bluuebunny/crossref_metadata_2025_split huggingface dataset:
A laboratory demand optimisation project in primary care
Authors: Bucholc Magda , O’Kane Maurice , O’Hare Brendan , Mullan Ciaran , Cavanagh Paul , Ashe Siobhan , Wong-Lin KongFatt 
Published: January 2018

AbstractBackgroundThere is evidence of increasing use of laboratory tests with substantial variation between clinical teams which is difficult to justify on clinical grounds. The aim of this project was to assess the effect of a demand optimisation intervention on laboratory test requesting in primary care.MethodsThe intervention comprised educational initiatives, feedback to 55 individual practices on test request rates with ranking relative to other practices, and a small financial incentive for practices to engage and reflect on their test requesting activity. Data on test request numbers were collected from the laboratory databases for consecutive 12 month periods; pre‐intervention 2011-12, intervention 2012-13, 2013-14, 2014-15, and post-intervention 2015-16.ResultsThe intervention was associated with a 3.6% reduction in the mean number of profile test requests between baseline and 2015-16, although this was seen only in rural practices. In both rural and urban practices, there was a significant reduction in-between practice variability in request rates. The mean number of HbA1crequests increased from 1.9 to 3.0 per practice patient with diabetes. Variability in HbA1crequest rates increased from 23.8% to 36.6%. At all considered time points, test request rates and variability were higher in rural than in urban areas.ConclusionsThe intervention was associated with a reduction in both the volume and between practice variability of profile test requests, with differences noted between rural and urban practices. The increase in HbA1crequests may reflect a more appropriate rate of diabetes monitoring and also the adoption of HbA1cas a diagnostic test.Strengths & limitations of the studyWe assessed the effect of a laboratory demand optimisation intervention both on the value and between GP practice variability in laboratory test requesting.The changes in laboratory test requesting were separately evaluated for rural and urban GP practices.Other factors (GP practice organisation, characteristics of general practitioners) potentially affecting between practice differences in laboratory test ordering were not taken into account due to data unavailability.The demand management initiative was not accompanied by the cost-effectiveness analysis.The demand optimisation intervention was conducted in a Northern Ireland (NI) Western Health and Social Care Trust and the findings have not been independently replicated in any other NI trusts.
Type-2 CD8+T lymphocytes responsive to PGD2and LTE4in severe eosinophilic asthma
Authors: Hilvering Bart , Hinks Timothy SC , Stöger Linda , Marchi Emanuele , Salimi Maryam , Shrimanker Rahul , Liu Wei , Chen Wentao , Luo Jian , Go Simei , Powell Timothy , Cane Jennifer , Thulborn Samantha , Kurioka Ayako , Leng Tianqi , Matthews Jamie , Connolly Clare , Borg Catherine , Bafadhel Mona , Willberg Christian B , Ramasamy Adaikalavan , Djukanović Ratko , Ogg Graham , Pavord Ian D , Klenerman Paul , Xue Luzheng 
Published: January 2018

ABSTRACTThe functions andin vivoroles of type-2 CD8+T cells in humans have not been well defined and this cell type has been largely overlooked in models of disease. We investigated this in the context of severe asthma with persistent airway eosinophilia - a phenotype associated with high exacerbation risk and responsiveness to type-2 cytokine-targeted therapies. In two independent cohorts we show that, in contrast to Th2 cells, type-2 cytokine-secreting CD8+CRTH2+(Tc2) cells are enriched in blood and airways in severe eosinophilic asthma. Concentrations of prostaglandin D2(PGD2) and cysteinyl leukotriene E4(LTE4) are also increased in the airways of the same group of patients.In vitroPGD2and LTE4function synergistically to trigger Tc2 cell recruitment and activation in a TCR-independent manner. These lipids regulate diverse genes in Tc2 cells inducing type-2 cytokines and many other pro-inflammatory cytokines and chemokines which could contribute to eosinophilia. These findings are consistent with an important innate-like role for human Tc2 cells in severe eosinophilic asthma and suggest a potential target for therapeutic intervention in this and other diseases.
Engineering of a Polydisperse Small Heat-Shock Protein Reveals Conserved Motifs of Oligomer Plasticity
Authors: Mishra Sanjay , Chandler Shane A. , Williams Dewight , Claxton Derek P. , Koteiche Hanane A. , Stewart Phoebe L. , Benesch Justin L.P. , Mchaourab Hassane S. 
Published: January 2018

AbstractSmall heat-shock proteins (sHSP) are molecular chaperones that bind and sequester partially and globally unfolded states of their client proteins. Of paramount importance to their physiological roles is the assembly into large oligomers, which for mammalian sHSP are polydisperse and undergo subunit exchange. The flexibility and dynamic nature of these oligomers mediates functional regulation by phosphorylation and underpins the deleterious effects of disease-linked mutations. Previously, we discovered that the archaeal Hsp16.5, which natively forms ordered and symmetric 24-subunit oligomers, can be engineered to transition to an ordered and symmetric 48-subunit oligomer by insertion of a peptide from human HspB1 (Hsp27) at the junction of the N-terminal and α-crystallin domains. Here, we carried out a detailed analysis of the determinants of Hsp16.5 oligomeric plasticity by altering the sequence and length of the inserted peptide. Utilizing light scattering, blue native gel electrophoresis, native mass spectrometry and electron microscopy, we uncovered the existence of an array of oligomeric states (30 to 38 subunits) that can be populated as a consequence of different insertions. These oligomers are intermediate states on the assembly pathway of the 48-subunit oligomer as two of the variants can concurrently form 24-subunit or 30-38 subunit polydisperse oligomers. Polydisperse Hsp16.5 oligomers displayed higher affinity to a model client protein consistent with a general mechanism for recognition and binding that involves increased access of the hydrophobic N-terminal region. Our findings, which integrate structural and functional analyses from evolutionarily-distant sHSP, support a model wherein the modular architecture of these proteins encodes motifs of oligomer polydispersity, dissociation and expansion to achieve functional diversity and regulation.
Accurate detection of convergent amino-acid evolution with PCOC
Authors: Rey Carine , Guéguen Laurent , Sémon Marie , Boussau Bastien 
Published: January 2018

AbstractIn the history of life, some phenotypes have been acquired several times independently, through convergent evolution. Recently, lots of genome-scale studies have been devoted to identify nucleotides or amino acids that changed in a convergent manner when the convergent phenotypes evolved. These efforts have had mixed results, probably because of differences in the detection methods, and because of conceptual differences about the definition of a convergent substitution. Some methods contend that substitutions are convergent only if they occur on all branches where the phenotype changed towards the exact same state at a given nucleotide or amino acid position. Others are much looser in their requirements and define a convergent substitution as one that leads the site at which they occur to prefer a phylogeny in which species with the convergent phenotype group together. Here we suggest to look for convergent shifts in amino acid preferences instead of convergent substitutions to the exact same amino acid. We define as convergent shifts substitutions that occur on all branches where the phenotype changed and such that they correspond to a change in the type of amino acid preferred at this position. We implement the corresponding model into a method named PCOC. We show on simulations that PCOC better recovers convergent shifts than existing methods in terms of sensitivity and specificity. We test it on a plant protein alignment where convergent evolution has been studied in detail and find that our method recovers several previously identified convergent substitutions and proposes credible new candidates.
How the Central American Seaway and an ancient northern passage affected flatfish diversification
Authors: Byrne Lisa , Chapleau François , Aris-Brosou Stéphane 
Published: January 2018

AbstractWhile the natural history of flatfish has been debated for decades, the mode of diversification of this biologically and economically important group has never been elucidated. To address this question, we assembled the largest molecular data set to date, covering > 300 species (out of ca. 800 extant), from 13 of the 14 known families over nine genes, and employed relaxed molecular clocks to uncover their patterns of diversification. As the fossil record of flatfish is contentious, we used sister species distributed on both sides of the American continent to calibrate clock models based on the closure of the Central American Seaway (CAS), and on their current species range. We show that flatfish diversified in two bouts, as species that are today distributed around the Equator diverged during the closure of CAS, while those with a northern range diverged after this, hereby suggesting the existence of a post-CAS closure dispersal for these northern species, most likely along a trans-Arctic northern route, a hypothesis fully compatible with paleogeographic reconstructions.
A robust method for RNA extraction and purification from a single adult mouse tendon
Authors: Grinstein M , Dingwall HL , Shah RR , Capellini TD , Galloway JL 
Published: January 2018

AbstractBackgroundMechanistic understanding of tendon molecular and cellular biology is crucial towards furthering our abilities to design new therapies for tendon and ligament injuries and disease. Recent transcriptomic and epigenomic studies in the field have harnessed the power of mouse genetics to reveal new insights into tendon biology. However, many mouse studies pool tendon tissues or use amplification methods to perform RNA analysis, which can significantly increase the experimental costs and limit the ability to detect changes in expression of low copy transcripts.MethodsSingle Achilles tendons were harvested from uninjured, contralateral injured, and wild type mice between 3-5 months of age, and RNA was extracted. RNA Integrity Number (RIN) and concentration were determined, and RT-qPCR gene expression analysis was performed.ResultsAfter testing several RNA extraction approaches on single adult mouse Achilles tendons, we developed a protocol that was successful at obtaining high RIN and sufficient concentrations suitable for RNA analysis. We found that the RNA quality was sensitive to the time between tendon harvest and homogenization, and the RNA quality and concentration was dependent on the duration of homogenization. Using this method, we demonstrate that analysis of Scx gene expression in single mouse tendons reduces the biological variation caused by pooling tendons from multiple mice. We also show successful use of this approach to analyze Sox9 and Col1a2 gene expression changes in injured compared with uninjured control tendons.DiscussionOur work presents a robust, cost-effective, and straightforward method to extract high quality RNA from a single adult mouse Achilles tendon at sufficient amounts for RNA-seq and RT-qPCR. We show this can reduce biological variation and decrease the overall costs associated with experiments. This approach can also be applied to other skeletal tissues as well as precious human samples.
Mixing is required for uniform reconstitution of filter-dried protein antigens in a single-injection vaccine formulation
Authors: Thangsupanimitchai Napawan , Edwards Alexander D. 
Published: January 2018

AbstractAmbient temperature filter dried vaccine formulations have been proposed to simultaneously achieve thermostability and offer a ready-to-use immunisation device that combines reconstitution and injection. Vaccine concentration should be uniform at the point of injection, but the uniformity following direct reconstitution of filter-dried vaccines has not been reported. We present here a study of vaccine mixing and release following dissolution of filter-dried model protein and toxoid antigens within a single syringe, filter and needle unit. Release was better for filters made from glass than cellulose. Without additional mixing, uniformity was poor and only 41% of input protein was released from protein filter-dried onto glass fibre. In contrast, adding a simple glass bead and mixing by inversion, 100% release antigen solution was achieved, with uniform concentration at exit from the needle throughout a simulated injection. Adsorption onto alum adjuvant had no detectable effect on vaccine dissolution and mixing. The uniformity and yield of low doses of diphtheria and tetanus toxoid was also improved by mixing, albeit with a lower yield of 60-68%. We conclude that uniformity and mixing should be studied to ensure safety and efficacy of directly reconstituted filter-dried vaccine formulations.
The Promise and Perils of Crowdfunding: Between Corporate Finance and Consumer Contracts
Authors: Armour John , Enriques Luca 
Published: January 2018

Abstract‘Crowdfunding’ is a burgeoning phenomenon. Its still‐evolving status is reflected in diversity of contracting practices: for example, ‘equity’ crowdfunders invest in shares, whereas ‘reward’ crowdfunders get advance units of product. These practices occupy a hinterland between existing regimes of securities law and consumer contract law. Consumer protection law in the UK (but not the US) imposes mandatory terms that impede risk‐sharing in reward crowdfunding, whereas US (but not UK) securities law mandates expensive disclosures that hinder equity crowdfunding. This article suggests that while crowdfunding poses real risks for funders, the classical regulatory techniques of securities and consumer law provide an ineffective response. Yet, a review of rapidly‐developing market mechanisms suggests they may provide meaningful protection for funders. An initially permissive regulatory approach, open to learning from market developments yet with a credible threat of intervention should markets fail to protect consumers, is justified.
Frozen Corpses and Feuding Parents: Re JS (Disposal of Body)
Authors: Conway Heather 
Published: January 2018

AbstractIn October 2016, a dying teenager won the legal right to have her remains cryogenically frozen and stored indefinitely in an American clinic. The cryonics aspect was novel, posing questions around the legality of this particular method of corpse ‘disposal’ in the UK and the processes involved. More significantly, the case raises other substantive legal issues around the fate of the dead, including the status of funeral instructions under English law, and how courts adjudicate parental disputes over the funeral arrangements for a dead child.
Residues in the analyst of the patient's symbiotic connection at a somatic level: unrepresented states in the patient and analyst
Authors: Godsil Geraldine 
Published: January 2018

AbstractThis paper discusses the residues of a somatic countertransference that revealed its meaning several years after apparently successful analytic work had ended. Psychoanalytic and Jungian analytic ideas on primitive communication, dissociation and enactment are explored in the working through of a shared respiratory symptom between patient and analyst. Growth in the analyst was necessary so that the patient's communication at a somatic level could be understood. Bleger's concept that both the patient's and analyst's body are part of the setting was central in the working through.
The analyst's Rorschach: gateway to opening the dialectical field
Authors: Alexy William 
Published: January 2018

AbstractThe author offers an account of his evolving relationship with the Rorschach test which for over 20 years as a private practice psychologist, he used in his clinical practice with the intent of mining patients’ psyches for useful information about personality organization and functioning. Coinciding with having found himself on the homestretch of analytic training and during a time when he desired clarity on how Rorschach assessment and Jungian analysis could fruitfully merge, there was an unexpected shift in emphasis wherein the Rorschach suddenly became a method for looking at himself as well. This challenge to identify and integrate aspects of self hitherto neglected was found to enrich his clinical practice. An historical perspective on this experience is offered which highlights the enigmatic relationship that existed between Carl Jung and Hermann Rorschach. The proverbial question of ‘What might this be?’ has been asked when administering the Rorschach for nearly a century. From an analytic perspective, the question is more fully and meaningfully asked when the person doing the asking has also been willing to step in, look around, and take notice of what happens.
Disrupted narrative and narrative symbol
Authors: Vuletić Georgije 
Published: January 2018

AbstractIn this article a specific type of narrative, which often appears in analytic sessions, is discussed. It is characterized by a seemingly ordinary, everyday topic and by a peculiar disruption of the narrative flow. The threefold structure of this type of narrative is described, along with its main characteristics. One element of this type of narrative is very similar to symbolic content or complex symbolic structures, e.g. dreams, the sort of material that can be used for the purpose of interpretation. The similarities as well as the differences are elaborated in the article. Thanks to the observed general structure and ‘symbolic’ nature of some parts of the narrative, it is easy to notice some of the unconscious elements, which are not familiar to the patient's ego, and to make an interpretation. Because these elements are close to the threshold of consciousness, the patient willingly accepts an interpretation based on them. This is especially true for patients whose dominant function is thinking. A temporary, working name for this type of narrative is proposed in the article: ‘disrupted narrative’ − and for its disruptive part ‘narrative symbol’.
C. G. Jung and intuition: from the mindscape of the paranormal to the heart of psychology
Authors: Pilard Nathalie 
Published: January 2018

AbstractIntuition is central in the work, practice, and philosophical legacy of C. G. Jung. In this paper, I will first discuss the importance of intuition for Jung in the paradigm usually designated the ‘paranormal’. Jung was attracted to intuition as an extra‐ordinary gift or function in the traditional sense, and this is considered here in relation to his 1896‐1899 Zofingia Lectures and 1902 On the Psychology and Pathology of So‐called Occult Phenomena: A Psychiatric Study. A significant development then occurred in 1913, when esotericist intuitions were turned toward psychological use with Jung's Red Book. There, his personal and private use of intuition – and we know how extraordinarily intuitive he was – led Jung to fully incorporate intuition at the core of his psychology. Not only in his practice, in the crucial intuitive form of empathy, but as we will see, also at the very heart of his theory. In 1921, Jung wrote Psychological Types, where intuition became one – the first – of the four fundamental functions and types of the psyche next to thinking, feeling, and sensation. In 1921, Jung proved to the world in rational argument that intuition was no longer a psychologist's hobby for table turning, but the most significant function of the psyche.
Correlation of dynamic contrast‐enhanced MRI derived volume transfer constant with histological angiogenic markers in high‐grade gliomas
Authors: Di Ningning , Yao Chenjun , Cheng Wenna , Ren Yan , Qu Jianxun , Wang Bin , Yao Zhenwei 
Published: January 2018

AbstractIntroductionTo ascertain if the volume transfer constant (Ktrans) derived from T1 dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) correlates with the immunohistological markers of angiogenesis in high‐grade gliomas.MethodsFifty‐one image‐guided biopsy specimens in 34 patients with newly presenting high‐grade gliomas (grade III = 16; grade IV = 18) underwent preoperative imaging (conventional imaging and T1 DCE‐MRI). We correlated vascular endothelial growth factor (VEGF) expression and the microvessel density (MVD) of MRI‐guided biopsy specimens with the corresponding DCE‐derived Ktrans. Histological sections were stained with VEGF and CD34, and examined under light microscopy. These histological and molecular markers of angiogenesis were correlated with the Ktrans of the region of interest corresponding to the biopsy specimen.ResultsThe Ktrans showed a significant positive correlation with VEGF expression (ρ = 0.582, P = 0.001) but not with MVD stained with CD34 antibody (ρ = 0.328, P = 0.072).ConclusionThe Ktrans derived from DCE‐MRI can reflect the VEGF expression of high‐grade gliomas but not the MVD.
“Economic Policies Are the Best Social Policies”: West German Neoliberalism and the Housing Question After 1945
Authors: Haderer Margaret 
Published: January 2018

AbstractThis article challenges the widespread view that neoliberalism had become hegemonic in the late 20th century by zooming into a less well‐known variant of neoliberalism, German ordoliberalism, whose political ascendency dates back to the 1940s and 1950s. Through the lens of post‐WWII housing policies—a central field of political intervention after 1945—this article focuses on the remaking of social policies as neoliberal policies in West Germany, a remake that rendered the market economy a key source of political legitimacy of the newly emerging, liberal democracy.
How does dose impact on the severity of food‐induced allergic reactions, and can this improve risk assessment for allergenic foods?
Authors: Dubois A. E. J. , Turner P. J. , Hourihane J. , Ballmer‐Weber B. , Beyer K. , Chan C.‐H. , Gowland M. H. , O'Hagan S. , Regent L. , Remington B. , Schnadt S. , Stroheker T. , Crevel R. W. R. 
Published: January 2018

AbstractQuantitative risk assessment (QRA) for food allergens has made considerable progress in recent years, yet acceptability of its outcomes remains stymied because of the limited extent to which it has been possible to incorporate severity as a variable. Reaction severity, particularly following accidental exposure, depends on multiple factors, related to the allergen, the host and any treatments, which might be administered. Some of these factors are plausibly still unknown. Quantitative risk assessment shows that limiting exposure through control of dose reduces the rates of reactions in allergic populations, but its impact on the relative frequency of severe reactions at different doses is unclear. Food challenge studies suggest that the relationship between dose of allergenic food and reaction severity is complex even under relatively controlled conditions. Because of these complexities, epidemiological studies provide very limited insight into this aspect of the dose‐response relationship. Emerging data from single‐dose challenges suggest that graded food challenges may overestimate the rate of severe reactions. It may be necessary to generate new data (such as those from single‐dose challenges) to reliably identify the effect of dose on severity for use in QRA. Success will reduce uncertainty in the susceptible population and improve consumer choice.