individual, organization, or society needs to separate true from false expertise. This chapter provides a selective review of research examining self and social judgments of human capital – that is, expertise, knowledge, and skill. In particular, it focuses on the problem of the “flawed evaluator”: most people judging expertise often have flawed expertise themselves, and thus their assessments of self and others are imperfect in profound and systematic ways. Methodology/approach The review focuses mostly on empirical work specifically building on the “Dunning–Kruger effect” in self-perceptions of expertise (Kruger & Dunning, 1999). This selective review, thus, focuses on patterns of error in such judgments. Findings Because judges of expertise have flawed expertise themselves, they fail to recognize incompetence in themselves. Because of their flaws, most people also fail to recognize genius in other people and superior ideas. Practical implications The review suggests that organizations have trouble recognizing those exhibiting the highest levels of expertise in their midst. People in organizations also fail to identify the best advice and correct flawed ideas. Organizations may also rely on the “wisdom of crowds” strategy in situations in which that strategy actually misleads because too few people identify the best idea available.
Critical Illness Neuromuscular Disease

Four children with critical illness neuromuscular disease following prolonged dependency on a ventilator are reported from the Departments of Neurology and Pediatrics, West Virginia University Health Sciences Center, Morgantown, and the Department of Medicine (Neurology), Memorial University of Newfoundland, St John’s, Canada.
Social Media Links on Magazine Advertisements: An Exploration of Consumers’ Viewpoint

The use of social media is ubiquitous in American culture. Seventy-four percent of American adults report using social networking sites; among consumers 18–29 years of age, the penetration rate is 90 % (http://www.pewinternet.org/fact-sheets/social-networking-fact-sheet/, 2014). As social media has increased in importance as a marketing medium, placement of links to social media in various outlets has become widespread. The expected advertising spend in this area is $14 billion by 2018 (http://www.businessinsider.com/social-media-advertising-spending-growth-2014-9, 2014). Moreover, the use of multiple media to reach a target audience is more prevalent than ever before. Conventional advertising on high-reach media such as television and magazines is supplanted with a mix of touch points, espousing a huge number of media alternatives (Journal of Advertising Research 53:221–230, 2013). Magazine advertisements frequently carry colorful social media icons. This qualitative study explores the attitudes of social media adopters toward these magazine links. Findings suggest that the most salient features of compelling social media links are promotional offers (such as coupons, discounts, free shipping, games, contests, or any other thing that is interesting about the company) and a clever link or hashtag keyword that facilitates easy information access about a particular product in an advertisement.
The mediating effect of family cohesion in reducing patient symptoms and family distress in a culturally informed family therapy for schizophrenia: A parallel-process latent-growth model.

Objective Although both patients with schizophrenia and their caregivers report elevated levels of depression, anxiety, and stress (DASS), affective symptoms in patients and family members seldom constitute a primary treatment focus. The present study tested whether a culturally informed family therapy for schizophrenia (CIT-S) outperformed standard family psychoeducation (PSY-ED) not only in decreasing patient schizophrenia symptoms, but also in decreasing individual DASS. Because CIT-S fostered family cohesion throughout treatment, we predicted that increases in family cohesion would mediate treatment effects. Method Participants included 266 patients and family members nested within 115 families, randomized to the CIT-S or PSY-ED conditions. We specified a series of multilevel latent growth and latent change models to examine direct effects of CIT-S on patient schizophrenia symptoms, individual DASS, and family cohesion over time. Next, we used parallel-process growth models to test the indirect effect of CIT-S on decreasing patient and caregiver psychopathology over time via changes in family cohesion. Results The CIT-S treatment significantly reduced patient schizophrenia symptoms from baseline to follow-up (γ = -1.72, 95% confidence interval [CI] [-2.83, -0.60]), as well as individual DASS (γ = -4.39, 95% CI [-6.44, -2.34]) from baseline to termination. In line with treatment goals, CIT-S increased family cohesion from baseline to midpoint (γ = 0.93, 95% CI [0.06, 1.80]). The CIT-S-related change in cohesion mediated changes in DASS (γ = -0.87, 95% CI [-1.47, -0.27]), but not patient symptoms. Conclusion By integrating the family's cultural context into treatment, clinicians may foster family dynamics that enhance treatment outcomes and promote broad improvements in mental health. (PsycINFO Database Record
Mathematics for Blind People: Introduction to the Special Thematic Session.

The ability of a blind student to pursue careers in mathematics, engineering, science or technology are severely limited by the students ability to manipulate complex mathematical equations. While there are exceptions to the rule, it has been difficult or impossible for blind members of our society to enter these career domains. The current STS deals with this problem from a broad perspective focusing on what are the best and worst practices in the area of presenting equations to blind math students.
NUMERICAL ANALYSIS OF BIPHASIC CREEP OF ARTICULAR CARTILAGE

Publisher Summary The loss of the ability of articular cartilage to withstand mechanical stresses is an important step in the pathogenesis of osteoarthritis. Thus, a full understanding of the biomechanical behavior of articular cartilage and their relationships to age, composition, and ultrastructure is of fundamental importance. Articular cartilage is a composite organic solid matrix, which is swollen by water and in which a variety of mobile electrolytes are distributed. In its adult state, cartilage generally contains by dry weight approximately 60% collagen, 30% proteoglycans, and 10% glycoproteins, lipids, and chondrolytes. In normal, fully-hydrated tissues, the fluid content is about 85% by weight, for the upper 25% of the cartilage. With increasing depth, the degree of hydration decreases to 70%. The percentage of constituents may vary with age, site in the joint, and pathological state. This chapter discusses the nonlinear biphasic constitutive equation by means of finite difference method in the solution of creep response of articular cartilage with spatially varying stiffness. The mechanical behavior of articular cartilage is best described by a two-phase system nonlinear constitutive equation.
Identification of Social Tension in Organizational Networks

Analysis of email networks reveals properties similar to classic social networks such as homophily (assortativity) and community formation. The technology underlying email enables the formation of a network but it does not explain characteristics of the network that occur only as a result of patterns in human social behavior. Accordingly, a network formed from email activity correlates to the social environment and the dynamics of the environment used to create the network. Furthermore, the overall social behavior observed in an organization may be attributed directly to the organization’s strength and resilience. When an organization is in trouble, we observe social tension among its employees. That being the case, one should be able to discern this tension by examining properties of a social network of the employees-the network should reflect the employees’mood; the fears, worries, gossips that are circulating, the good and the bad, are all reflected in organization’s social network. One of the best representations of the true social organizational social network can be constructed from email exchange. The issue we investigate in this paper relates to timing: when does the network exhibits social tension when it is known to be present in the organization? In this paper, we provide a temporal analysis of the email social network constructed for the Enron Corporation and show that changes in network characteristics strongly correlate to real-world events in that organization. More importantly, we show that this correlation is time-shifted and appears in the network before the event becomes common knowledge; our hypothesis is that we can use the anomalies in the network to identify social tension in the organization and consequently help mitigate its consequences.
Exact Boundary Controllability of a Beam and Mass System

In recent years much attention has been focused on the boundary controllability of beams. In the mathematical treatment of such problems, it is often assumed that the beam is free of loads along its length. This ideal situation is not always attainable. A beam might, for example, have small objects attached to it at various points, perhaps as part of the control mechanism. This paper investigates the exact boundary controllability of such a system. More specifically, we consider an Euler-Bernoulli Beam which is clamped at its left end and either pinned (i.e. supported) or free and attached to a point mass at its right end. We also allow the possibly of the beam being pinned at various points along its length, and of having a finite number of point masses mounted at various points along its length. We show that the system may be controlled (i.e. steered to its equilibrium state) in an arbitrarily short time interval by applying a torque to the right end of the beam.
Chemotherapy in the Management of Retinoblastoma

Treatment of retinoblastoma aims to save life and preserve useful vision, and thus needs to be individualized. Factors that need to be considered include unilaterality or bilaterality of the disease, potential for vision, and intraocular and extraocular staging. A multidisciplinary approach is pivotal, and it is in this context that the role of chemotherapy must be discussed.
Foetal diagnosis and selective abortion: an ethical exploration

Publisher Summary This chapter presents an ethical exploration of fetal diagnosis followed by selective abortion. The fetal diagnosis of some genetic disorders is possible by applying following methods: amniocentesis, intra-uterine photography, and use of ultrasound devices. However, the most effective method is amniocentesis that involves the withdrawal, by insertion of a needle, of some fluid from within the amniotic sac inside the uterus of the pregnant woman. The examination confirms the presence or absence of some—at present only a few—genetic defects. If a genetic abnormality is discovered, abortion is possible. But abortion following amniocentesis means that the woman has felt the movement of the fetus within her body; the fetus has a heartbeat and discernible brain activity; and it is hard to regard impersonally a fetus when some of its individual genetic qualities are already known. The present evidence suggests such individuals are unusually prone to acts of criminal aggression leading to institutionalization. Until the necessary large-scale surveys have been completed, it is impossible to say how prone. The ethical dilemma is made more pointed by the fact that it is not known whether an extra Y chromosome is directly causal to the difficulties in which these individuals find themselves.
Modeling and Controllability of Interconnected Elastic Membranes

A collection of systems of partial differential equations, each of which models the nonlinear deformation of an elastic membrane, is considered. The state variables of the various membranes are required to satisfy certain “geometric” and “dynamic” coupling conditions which arise from continuity and balance law considerations. The resulting coupled systems then describe the nonlinear deformations of a system of interconnected membranes. The question of exact controllability of the linearization of such a network is discussed, where the controls are in the forms of forces applied on the outer edges and in the junction regions (where membranes are connected to one another).
Fully Adaptive Remote Sensing Observing System Simulation Experiments

Future observing systems simulation experiments (OSSEs) will need to be of increased sophistication to support emerging sensors that exploit parametric adaption, resource management in constrained environments, and the collaboration of distributed sensing nodes. This paper demonstrates the power of using adaptive approaches to remote sensing through a fully adaptive radar imaging example that uses experimental data. In the demonstration, the image resolution varies between 0.47 m and 1.2 m leading to a cost metric savings of 18% and 22% compared to fixed coarse and fine resolution tests. The experimental demonstration is used to inform a discussion of how future OSSEs will need to operate.
Vancomycin does not affect the enzymatic activities of purified VanSA.

VanS is a membrane-bound sensor histidine kinase responsible for sensing vancomycin and activating transcription of vancomycin-resistance genes. In the presence of vancomycin, VanS phosphorylates the transcription factor VanR, converting it to its transcriptionally active form. In the absence of vancomycin, VanS dephosphorylates VanR, thereby maintaining it in a transcriptionally inactive state. To date, the mechanistic details of how vancomycin modulates VanS activity have remained elusive. We have therefore studied these details in an in vitro system, using the full-length VanS and VanR proteins responsible for type-A vancomycin resistance in enterococci. Both detergent- and amphipol-solubilized VanSA display all the enzymatic activities expected for a sensor histidine kinase, with amphipol reconstitution providing a marked boost in overall activity relative to detergent solubilization. A putative constitutively activated VanSA mutant (T168K) was constructed and purified, and was found to exhibit the expected reduction in phosphatase activity, providing confidence that detergent-solubilized VanSA behaves in a physiologically relevant manner. In both detergent and amphipol solutions, VanSA’s enzymatic activities were found to be insensitive to vancomycin, even at levels many times higher than the antibiotic’s minimum inhibitory concentration. This result argues against direct activation of VanSA via formation of a binary antibiotic-kinase complex, suggesting instead that either additional factors are required to form a functional signaling complex, or that activation does not require direct interaction with the antibiotic.
The Effect of an Unrestrictive Diet Program (iDip) on Weight Management with Primary Focus on Protein and Fiber Intake and Calorie Reduction (P21-010-19)

Objectives To develop a cost-effective program for safe weight loss and sustainable maintenance for overweight adults with associated comorbidities through dietary modifications.
A data ensemble approach for real-time air quality forecasting using extremely randomized trees and deep neural networks

Six generalized machine learning (ML) ensemble models were developed to predict the real-time hourly ozone concentration of the following day. These models were used to forecast hourly ozone concentrations of the following day for all of 2017 in the city of Seoul, South Korea. To prepare the training dataset, it was referred to observed meteorology and air pollution parameters of the 2014–2016 period. The ensemble models fuse two regression models: a low-ozone peak model and a high-ozone model. For both, extremely randomized trees and deep neural networks were used. A regularization approach was also adopted that adjusts the model toward capturing higher ozone peaks by resampling the training dataset based on the peaks. Adopting the proposed ML ensemble forecasting method over single-model ML techniques as a part of mainstream practice for air quality forecasting will be beneficial for several reasons. For one, the proposed method, which captures daily maximum ozone concentrations during the high-ozone season (April–September), reduces the ozone peak prediction error by 5 to 30 ppb. In addition, compared to station-specific (independent) ML models with more frequent low-ozone values, models are trained with a uniformly distributed dataset, so they are more generalizable in nature. As a result, unlike station-specific models, they retain their accuracy (yearly IOA = 0.84–0.89) in all stations with an IOA increment. Proposed models also make predictions several times faster, requiring only one-time training for predicting an entire station network. Based on a categorical analysis of the training dataset, an algorithm was proposed for selecting the most suitable model for each month. The “best” model further improves the accuracy of both the ML ensemble and individual models by up to 2.4%. This study shows that the ML ensemble modeling approach is a fast, reliable, and robust technique that can benefit environmental decision-makers in urban regions.
The Promise of International Law in Developing a Global Foundation for Social Justice

Notions of human rights and social justice have become so intertwined that today one can enroll in an academic program that leads to an MA degree in “Social Justice and Human Rights.” The emergence of this interdisciplinary field of study, on the one hand, seems a perfectly natural recognition of the long-standing affinity shared by these two concepts. Yet, on the other, the merger also reasonably may strike one as an exceedingly amorphous frame of reference for advanced education, if only because both concepts are subject to myriad of, and sometimes contesting, definitions. For example, viewed from the perspective of Glenn Beck, such a program could be equated with the curriculum of a Marxist re-education camp if it dared move beyond a one-dimensional, religiously infused mission of helping the poor! At the same time, restricting the definition of social justice in this manner would appear to run against the spirit underpinning the very term. Likewise, human rights, almost from the outset, have been subject to competing visions that grapple, among other things, between the political and economic as well as the universalist and relativist.Inevitably, preliminary questions arise as to what definition of human rights and whose social justice is being held out as a baseline when engaging in this complex and often controversial area. But rather than be preoccupied with this definitional quagmire, I instead propose in this brief chapter the modest task of highlighting the relevancy of modern international human rights law as a transnational lingua franca for framing and promoting social justice advocacy on the ground.
Ripensare le politiche macroeconomiche: evoluzione o rivoluzione? (Evolution or Revolution? Rethinking Macroeconomic Policy after the Great Recession)

L’ovvia lezione della Grande crisi finanziaria e che il sistema finanziario conta e che altre crisi finanziarie probabilmente si verificheranno di nuovo. La seconda lezione, piu generale, e che spesso l’economia non e in grado di auto-stabilizzarsi. Queste due lezioni, in un contesto in cui i tassi d’interesse “neutrali” dovrebbero rimanere bassi, hanno chiare implicazioni per la progettazione delle politiche di stabilizzazione. Come minimo, esse suggeriscono che le politiche potrebbero dover diventare piu aggressive, sia ex ante che ex post, con un ribilanciamento di ruoli tra politiche monetarie, fiscali e finanziarie. In particolare, bassi tassi “neutrali” riducono i margini d’azione della politica monetaria, ma aumentano la possibilita di utilizzo della politica fiscale. Pensiamo a tale ribilanciamento come una evoluzione. Se tuttavia, i tassi “neutrali” diventeranno ancor piu bassi o la regolamentazione finanziaria risultera insufficiente per prevenire le crisi, potranno rendersi necessarie misure ancor piu drastiche, inclusi piu ampi disavanzi di bilancio, revisioni degli obiettivi di politica monetaria o restrizioni piu severe sul sistema finanziario. Pensiamo a tutto questo come una rivoluzione. Il tempo ci dira. The obvious lesson from the Great Financial Crisis is that the financial system matters and financial crises will probably happen again. The second, more general, lesson is that the economy is often not self-stabilizing. These two lessons, together with an environment where “neutral” interest rates are likely to remain low, have clear implications for the design of stabilization policies. At a minimum, they suggest that policies may need to become more aggressive, both ex-ante and ex-post, with a rebalancing of the roles of monetary, fiscal and financial policies. In particular, while low “neutral” rates decrease the scope for using monetary policy, they increase the scope for using fiscal policy. Think of such rebalancing as evolution. If however, “neutral” rates become even lower, or financial regulation turns out to be insufficient to prevent crises, more dramatic measures, including larger fiscal deficits, revised monetary policy targets, or sharper restrictions on the financial system, may be needed. Think of this as revolution. Time will tell. JEL codes : E02, E20, E31, E32, E42, E5, E62
A Mount Laurel for Climate Change? The Judicial Role in Reducing Greenhouse Gas Emissions from Land Use and Transportation

Greenhouse gas emissions from transportation in the United States have remained persistently high. One cause is common low-density land use patterns that make most Americans dependent on automobiles. Reducing these emissions requires increasing density, which U.S. local government law makes difficult to achieve through the political process. Mount Laurel, a 1975 New Jersey Supreme Court case that addressed an affordable housing crisis by restraining local parochialism, provides a potential solution. Environmental advocates may be able to mount similar state-law challenges against low-density zoning based on the high carbon emissions it produces. Such a challenge is legally and normatively defensible in New Jersey and other states.
A Neuropsychological Profile for Cerebrotendinous Xanthomatosis: A Single-Case Study.

Objective:Cerebrotendinous xanthomatosis (CTX) belongs to a heterogeneous group of neurological disorders known as autosomal recessive cerebellar ataxias. Low awareness of CTX can result in misdiagnoses in the differential diagnostic process and may limit one’s ability to offer suitable recommendations. While neurodegeneration is a recognized manifestation of CTX, there is scant literature to characterize the nature of cortical symptoms and even less detailing of its associated neurocognitive and neuropsychiatric manifestations.Method:Based on the lack of representation of CTX in neuropsychological literature, we sought to present a case seen in a 39-year-old patient within our own clinic.Results:Evaluation of the patient’s neurocognitive functioning revealed global impairment consistent with a CTX diagnosis and neuroimaging findings noting significant cerebellar involvement.Conclusions:Neuropsychologists are increasingly called upon to make treatment recommendations and provide information that may be helpful in differential diagnosis as part of multidisciplinary teams. Referrals from neurology are common, and it is important for neuropsychologists to be aware of diseases that affect the central nervous system; CTX is one such example. The goal of this case study is to build awareness of this condition and increase interest in a more systematic approach to research and clinical care of this population.
Comparative nonclinical assessments of the biosimilar PF-06410293 and originator adalimumab.

Abstract Adalimumab, a recombinant fully human monoclonal antibody targeting tumor necrosis factor (TNF), is approved in the United States and Europe to treat various inflammatory and autoimmune indications. Biosimilars are approved biologics highly similar, but not identical, to approved biotherapeutics. To support clinical development of PF-06410293, an adalimumab biosimilar, nonclinical studies evaluated the structural, functional, toxicologic, and toxicokinetic similarity to originator adalimumab sourced from the United States (adalimumab-US) and European Union (adalimumab-EU). Structural similarity was assessed by peptide mapping. Biologic activity was measured via inhibition of TNF-induced apoptosis and Fc-based functionality assessments. In vivo nonclinical similarity was evaluated in a toxicity study in cynomolgus monkeys administered subcutaneous PF-06410293 or adalimumab-EU (0 or 157 mg/kg/week). Peptide mapping demonstrated PF-06410293, adalimumab-US, and adalimumab-EU had identical amino acid sequences. Comparative functional and binding assessments were similar. Effects of PF-06410293 and adalimumab-EU were similar and limited to pharmacologically mediated decreased cellularity of lymphoid follicles and germinal centers in spleen. Toxicokinetics were similar; maximum plasma concentration and area-under-the-concentration-time curve ratio of PF-06410293:adalimumab-EU ranged from 1.0 to 1.2. These studies supported PF-06410293 entry into clinical development. Many regulatory agencies now only request nonclinical in vivo testing if there is residual uncertainty regarding biosimilarity after in vitro analytical studies.
RISE registry reveals potential gaps in medication safety for new users of biologics and targeted synthetic DMARDs.

Abstract Objective Immunosuppressant drugs can increase the risk of hepatitis B virus (HBV) and hepatitis C virus (HCV) and tuberculosis (TB) reactivation. Using the American College of Rheumatology's Rheumatology Informatics System for Effectiveness (RISE) registry, we examined pre-treatment screening among new users of biologic or targeted synthetic disease modifying drugs (DMARDs). Methods Data, derived from RISE, included patients ≥ 18 years old who were new users of biologic or targeted synthetic DMARDs. We developed quality measures related to pre-treatment screening for HBV, HCV, and TB in addition to a “composite” measure for all applicable tests. We assessed patient-level screening rates, practice-level variation among practices reporting on ≥ 20 patients, and the frequency of positive results. Results We included 26,802 patients across 213 rheumatology practices nationwide. Patients were 58 (14) years old, 75.9% female; 59.6% had rheumatoid arthritis, and TNFi were the most common index DMARDs (64.9%). Overall, 44.8% and 40.5% patients had any documented HBV or HCV screening, respectively, prior to the index date; 29.7% had TB screening in the year prior to drug start. Only 15.5% had documentation of screening for all appropriate infections prior to drug start. Practice-level performance on the composite measure was low (range 0 to 48.3%). 2.4% of screening tests were positive. Conclusion We found gaps in documentation of key safety measures among practices participating in RISE. Given the small but significant number of patients with active or latent infections that pose safety risks, developing standardized and reliable strategies to capture safety screening measures is paramount.
Enhanced alcohol production over binary Mo/Co carbide catalysts in syngas conversion

Abstract Recently metal carbide catalysts have attracted attention as alternatives to pure metals for the conversion of syngas to higher oxygenates, a process which could enable the sustainable production of fuels, polymers, and chemicals. Although Mo and Co carbides have both shown promise for higher oxygenate production, they have not achieved the requisite activity and selectivity for practical implementation. In this work we synthesize and characterize a binary Mo and Co carbide catalyst that exhibits improved activity and oxygenate selectivity relative to either pure metal carbide. We apply a combination of advanced electron microscopy and X-ray diffraction to show that the binary Mo/Co carbide catalyst forms uniformly mixed amorphous nanoparticles. Through in situ X-ray absorption spectroscopy studies, we determine that the structure of the mixed metal carbide catalyst under reaction conditions consists of both carbidic and bimetallic components. By testing the catalytic properties of a series of Mo/Co carbide catalysts prepared by different synthesis methods, we find that the Mo and Co sites must be in close contact to achieve improved syngas conversion to higher alcohols. Through in situ DRIFTS measurements, both Mo and Co atoms at the surface of the catalyst are identified as adsorption sites for reactive species.
Genomic Mechanisms Governing Mineral Homeostasis and the Regulation and Maintenance of Vitamin D Metabolism

Our recent genomic studies identified a complex kidney-specific enhancer module located within the introns of adjacent Mettl1 (M1) and Mettl21b (M21) genes that mediate basal and PTH induction of Cyp27b1, as well as suppression by FGF23 and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. The tissue specificity for this regulatory module appears to be localized exclusively to renal proximal tubules. Gross deletion of these segments in mice has severe consequences on skeletal health, and directly affects Cyp27b1 expression in the kidney. Deletion of both the M1 and M21 submodules together almost completely eliminates basal Cyp27b1 expression in the kidney, creating a renal specific pseudo-null mouse, resulting in a systemic and skeletal phenotype similar to that of the Cyp27b1-KO mouse caused by high levels of both 25-hydroxyvitamin D3 [25(OH)D3] and PTH and depletion of 1,25(OH)2D3. Cyp24a1 levels in the double KO mouse also decrease because of compensatory downregulation of the gene by elevated PTH and reduced FGF23 that is mediated by an intergenic module located downstream of the Cyp24a1 gene. Outside of the kidney in nonrenal target cells (NRTCs), expression of Cyp27b1 in these mutant mice was unaffected. Dietary normalization of calcium, phosphate, PTH, and FGF23 rescues the aberrant phenotype of this mouse and normalizes the skeleton. In addition, both the high levels of 25(OH)D3 were reduced and the low levels of 1,25(OH)2D3 were fully eliminated in these mutant mice as a result of the rescue-induced normalization of renal Cyp24a1. Thus, these hormone-regulated enhancers for both Cyp27b1 and Cyp24a1 in the kidney are responsible for the circulating levels of 1,25(OH)2D3 in the blood. The retention of Cyp27b1 and Cyp24a1 expression in NRTCs of these endocrine 1,25(OH)2D3-deficient mice suggests that this Cyp27b1 pseudo-null mouse will provide a model for the future exploration of the role of NRTC-produced 1,25(OH)2D3 in the hormone's diverse noncalcemic actions in both health and disease. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.