The Dynamic Chain Event Graph

In this paper we develop a formal dynamic version of Chain Event Graphs (CEGs), a particularly expressive family of discrete graph- ical models. We demonstrate how this class links to semi-Markov models and provides a convenient generalization of the Dynamic Bayesian Network (DBN). In particular we develop a repeating time-slice Dynamic CEG providing a useful and simpler model in this family. We demonstrate how the Dynamic CEG’s graphical formulation exhibits asymmetric conditional independence statements and also how each model can be estimated in a closed form enabling fast model search over the class. The expressive power of this model class together with its estimation is illustrated throughout by a variety of examples that include the risk of childhood hospitalization and the efficacy of a flu vaccine

Microarray studies reveal novel genes associated with endocrine resistance in breast cancer

Background Endocrine resistance is a major hurdle in breast cancer management, and determining the underlying factors driving its growth and aggressive behaviour should vastly improve treatment. Methods Microarray technology (BD Atlas Plastic Human 12 K Microarrays; GeneSifter software), verified by PCR, western blotting and immunocytochemisty, was used to identify genes increased in acquired resistant models to tamoxifen (TamR) or faslodex (FasR) as potential predictive/prognostic markers and new therapeutic targets. Results Alongside known breast cancer genes (β-catenin, PEA3, vitronectin, CD44), two novel genes in endocrine resistance were revealed (the latter never previously described in breast cancer): a securin/cell cycle regulator Pituitary Tumour Transforming Gene-1 (PTTG1), and GDNF receptor-alpha 3 (GFRα3) reported to promote cell survival signalling via RET coreceptor. Altered levels of PTTG1, GFRα3, or their associated family members were observed in further endocrine resistant states, including an additional faslodex resistant model that has progressed to a highly-aggressive state (FasR-Lt) and XMCF-7 cells resistant to oestrogen deprivation. PTTG1 and GFRα3 induction were also implicated in limiting response to anti-EGFR agents currently in breast cancer trials, with GFRα3 ligand (artemin) largely overcoming drug response. mRNA studies in clinical disease revealed PTTG1 associated with lymph node spread, high tumour grade and proliferation, while GFRα3 was enriched in ER-negative tumours and those expressing EGFR, profiles implying roles in clinical resistance and aggressive tumour behaviour. Promisingly, PTTG1 or GFRα3 siRNA knockdown promoted cell kill and inhibited proliferation in the resistant models. Conclusion Cumulatively, these data indicate PTTG1 and GFRα3 may provide useful biomarkers, and perhaps clinically relevant therapeutic targets for multiple resistant states

Continuous flow mechanochemistry: reactive extrusion as an enabling technology in organic synthesis

Rapid and wide-ranging developments have established mechanochemistry as a powerful avenue in sustainable organic synthesis. This is primarily due to unique opportunities which have been offered in solvent-free - or highly solvent-minimised - reaction systems. Nevertheless, despite elegant advances in ball-milling technology, limitations in scale-up still remain. This tutorial review covers the first reports into the translation from "batch-mode" ball-milling to "flow-mode" reactive extrusion, using twin-screw extrusion

CSTX-1, a toxin from the venom of the hunting spider Cupiennius salei, is a selective blocker of L-type calcium channels in mammalian neurons

The inhibitor cystine-knot motif identified in the structure of CSTX-1 from Cupiennius salei venom suggests that this toxin may act as a blocker of ion channels. Whole-cell patch-clamp experiments performed on cockroach neurons revealed that CSTX-1 produced a slow voltage-independent block of both mid/low- (M-LVA) and high-voltage-activated (HVA) insect Cav channels. Since C. salei venom affects both insect as well as rodent species, we investigated whether Cav channel currents of rat neurons are also inhibited by CSTX-1. CSTX-1 blocked rat neuronal L-type, but no other types of HVA Cav channels, and failed to modulate LVA Cav channel currents. Using neuroendocrine GH3 and GH4 cells, CSTX-1 produced a rapid voltage-independent block of L-type Cav channel currents. The concentration-response curve was biphasic in GH4 neurons and the subnanomolar IC50 values were at least 1000-fold lower than in GH3 cells. L-type Cav channel currents of skeletal muscle myoballs and other voltage-gated ion currents of rat neurons, such as INa(v) or IK(v) were not affected by CSTX-1. The high potency and selectivity of CSTX-1 for a subset of L-type channels in mammalian neurons may enable the toxin to be used as a molecular tool for the investigation of this family of Cav channels. © 2007 Elsevier Ltd. All rights reserved

Omnivorousness in sport: The importance of social capital and networks

There has been for some time a significant and growing body of research around the relationship between sport and social capital. Similarly, within sociology there has been a corpus of work that has acknowledged the emergence of the omnivore–univore relationship. Surprisingly, relatively few studies examining sport and social capital have taken the omnivore–univore framework as a basis for understanding the relationship between sport and social capital. This gap in the sociology of sport literature and knowledge is rectified by this study that takes not Putnam, Coleman or Bourdieu, but Lin’s social network approach to social capital. The implications of this article are that researchers investigating sport and social capital need to understand more about how social networks and places for sport work to create social capital and, in particular, influence participating in sporting activities. The results indicate that social networks both facilitate and constrain sports participation; whilst family and friendship networks are central in active lifestyles, those who are less active have limited networks

Outcome measurement in functional neurological disorder: a systematic review and recommendations.

OBJECTIVES: We aimed to identify existing outcome measures for functional neurological disorder (FND), to inform the development of recommendations and to guide future research on FND outcomes. METHODS: A systematic review was conducted to identify existing FND-specific outcome measures and the most common measurement domains and measures in previous treatment studies. Searches of Embase, MEDLINE and PsycINFO were conducted between January 1965 and June 2019. The findings were discussed during two international meetings of the FND-Core Outcome Measures group. RESULTS: Five FND-specific measures were identified-three clinician-rated and two patient-rated-but their measurement properties have not been rigorously evaluated. No single measure was identified for use across the range of FND symptoms in adults. Across randomised controlled trials (k=40) and observational treatment studies (k=40), outcome measures most often assessed core FND symptom change. Other domains measured commonly were additional physical and psychological symptoms, life impact (ie, quality of life, disability and general functioning) and health economics/cost-utility (eg, healthcare resource use and quality-adjusted life years). CONCLUSIONS: There are few well-validated FND-specific outcome measures. Thus, at present, we recommend that existing outcome measures, known to be reliable, valid and responsive in FND or closely related populations, are used to capture key outcome domains. Increased consistency in outcome measurement will facilitate comparison of treatment effects across FND symptom types and treatment modalities. Future work needs to more rigorously validate outcome measures used in this population

Surgical Correction of Hallermann-Streiff Syndrome: A Case Report of Esotropia, Entropion, and Blepharoptosis

We report a case of surgical treatment for Hallermann-Streiff syndrome in a patient with ocular manifestations of esotropia, entropion, and blepharoptosis. A 54-year-old man visited Yeouido St. Mary's Hospital complaining of ocular discomfort due to cilia touching the corneas of both eyes for several years. He had a bird-like face, pinched nose, hypotrichosis of the scalp, mandibular hypoplasia with forward displacement of the temporomandibular joints, a small mouth, and proportional short stature. His ophthalmic features included sparse eyelashes and eyebrows, microphthalmia, nystagmus, lower lid entropion in the right eye, and upper lid entropion with blepharoptosis in both eyes. There was esodeviation of the eyeball of more than 100 prism diopters at near and distance, and there were limitations in ocular movement on lateral gaze. The capsulopalpebral fascia was repaired to treat the right lower lid entropion, but an additional Quickert suture was required to prevent recurrence. Blepharoplasty and levator palpebrae repair were performed for blepharoptosis and dermatochalasis. Three months after lid surgery, the right medial rectus muscle was recessed 7.5 mm, the left medial rectus was recessed 7.25 mm, and the left lateral rectus muscle was resected 8.0 mm

Methodological criteria for the assessment of moderators in systematic reviews of randomised controlled trials : a consensus study

Background: Current methodological guidelines provide advice about the assessment of sub-group analysis within RCTs, but do not specify explicit criteria for assessment. Our objective was to provide researchers with a set of criteria that will facilitate the grading of evidence for moderators, in systematic reviews. Method: We developed a set of criteria from methodological manuscripts (n = 18) using snowballing technique, and electronic database searches. Criteria were reviewed by an international Delphi panel (n = 21), comprising authors who have published methodological papers in this area, and researchers who have been active in the study of sub-group analysis in RCTs. We used the Research ANd Development/University of California Los Angeles appropriateness method to assess consensus on the quantitative data. Free responses were coded for consensus and disagreement. In a subsequent round additional criteria were extracted from the Cochrane Reviewers’ Handbook, and the process was repeated. Results: The recommendations are that meta-analysts report both confirmatory and exploratory findings for subgroups analysis. Confirmatory findings must only come from studies in which a specific theory/evidence based apriori statement is made. Exploratory findings may be used to inform future/subsequent trials. However, for inclusion in the meta-analysis of moderators, the following additional criteria should be applied to each study: Baseline factors should be measured prior to randomisation, measurement of baseline factors should be of adequate reliability and validity, and a specific test of the interaction between baseline factors and interventions must be presented. Conclusions: There is consensus from a group of 21 international experts that methodological criteria to assess moderators within systematic reviews of RCTs is both timely and necessary. The consensus from the experts resulted in five criteria divided into two groups when synthesising evidence: confirmatory findings to support hypotheses about moderators and exploratory findings to inform future research. These recommendations are discussed in reference to previous recommendations for evaluating and reporting moderator studies

The 'four principles of bioethics' as found in 13(th) century Muslim scholar Mawlana's teachings

BACKGROUND: There have been different ethical approaches to the issues in the history of philosophy. Two American philosophers Beachump and Childress formulated some ethical principles namely 'respect to autonomy', 'justice', 'beneficence' and 'non-maleficence'. These 'Four Principles' were presented by the authors as universal and applicable to any culture and society. Mawlana, a great figure in Sufi tradition, had written many books which not only guide people how to worship God to be close to Him, but also advise people how to lead a good life to enrich their personality, as well as to create a harmonious society and a peaceful world. METHODS: In this study we examined the major works of Mawlana to find out which of these 'Four Principles of Bioethics' exist in Mawlana's ethical understanding. RESULTS: We have found in our study that all these principles exist in Mawlana's writings and philosophy in one form or another. CONCLUSIONS: We have concluded that, further to Beachump and Childress' claim that these principles are universal and applicable to any culture and society, these principles have always existed in different moral traditions in different ways, of which Mawlana's teaching might be presented as a good example