bluuebunny/crossref_metadata_2025 huggingface dataset:
Constructing Quantum Mechanics
Authors: Duncan Anthony , Janssen Michel
Published: October 2019

This is the first of two volumes on the genesis of quantum mechanics. It covers the key developments in the period 1900–1923 that provided the scaffold on which the arch of modern quantum mechanics was built in the period 1923–1927 (covered in the second volume). After tracing the early contributions by Planck, Einstein, and Bohr to the theories of black‐body radiation, specific heats, and spectroscopy, all showing the need for drastic changes to the physics of their day, the book tackles the efforts by Sommerfeld and others to provide a new theory, now known as the old quantum theory. After some striking initial successes (explaining the fine structure of hydrogen, X‐ray spectra, and the Stark effect), the old quantum theory ran into serious difficulties (failing to provide consistent models for helium and the Zeeman effect) and eventually gave way to matrix and wave mechanics. Constructing Quantum Mechanics is based on the best and latest scholarship in the field, to which the authors have made significant contributions themselves. It breaks new ground, especially in its treatment of the work of Sommerfeld and his associates, but also offers new perspectives on classic papers by Planck, Einstein, and Bohr. Throughout the book, the authors provide detailed reconstructions (at the level of an upper‐level undergraduate physics course) of the cental arguments and derivations of the physicists involved. All in all, Constructing Quantum Mechanics promises to take the place of older books as the standard source on the genesis of quantum mechanics.
Only God Can Make a Tree
Authors: Martin Christopher J.
Published: October 2019

sProblems about the nature of integral parts and wholes were central to twelfth-century discussions of the individuation and persistence over time of both substances and artifacts. This paper examines in detail Abaelard’s contribution to these discussions arguing that Abaelard proposes a solution to these problems which preserves our common sense intuitions about identity over time. In Abaelard’s work we find an explicit solution to the problem of the identity over time of living things which appeals to the persistence of the vegetative soul through the loss or addition of corporeal matter. In work from the school of the Montani we apparently also have an account of Abaelard’s solution to the problem of the identity over time of artifacts which distinguishes between the role of a part in an integral whole and the material which plays that role such that the role persists when the matter is replaced.
The Emergence of the Robo-Advisor
Authors: Fisch Jill E. , Labouré Marion , Turner John A.
Published: October 2019

Robo-advisors are online services that use computer algorithms to provide financial advice and manage customers’ investment portfolios. This chapter describes the development of the robo-advisor industry and compares robo-advisors to traditional human financial advisors. Robo-advisors emerged in response to people’s need for financial advice and the high cost of obtaining that advice from human advisors. Pure robo-advisors, which offer no direct human contact, are generally substantially less expensive than human advisors, and the use of computer algorithms allows for an increasing degree of personalization of the advice. Nevertheless, robo-advisors do not provide customers with all of the services offered by human advisors and, in particular, human contact. In response, some firms are offering hybrid robo/human services that combine cost savings from a robo-advisor with some human input.
Behavioral Finance, Decumulation, and the Regulatory Strategy for Robo-Advice
Authors: Baker Tom , Dellaert Benedict
Published: October 2019

This chapter examines the regulatory and market structure concerns raised by automated financial advisors, and arrives at two conclusions. First, the principles-based regulatory approach of the 1940 Investment Advisors Act in the U.S. appears adequate and sufficiently flexible to address the new issues raised by automation, at least for now. Second, there is a pressing need to develop new mechanisms for encouraging investment robo-advisors (and financial advisors generally) to provide high quality decumulation services to their customers, because neither of the two prevailing compensation approaches—assets under management and commissions—provides sufficient incentive at present, and consumers are poorly equipped to evaluate the quality of decumulation services on their own.
The Ends of Kinship in the French Romantic Novel
Authors: Britton Jeanne M.
Published: October 2019

René and Atala by François-René de Chateaubriand and Paul et Virginie by Jacques-Henri Bernardin de Saint-Pierre each specify a novelistic version of sympathy that arises when stories of forbidden sibling attachment that threaten incest pass between figurative fathers and sons. These texts did not begin as novels, and their internal stories of textual genesis suggest that a particular model of sympathy shapes the transformation of narrative episode into stand-alone novel. In each of these novels, which were popular after the French Revolution’s critique of paternity and its cry of fraternité, siblinghood poses problems of extreme resemblance, a stymied present, and a resistance to the representation and transmission of narrative. Kinship metaphors in scenes of narrative transmission suggest that in order to become independent works of fiction, these extracted episodes rely in part on the accommodated differences, temporal progression, and narrative channels that figurative relationships of paternity offer.
Standards of diagnostic assessment for autism spectrum disorder
Authors: Brian Jessica A , Zwaigenbaum Lonnie , Ip Angie
Published: October 2019

The rising prevalence of autism spectrum disorder (ASD) has created a need to expand ASD diagnostic capacity by community-based paediatricians and other primary care providers. Although evidence suggests that some children can be definitively diagnosed by 2 years of age, many are not diagnosed until 4 to 5 years of age. Most clinical guidelines recommend multidisciplinary team involvement in the ASD diagnostic process. Although a maximal wait time of 3 to 6 months has been recommended by three recent ASD guidelines, the time from referral to a team-based ASD diagnostic evaluation commonly takes more than a year in many Canadian communities. More paediatric health care providers should be trained to diagnose less complex cases of ASD. This statement provides community-based paediatric clinicians with recommendations, tools, and resources to perform or assist in the diagnostic evaluation of ASD. It also offers guidance on referral for a comprehensive needs assessment both for treatment and intervention planning, using a flexible, multilevel approach.
Nuclear statistical equilibrium equation of state with a parametrized Dirac–Brückner Hartree–Fock calculation
Authors: Furusawa Shun , Togashi Hajime , Sumiyoshi Kohsuke , Saito Koichi , Yamada Shoichi , Suzuki Hideyuki
Published: October 2019

We calculate new equations of state (EOSs) for astrophysical simulations in the framework of the extended nuclear statistical equilibrium, in which we minimize the free energy density for the full ensemble of nuclei in a hot and dense stellar environment. To evaluate bulk and surface energies of heavy nuclei and free energies of uniformly distributed nucleons, we use fitting formulae for the interaction energies and single-nucleon potentials at zero temperature of a Dirac–Brückner Hartree–Fock (DBHF) theory, one of the modern approaches to describe homogeneous nuclear matter. We find that the DBHF EOS exhibits larger mass fractions for medium-mass nuclei and smaller mass fractions for the other nuclei than the EOS obtained using the variational method (VM), another modern model for homogeneous nuclear matter. This effect is due to the more deeply bound energy for symmetric nuclear matter and the larger symmetry energy encoded in the DBHF EOS. At supra-nuclear densities, the DBHF EOS exhibits characteristics of a larger free energy, a higher pressure, and a larger neutron chemical potential of neutron-rich matter, which lead to a larger radius of cold neutron stars than that obtained by the VM EOS.
How Acquisitions Affect Firm Behavior and Performance: Evidence from the Dialysis Industry*
Authors: Eliason Paul J , Heebsh Benjamin , McDevitt Ryan C , Roberts James W
Published: October 2019

Many industries have become increasingly concentrated through mergers and acquisitions, which in health care may have important consequences for spending and outcomes. Using a rich panel of Medicare claims data for nearly one million dialysis patients, we advance the literature on the effects of mergers and acquisitions by studying the precise ways providers change their behavior following an acquisition. We base our empirical analysis on more than 1,200 acquisitions of independent dialysis facilities by large chains over a 12-year period and find that chains transfer several prominent strategies to the facilities they acquire. Most notably, acquired facilities converge to the behavior of their new parent companies by increasing patients’ doses of highly reimbursed drugs, replacing high-skill nurses with less-skilled technicians, and waitlisting fewer patients for kidney transplants. We then show that patients fare worse as a result of these changes: outcomes such as hospitalizations and mortality deteriorate, with our long panel allowing us to identify these effects from within-facility or within-patient variation around the acquisitions. Because overall Medicare spending increases at acquired facilities, mostly as a result of higher drug reimbursements, this decline in quality corresponds to a decline in value for payers. We conclude the article by considering the channels through which acquisitions produce such large changes in provider behavior and outcomes, finding that increased market power cannot explain the decline in quality. Rather, the adoption of the acquiring firm’s strategies and practices drives our main results, with greater economies of scale for drug purchasing responsible for more than half of the change in profits following an acquisition.
miR‐223‐3p promotes autoreactive Th17 cell responses in experimental autoimmune uveitis (EAU) by inhibiting transcription factor FOXO3 expression
Authors: Wei Yankai , Chen Sisi , Sun Deming , Li Xue , Wei Ruihua , Li Xiaorong , Nian Hong
Published: October 2019

Pathogenic T helper (Th)17 cells are key mediators of autoimmune diseases such as uveitis and its animal model, experimental autoimmune uveitis (EAU). However, the contribution of microRNAs (miRs) to the intrinsic control of pathogenic Th17 cells in EAU remains largely unknown. Here, we have reported that miR‐223‐3p was significantly up‐regulated in interphotoreceptor retinoid‐binding protein‐specific Th17 cells, and its expression was enhanced by IL‐23‐signal transducer and activator of transcription 3 signaling. Knockdown of miR‐223‐3p decreased the pathogenicity of Th17 cells in a T‐cell transfer model of EAU. Mechanistic studies showed that miR‐223‐3p directly repressed the expression of forkhead box O3 (FOXO3), and FOXO3 negatively regulated pathogenic Th17 cell responses partially via suppression of IL‐23 receptor expression. Thus, our results reveal an important role for miR‐223‐3p in autoreactive Th17 cell responses and suggest a potential therapeutic avenue for uveitis.—Wei, Y., Chen, S., Sun, D., Li, X., Wei, R., Li, X., Nian, H. miR‐223‐3p promotes autoreactive Th17 cell responses in experimental autoimmune uveitis (EAU) by inhibiting transcription factor FOXO3 expression. FASEB J. 33, 13951‐13965 (2019). www.fasebj.org
Genome-wide Transcriptomic Analysis of the Response ofBotrytis cinereato Wuyiencin
Authors: Shi Liming , Liu Binghua , Wei Qiuhe , Ge Beibei , Zhang Kecheng
Published: October 2019

Grey mould is caused by the ascomycetesBotrytis cinereain a range of crop hosts. As a biological control agent, the nucleoside antibiotic wuyiencin has been industrially produced and widely used as an effective fungicide. To elucidate the effects of wuyiencin on the transcriptional regulation inB. cinerea, we, for the first time, report a genome-wide transcriptomic analysis ofB. cinereatreated with wuyiencin. We could identify 2067 differentially expressed genes (DEGs); of them, 886 and 1181 genes were significantly upregulated and downregulated, respectively. Functional categorization indicated that genes involved in amino acid metabolism and those encoding putative secreted proteins were remarkably influenced in response to wuyiencin treatment. Moreover, the expression of genes involved in protein synthesis and energy metabolism (oxidative phosphorylation) and of those encoding ATP-binding cassette transporters was markedly upregulated, whereas that of genes participating in DNA replication, cell cycle, and stress response was downregulated. Furthermore, wuyiencin resulted in mycelial malformation and negatively influenced cell growth rate and conidial yield inB. cinerea. Our results suggest that this nucleoside antibiotic regulates all aspects of cell growth and differentiation inB. cinerea. To summarize, we identified candidate pathways and target genes that may offer insights into the protective and antagonistic mechanisms underlying the action of biological control agents.
Targeting AGTR1/NF-κB /CXCR4 axis by miR-155 attenuates oncogenesis in Glioblastoma
Authors: Singh Anukriti , Srivastava Nidhi , Ateeq Bushra
Published: October 2019

Glioblastoma (GBM) represents the most aggressive malignancy of the brain. Angiotensin II Receptor Type 1 (AGTR1) upregulation has been associated with proliferative and infiltrative properties of glioma cells. However, the underlying mechanism of AGTR1 upregulation in GBM is still unexplored. To understand the post-transcriptional regulation ofAGTR1in GBM, we screened 3’untranslated region (3’UTR) ofAGTR1by using prediction algorithms for binding of miRNA. Interestingly, miR-155 showed conserved binding on the 3’UTR ofAGTR1, subsequently confirmed byAGTR1-3’UTR-luciferase reporter assay. Furthermore, stable miR-155 overexpressing GBM cells show decrease in AGTR1-mediated cell proliferation, invasion, foci formation and anchorage-independent growth. Strikingly, immunodeficient mice implanted with stable miR-155 overexpressing SNB19 cells show remarkable reduction (∼95%) in tumor burden compared to control. Notably, miR-155 attenuates NF-κB signaling downstream of AGTR1 leading to reduced CXCR4 and AGTR1 levels. Mechanistically, miR-155 mitigates AGTR1-mediated, angiogenesis, epithelial-to-mesenchymal transition, stemness, ERK/MAPK signaling and promotes apoptosis. Similar effects in cell-based assays were observed by using pharmacological inhibitor of IκB Kinase (IKK) complex. Taken together, we established that miRNA-155 post-transcriptionally regulatesAGTR1expression, abrogates AGTR1/NF-κB/CXCR4 signaling axis and elicits pleiotropic anticancer effects. This study opens new avenues for using IKK inhibitors and miRNA-155 replacement therapies for the treatment of AGTR1-positive malignancies.
GAD: a Python script for dividing genome annotation files into feature-based files
Authors: Karam Ahmed , Yasser Norhan
Published: October 2019

Nowadays, manipulating and analyzing publicly available genomic datasets become a daily task in bioinformatics and genomics laboratories. The release of several genome sequencing projects prompts bioinformaticians to develop automated scripts and pipelines which analyze genomic datasets in particular gene annotation pipelines. Handling genome annotation files with fully-featured programs used by non-developers is necessary, furthermore, accelerating genomic data analysis with a focus on diminishing the genome annotation and sequence files based on specific features is required. Consequently, to extract genome features from GTF or GFF3 in a precise manner, GAD script (https://github.com/bio-projects/GAD) provides a simple graphical user interface which interpreted by all python versions installed in different operating systems. GAD script contains unique entry widgets which are capable to analyze multiple genome sequence and annotation files by a click. With highly influential coded functions, genome features such upstream genes, downstream genes, intergenic regions, genes, transcripts, exons, introns, coding sequences, five prime untranslated regions, and three prime untranslated regions and other ambiguous sequence ontology terms will be extracted. GAD script outputs the results in diverse file formats such as BED, GTF/GFF3 and FASTA files which supported by other bioinformatics programs. Our script could be incorporated into various pipelines in all genomics laboratories with the aim of accelerating data analysis.
Copper is an essential regulator of the autophagic kinases ULK1/2 to drive lung adenocarcinoma
Authors: Tsang Tiffany , Posimo Jessica M. , Gudiel Andrea A. , Cicchini Michelle , Feldser David M. , Brady Donita C.
Published: October 2019

Targeting aberrant kinase activity in cancer relies on unmasking cellular inputs such as growth factors, nutrients, and metabolites that contribute to cancer initiation and progression1. While the transition metal copper (Cu) is an essential nutrient that is traditionally viewed as a static cofactor within enzyme active sites2, a newfound role for Cu as a modulator of kinase signaling is emerging3, 4. We discovered that Cu is required for the activity of the autophagic kinases ULK1/2 through a direct Cu-ULK1/2 interaction. Genetic loss of the Cu transporterCtr1or mutations in ULK1 that disrupt Cu-binding reduced ULK1/2-dependent signaling and autophagosome complex formation. Elevated intracellular Cu levels are associated with starvation induced autophagy and sufficient to enhance ULK1 kinase activity and in turn autophagic flux. Targeting autophagy machinery is a promising therapeutic strategy in cancers5, but is limited by the absence of potent inhibitors and the emergence of resistance. The growth and survival of lung tumors driven by KRASG12Dis diminished in the absence ofCtr1, depends on ULK1 Cu-binding, and is associated with reduced autophagy levels and signaling. These findings suggest a new molecular basis for exploiting Cu-chelation therapy to forestall autophagy signaling to limit proliferation and survival in cancer.
Thermal versus Mechanical Unfolding in a Model Protein
Authors: Tapia-Rojo Rafael , Mazo Juan J. , Falo Fernando
Published: October 2019

Force spectroscopy techniques are often used to learn about the free energy landscape of single biomolecules, typically by recovering free energy quantities that, extrapolated to zero force, are compared to those measured in bulk experiments. However, it is not always clear how the information obtained from a mechanically perturbed system can be related to that obtained using other denaturants, since tensioned molecules unfold and refold along a reaction coordinate imposed by the force, which is unlikely meaningful in its absence. Here, we explore this dichotomy by investigating the unfolding landscape of a model protein, which is first unfolded mechanically through typical force spectroscopy-like protocols, and next thermally. When unfolded by non-equilibrium force extension and constant force protocols, we recover a simple two-barrier landscape, as the protein reaches the extended conformation through a metastable intermediate. Interestingly, folding-unfolding equilibrium simulations at low forces suggested a totally different scenario, where this metastable state plays little role in the unfolding mechanism, and the protein unfolds through two competing pathways27. Finally, we use Markov state models to describe the configurational space of the unperturbed protein close to the critical temperature. The thermal dynamics is well understood by a one-dimensional landscape along an appropriate reaction coordinate, however very different from the mechanical picture. In this sense, in our protein model the mechanical and thermal descriptions provide incompatible views of the folding/unfolding landscape of the system, and the estimated quantities to zero force result hard to interpret.
CTRL: a label-free method for dynamic measurement of single-cell volume
Authors: Yao Kai , Rochman Nash D. , Sun Sean X.
Published: October 2019

Measuring the physical size of the cell is valuable in understanding cell growth control. Current single-cell volume measurement methods for mammalian cells are labor-intensive, inflexible, and can cause cell damage. We introduce CTRL: Cell Topography Reconstruction Learner, a label-free technique incorporating Deep Learning and Fluorescence Exclusion for reconstructing cell topography and estimating mammalian cell volume from DIC microscopy images alone. The method achieves quantitative accuracy, requires minimal sample preparation, and applies to extensive biological and experimental conditions. Using this method, we observe a noticeable reduction in cell size fluctuations during cell cycle, which is consistent with the presence of a cell size checkpoint. (https://GitHub.com/sxslabjhu/CTRL)
Crystal structure of the putative cyclase IdmH from the indanomycin nonribosomal peptide synthase/polyketide synthase
Authors: Drulyte Ieva , Obajdin Jana , Trinh Chi H. , Kalverda Arnout P. , van der Kamp Marc W. , Hemsworth Glyn R. , Berry Alan
Published: October 2019

Indanomycin is biosynthesized by a hybrid nonribosomal peptide synthase/polyketide synthase (NRPS/PKS) followed by a number of `tailoring' steps to form the two ring systems that are present in the mature product. It had previously been hypothesized that the indane ring of indanomycin was formed by the action of IdmH using a Diels–Alder reaction. Here, the crystal structure of a selenomethionine-labelled truncated form of IdmH (IdmH-Δ99–107) was solved using single-wavelength anomalous dispersion (SAD) phasing. This truncated variant allows consistent and easy crystallization, but importantly the structure was used as a search model in molecular replacement, allowing the full-length IdmH structure to be determined to 2.7 Å resolution. IdmH is a homodimer, with the individual protomers consisting of an α+β barrel. Each protomer contains a deep hydrophobic pocket which is proposed to constitute the active site of the enzyme. To investigate the reaction catalysed by IdmH, 88% of the backbone NMR resonances were assigned, and using chemical shift perturbation of [15N]-labelled IdmH it was demonstrated that indanomycin binds in the active-site pocket. Finally, combined quantum mechanical/molecular mechanical (QM/MM) modelling of the IdmH reaction shows that the active site of the enzyme provides an appropriate environment to promote indane-ring formation, supporting the assignment of IdmH as the key Diels–Alderase catalysing the final step in the biosynthesis of indanomycin through a similar mechanism to other recently characterized Diels–Alderases involved in polyketide-tailoring reactions. An animated Interactive 3D Complement (I3DC) is available in Proteopedia at https://proteopedia.org/w/Journal:IUCrJ:S2052252519012399.
Decacarbonyl(μ-ethylidenimino-1κN:2κC)-μ-hydrido-triangulo-triosmium(3 Os–Os)
Authors: Powell Cynthia B. , Powell Gregory L. , Archambeau Ashley K. , Wilson Kylie M.
Published: October 2019

The title complex, [Os3(C2H4N)H(CO)10] or [Os3(CO)10(μ-H)(μ-HN=C—CH3-1κN:2κC)], was synthesized in 41.6% yield by reactions between Os3(CO)11(CH3CN) and 2,4,6-trimethylhexahydro-1,3,5-triazine. The central osmium triangle has two OsI atoms bridged by a hydride ligand and a μ-HN= C—CH3-1κN:2κC triazine fragment. Three CO ligands complete the coordination sphere around each OsI atom, while the remaining Os0 atom has four CO ligands. Each Os atom exhibits a pseudo-octahedral coordination environment, discounting the bridging Os—Os bond.
Distributed dissipative filtering for flexible manipulator with randomly occurring uncertainties and missing data
Authors: Zhang Xiaodong , Xiao Tao
Published: October 2019

Purpose

The purpose of this paper is to investigate the dissipative filtering problem for a flexible manipulator (FM) with randomly occurring uncertainties and randomly occurring missing data.

Design/methodology/approach

The randomly occurring phenomena during the filtering procedure are described by Bernoulli sequences. Based on the idea of dissipative theory, the distributed filtering error augmented system is derived for ensuring the prescribed dissipative performance.

Findings

By constructing appropriate Lyapunov function, sufficient dissipative filtering conditions are derived such that the filtering error can be approaching zero. Then, the desired distributed filter gains are designed with the help of matrix transformation.

Originality/value

The merit of this paper is proposing a novel distributed filtering framework for an FM with external disturbance under the dissipative framework, which can provide a more applicable filter design.
Exploring the dual effects of perceived waiting on healthcare service satisfaction among outpatients
Authors: Liu Yi-Fen , Liao Jun-Fang , Jou Jacob
Published: October 2019

Purpose

The purpose of this paper is to explore healthcare waiting time and the negative and positive effects (i.e. the dual effects) it has on outpatient satisfaction.

Design/methodology/approach

Self-administered surveys with 334 outpatients and follow-up interviews with 20 outpatients in three large hospitals in Taiwan were conducted to collect data.

Findings

Quantitative surveys demonstrated that perceived waiting time correlated with satisfaction negatively first but then positively. Satisfaction also correlated with doctor reputation and patient sociability. Follow-up qualitative interviews further revealed that, for some patients, waiting contributed positively to patient evaluations through signaling better healthcare quality and facilitating social interaction.

Originality/value

This research demonstrated the possibility that waiting might have positive effects on healthcare satisfaction. It also identified variables that could produce greater positive perceptions during hospital waiting and underlying mechanisms that could explain how the positive effects work. This research may potentially help hospitals with a better understanding of how they can improve patients’ waiting experiences and increase satisfaction.
Cryptoliquidity: the blockchain and monetary stability
Authors: Caton James Lee
Published: October 2019

Purpose

The development of blockchain and cryptocurrency may alleviate the economic strain associated with recession. Economic recessions tend to be aggregate-demand driven, meaning that they are caused by fluctuations in the supply of or demand for money. Holding monetary policy as solution assumes that stability must arise from outside of the economic system. Under a policy regime that allows innovations in blockchain to develop, blockchain technology may promote a money supply that is responsive to changes in demand to hold money. The purpose of this paper is to suggest that cryptocurrencies present an opportunity to profitably implement rules that promote macroeconomic stability. In particular, cryptocurrency that is asset-backed may provide a means for cheaply attaining liquidity during a crisis.

Design/methodology/approach

The role of cryptocurrency in promoting macroeconomic equilibrium is approached through the lens of monetary theory. Moves away from macroeconomic equilibrium necessitate either a change in the average price of money or a change in the quantity of money, or a change in portfolio demand for money. Cryptocurrency promotes an increase, however this requires the alignment of policy regulating the use of cryptocurrency, reduction in taxes placed on the use of cryptocurrency and cryptocurrency protocol.

Findings

Cryptocurrency is unlikely to become legal tender, but it may alleviate macroeconomic fluctuations as a near money that provides liquidity and whose supply is sensitive to changes in demand to hold money and money-like substitutes. This role might be inhibited if policy stifles the development of cryptocurrencies and blockchain technology.

Research limitations/implications

New financial innovations like cryptocurrencies can be analyzed applying the equation of exchange in light of the mechanics of money creation under conditions of disequilibrium. Monetary disequilibrium may be promoted by policy that causes bottlenecks in financial markets.

Originality/value

Theory of monetary disequilibrium has broad implications for the development and regulation of financial markets. This theory has not been applied to the development of cryptocurrency markets.
Japanese guidelines for the management of pemphigoid (including epidermolysis bullosa acquisita)
Authors: Ujiie Hideyuki , Iwata Hiroaki , Yamagami Jun , Nakama Takekuni , Aoyama Yumi , Ikeda Shigaku , Ishii Norito , Iwatsuki Keiji , Kurosawa Michiko , Sawamura Daisuke , Tanikawa Akiko , Tsuruta Daisuke , Nishie Wataru , Fujimoto Wataru , Amagai Masayuki , Shimizu Hiroshi ,   Committee for Guidelines for the Management of Pemphigoid Diseases (Including Epidermolysis Bullosa Acquisita)
Published: October 2019

The pemphigoid group is a category of autoimmune subepidermal blistering diseases in which autoantibodies deposit linearly at the epidermal basement membrane zone (BMZ). The main subtypes of pemphigoid mediated by immunoglobulin G autoantibodies are bullous pemphigoid (BP), mucous membrane pemphigoid (MMP) and epidermolysis bullosa acquisita (EBA). To establish the first guidelines approved by the Japanese Dermatological Association for the management of pemphigoid diseases, the Committee for Guidelines for the Management of Pemphigoid Diseases (Including EBA) was founded as part of the Study Group for Rare Intractable Skin Diseases under the Ministry of Health, Labor and Welfare Research Project on Overcoming Intractable Diseases. These guidelines aim to provide current information for the management of BP, MMP and EBA in Japan. Based on evidence, the guidelines summarize the clinical and immunological manifestations, pathophysiologies, diagnostic criteria, disease severity determination criteria, treatment algorithms and treatment recommendations. Because of the rarity of these diseases, there are few clinical studies with a high degree of evidence, so several parts of these guidelines were established based on the opinions of the Committee. To further optimize these guidelines, periodic revision in line with the new evidence is necessary.
Review article: fungal alterations in inflammatory bowel diseases
Authors: Lam Siu , Zuo Tao , Ho Martin , Chan Francis K. L. , Chan Paul K. S. , Ng Siew C.
Published: October 2019

Background

Emerging data suggest that alterations in gut fungi may be associated with the pathogenesis of inflammatory bowel disease (IBD). In healthy individuals, gut commensal fungi act synergistically with other members of the microbiota to maintain homeostasis but their role in IBD is less clear.

Aim

To review the role of gut fungi and their trans‐kingdom interactions with bacteria in IBD

Methods

A literature search was conducted on Ovid and Pubmed to select relevant animal and human studies that have reported fungi and IBD.

Results

There is an increased total fungal load particularly of Candida and Malassezia species in the faeces and mucosa of Crohn's disease patients, and a lower fungal diversity in the faeces of ulcerative colitis patients. Caspase recruitment domain‐containing protein (CARD)‐9 polymorphism in Crohn's disease patients favours Malassezia colonisation that worsens gut inflammation. Diet high in carbohydrates increased the total abundance of Candida species, whereas protein‐rich diet had the opposite effect. Anti‐fungal therapies are mostly used to treat Candida albicans or Histoplasma capsulatum infections in IBD, whereas pilot studies of supplementing fungal probiotics Saccharomycopsis fibuligera, Saccharomyces boulardii and Saccharomyces cerevisiae CNCM I‐3856 strain showed therapeutic effects in IBD.

Conclusions

Gut fungi are altered in patients with Crohn's disease and ulcerative colitis. Modulation of the fungal microbiota can be considered as a therapeutic approach for IBD. Future research should focus on understanding how the fungal microbiota interacts with other components of the gut microbiota in association with the pathogenesis and development of IBD.
Insulin resistance: Relationship between indices during late gestation in dairy cows and effects on newborn metabolism
Authors: Hasegawa Rui , Iwase Izumi , Takagi Tomohiro , Kondo Moeri , Matsui Motozumi , Kawashima Chiho
Published: October 2019

To investigate the relationship between insulin resistance indices [“Revised quantitative insulin sensitivity check index” (RQUICKI; RQ), “Revised quantitative insulin sensitivity check index ‐ β‐hydroxybutyrate” (RQUICKIBHB; RQBHB), and “Homeostasis model assessment‐insulin resistance” (HOMA‐IR; HR)], and metabolic parameters in dams during late gestation, and their newborn calves. Blood was sampled twice weekly during the experimental period in 30 dry Holstein cows. In calves, blood sampling and body weight measurements were performed immediately after birth, and in 1‐week‐old male calves, liver and muscle biopsy samples were obtained for determining metabolic factor mRNA levels. RQ and RQBHB were negatively correlated with insulin, nonesterified fatty acid, BHB, and albumin and were positively correlated with leptin levels in blood during late gestation (p < .05). RQ, rather than RQBHB, reflected metabolism of dams, while stronger positive correlations were present between HR and blood insulin concentrations than other parameters, and calves of dams with high HR had low body weight, and high liver and muscle expression of growth hormone and insulin receptor mRNA (p < .05). RQ and HR of dams during late gestation could serve as indicators of dam metabolism and predictors of metabolism in newborn calves respectively.
Dynamic modeling of multivariate dimensions and their temporal relationships using latent processes: Application to Alzheimer's disease
Authors: Taddé Bachirou O. , Jacqmin‐Gadda Hélène , Dartigues Jean‐François , Commenges Daniel , Proust‐Lima Cécile
Published: October 2019

Alzheimer's disease gradually affects several components including the cerebral dimension with brain atrophies, the cognitive dimension with a decline in various functions, and the functional dimension with impairment in the daily living activities. Understanding how such dimensions interconnect is crucial for Alzheimer's disease research. However, it requires to simultaneously capture the dynamic and multidimensional aspects and to explore temporal relationships between dimensions. We propose an original dynamic structural model that accounts for all these features. The model defines dimensions as latent processes and combines a multivariate linear mixed model and a system of difference equations to model trajectories and temporal relationships between latent processes in finely discrete time. Dimensions are simultaneously related to their observed (possibly multivariate) markers through nonlinear equations of observation. Parameters are estimated in the maximum likelihood framework enjoying a closed form for the likelihood. We demonstrate in a simulation study that this dynamic model in discrete time benefits the same causal interpretation of temporal relationships as models defined in continuous time as long as the discretization step remains small. The model is then applied to the data of the Alzheimer's Disease Neuroimaging Initiative. Three longitudinal dimensions (cerebral anatomy, cognitive ability, and functional autonomy) measured by six markers are analyzed, and their temporal structure is contrasted between different clinical stages of Alzheimer's disease.
Isoprenaline protects intestinal stem cells from chemotherapy‐induced damage
Authors: Zeng Huihong , Li Huan , Yue Mengzhen , Fan Ying , Cheng Jiaoqi , Wu Xincheng , Xu Rui , Yang Wuping , Li Manjun , Tang Jiahui , Chen Hongping , Kuang Bohai , Fan Guangqin , Zhu Qingxian , Shao Lijian
Published: October 2019

Background and Purpose

Damage to intestinal epithelial cells and mucosa limits the effectiveness of several anti‐cancer chemotherapeutic agents but the underlying mechanism (s) remain unknown. Little is known of how enteric nervous system regulates proliferation, differentiation, impairment, and regeneration of intestinal stem cells. Here we have investigated the effects of isoprenaline on the damaged intestinal stem cells induced by chemotherapeutic treatments in mice.

Experimental Approach

The effects of inhibiting sympathetic and parasympathetic nerves on intestinal stem cells were examined in male C57BL/6J mice. Protection by isoprenaline of intestinal stem cells was assessed in the presence or absence of 5‐fluorouracil (5FU) or cisplatin. Cellular apoptosis, cell cycle, PI3K/Akt signalling, and NF‐κB signalling in intestinal stem cells were mechanistically evaluated.

Key Results

The sympathetic nerve inhibitor 6‐OHDA decreased the number and function of intestinal stem cells. 5FU or cisplatin treatment damaged both intestinal stem cells and sympathetic nerves. Notably, isoprenaline accelerated the recovery of intestinal stem cells after 5FU or cisplatin treatment. This protective effect of isoprenaline on damaged intestinal stem cells was mediated by β2‐adrenoceptors. The benefits of isoprenaline were mainly mediated by inhibiting cellular apoptosis induced by 5FU treatment, which might contribute to fine‐tuning regulating NF‐κB signalling pathway by isoprenaline administration.

Conclusions and Implications

Treatment with isoprenaline is a new approach to ameliorate the damage to intestinal stem cells following exposure to cancer chemotherapeutic agents.
The enhanced immunopharmacology of VIB4920, a novel Tn3 fusion protein and CD40L antagonist, and assessment of its safety profile in cynomolgus monkeys
Authors: Nicholson Simone M. , Casey Kerry A. , Gunsior Michele , Drabic Stacey , Iverson William , Cook Halie , Scott Stephen , O'Day Terry , Karanth Subramanya , Dixit Rakesh , Ryan Patricia C.
Published: October 2019

Background and Purpose

Inhibition of the T‐ and B‐cell interaction through the CD40/CD40 ligand (L) axis is a favourable approach for inflammatory disease treatment. Clinical studies of anti‐CD40L molecules in autoimmune diseases have met challenges because of thromboembolic events and adverse haemostasis. VIB4920 (formerly MEDI4920) is a novel CD40L antagonist and Tn3 fusion protein designed to prevent adverse haemostasis and immunopharmacology. We evaluated the pharmacokinetics, activity and toxicity of VIB4920 in monkeys.

Experimental Approach

Cynomolgus monkeys received i.v. or s.c. 5–300 mg·kg−1 VIB4920 or vehicle, once weekly for 1 month (Studies 1 and 2) or 28 weeks (Study 3). VIB4920 exposure and bioavailability were determined using pharmacokinetic analyses, and immune cell population changes via flow cytometry. Pharmacological activity was evaluated by measuring the animals' capacity to elicit an immune response to keyhole limpet haemocyanin (KLH) and tetanus toxoid (TT).

Key Results

VIB4920 demonstrated linear pharmacokinetics at multiple doses. Lymphocyte, monocyte, cytotoxic T‐cell and NK cell counts were not significantly different between treatment groups. B‐cell counts reduced dose‐dependently and the T‐cell dependent antibody response to KLH was suppressed by VIB4920 dose‐dependently. The recall response to TT was similar across treatment groups. No thromboembolic events or symptoms of immune system dysfunctionality were observed.

Conclusions and Implications

VIB4920 demonstrated an acceptable safety profile in monkeys. VIB4920 showed favourable pharmacokinetics, dose‐dependent inhibition of a neoantigen‐specific immune response and no adverse effects on immune function following long‐term use. Our data support the use of VIB4920 in clinical trials.
“If they misbehaved, we took a stick to discipline them”: Refugee mothers' struggles raising children in the United States
Authors: Kohli Hermeet K. , Fineran Susan
Published: October 2019

Although there are compelling examples of stress put upon refugee families, there is little systematic attention placed upon how the refugee women themselves view child‐rearing. In this exploratory research, refugee women's narratives concerning their understanding and perceptions of child‐rearing in the United States are studied. Seventeen refugee women raising children living in the Greater Portland region in Maine were interviewed. While resettling in the United States, the participants shared being overburdened by the loss of social structures that supported their parenting beliefs and strategies back home. They perpetually encounter cultural conflicts in the United States that result in a continuous process of contradictory interpretations and negotiations while rearing and disciplining children. Recommendations are provided for service providers working with this population. Professionals have to be cognizant of the hierarchical decision‐making and retributive strategies used by refugee families when disciplining children. Tools, that is, explaining, teaching, and rewarding children for coping with parenting challenges without resorting to punitive discipline methods can be introduced to refugee families. Professionals need to focus on providing refugee families with basic needs and addressing social and emotional challenges so that they can better integrate with the new communities as they rebuild their lives.
Collaboration and conversations with children in Child Welfare Services —Parents' viewpoint
Authors: Juul Randi , Husby Inger Sofie Dahlø
Published: October 2019

Collaboration and conversations are important in meeting vulnerable children's needs in the context of Child Welfare Services (CWS). Building on 10 qualitative interviews with parents of children in Norwegian Child Welfare Services, this paper discusses parents' views on collaboration between children and child welfare professionals. The parents stated that a constructive collaborative relationship depends on professionals' attitudes towards the child, their ability to connect with the child and their awareness of how the child's emotions and how the parents influence the child–professional relationship. A collaborative relationship is essential for child welfare professionals to meet the child's needs and to help improve relations between the child and the parents. The parents asked for more collaboration between children and child welfare professionals. The findings call for more discussion of child welfare workers' tasks and competence.
Availability of licensed cannabis businesses in relation to area deprivation in Washington state: A spatiotemporal analysis of cannabis business presence between 2014 and 2017
Authors: Amiri Solmaz , Monsivais Pablo , McDonell Michael G. , Amram Ofer
Published: October 2019

Introduction and Aims

In states where recreational use of cannabis has been legalised, increasing numbers of cannabis licensed cannabis businesses resulted in concerns about their potential social and health impacts. This study examined spatiotemporal variations in availability of cannabis licensed cannabis businesses (i.e. producers, processors and retailers) in relation to area deprivation in Washington state from 2014 to 2017.

Design and Methods

Data on licensed cannabis businesses were obtained from the Washington State Liquor and Cannabis Board. The number of licensed cannabis businesses was estimated for Washington's 1446 census tracts. Census tracts were stratified into tertiles based on the Singh's Area Deprivation Index showing socio‐economic characteristics of communities (least‐deprived, middle‐deprived and most‐deprived). The Integrated Nested Laplace Approximation approach allowed for the spatial and temporal characterisation of cannabis businesses, accounting for similarities based on neighbouring census tracts.

Results

The density of all licensed cannabis outlets increased over time. Most‐deprived areas have increased likelihood of licensed cannabis outlet density when compared to least‐deprived areas. No differences were observed in the likelihood of licensed cannabis outlet density in middle‐deprived areas when compared to least‐deprived areas.

Discussion and Conclusions

The results of this study showed disparity with respect to licensed cannabis outlet density in Washington state over time. The findings call for initiatives, policies and research that decrease disparities in cannabis outlet locations.
The Unfixed State of Unfixed Land
Authors: Sud Nikita
Published: October 2019

Land is unfixed. Qualitative research in India shows humans physically reconfiguring, legally redefining, politically relabelling and discursively re‐imagining land in growth‐ and investment‐led policies. The state is a key actor in the material and conceptual unfixing of land, and its re‐fixing to emerging developmental imaginations. But land is not just a territorial container for the implementation of policy. Rather, it routinely stretches the boundaries of state authority. In the fieldwork on which this article is based, unfixed, multi‐dimensional land emerges as contested access, social and political territory making, possession that goes beyond the legality of property, and more. As unfixed land extends beyond the boundaries and authority of the state, the state too is stretched in projects of land's unfixing and re‐fixing. This state is revealed as porous, and with a criss‐crossing of social relationships that draw out its institutional bounds into a world of moonlighting officials, revolving doors, and shadowy actors and transactions over unfixed land. The result of this co‐productive interaction is the unfixed state of unfixed land.
Aortic, common carotid and external iliac artery arterial wall stiffness parameters in horses: Inter‐day and inter‐observer and intra‐observer measurement variability
Authors: Vera L. , De Clercq D. , Paulussen E. , Van Steenkiste G. , Decloedt A. , Chiers K. , van Loon G.
Published: October 2019

Background

In human medicine, local and regional arterial wall stiffness (AWS) parameters are routinely used to assess the vascular health. In horses, information regarding reproducibility of ultrasonographically derived AWS parameters is lacking.

Objectives

To evaluate the inter‐day and inter‐observer and intra‐observer measurement variability of both local and regional AWS parameters in horses.

Study design

Experimental study.

Methods

In 10 healthy, adult Warmblood horses, B‐, M‐mode and pulsed‐wave Doppler ultrasound images were collected on two different days from aorta, cranial and caudal common carotid arteries and external iliac artery. Heart rate and noninvasive blood pressure were recorded simultaneously. From blinded data, diastolic and systolic vessel lumen areas and diameters were measured from B/M‐mode images and the velocity of the pressure wave was determined by pulsed‐wave Doppler spectra. From each horse, one examination was measured again by the same observer and by a second, independent observer. Local and regional AWS parameters were calculated and inter‐day and inter‐observer and intra‐observer measurement coefficient of variation (CV) were assessed.

Results

Low CV was found for both arterial diameter and lumen area measurements. Moderate to high CV was found for local AWS parameters, while regional AWS parameters had low CV.

Main limitations

The number of horses investigated was too low to obtain reference values. The inter‐operator variability was not evaluated.

Conclusions

Our results show good reproducibility of aortic, carotid and external iliac artery diameter and area measurements using both B‐ and M‐mode ultrasonography. Nevertheless, the variability of the derived local AWS parameters was relatively high. Therefore, local AWS parameters might be less suitable for follow‐up studies, although they might be useful for population studies. On the other hand, regional AWS parameters showed low CV, making them valuable for both follow‐up and population studies.