The Prime Diabetes Model: Novel Methods for Estimating Long-Term Clinical and Cost Outcomes in Type 1 Diabetes Mellitus

Background

Recent publications describing long-term follow-up from landmark trials and diabetes registries represent an opportunity to revisit modeling options in type 1 diabetes mellitus (T1DM).

Survey of life support training in teachers and provision of automated external defibrillators in secondary schools in South Wales

BackgroundSudden cardiac death in young people accounts for about 45 deaths per year in Wales. Early intervention with defibrillation improves survival for cardiac arrest. A recent intervention providing an automated external defibrillator (AED) to every high school in New York state, USA, eliminated sudden cardiac death in young people under 19 years over a 2-year period. We conducted a postal survey to establish whether secondary schoolteachers in South Wales had life support training and access to an AED.MethodsAll physical education departments in South Wales secondary schools (n=158, identified from Welsh Audit Office data) were sent postal questionnaires in May, 2014. Teachers were asked to provide information including the level of life support training and access to an AED. Completed questionnaires returned within 14 days were included in the study.FindingsResponses were received from 35 schools (22%). Responses are representative of 2133 teachers who are responsible for 30 000 pupils aged 11–18 years. 200 teachers (9·6%) reported having in-date life support training and a further 21 (1·0%) had training that included use of an AED. Ten schools had an AED on site with a further two that had AEDs located at an adjacent leisure centre. Three of the schools with AEDs had no trained staff (odds ratio 1·04, 95% CI 0·58–1·90, p=0·89). 73% of the respondents (115/158) agreed that life support training should be a mandatory part of training.InterpretationThe results suggest that only a small number of teachers in South Wales have life support training and access to an AED, and yet most teachers questioned expressed a desire to be trained in life support and to have access to an AED. Limitations to this study include the low response rate, which could reflect an inherent bias in the methodology whereby only interested teachers or schools with AEDs on site replied to the survey. These initial findings warrant further investigation at a national level, which would include a feasibility study exploring the implementation of a nationwide AED provision and training programme in schools.FundingNone.     

A stromal cell free culture system generates mouse pro‐T cells that can reconstitute T‐cell compartments in vivo

T‐cell lymphopenia following BM transplantation or diseases such as AIDS result in immunodeficiency. Novel approaches to ameliorate this situation are urgently required. Herein, we describe a novel stromal cell free culture system in which Lineage^?Sca1⁺c‐kit⁺ BM hematopoietic progenitors very efficiently differentiate into pro‐T cells. This culture system consists of plate‐bound Delta‐like 4 Notch ligand and the cytokines SCF and IL‐7. The pro‐T cells developing in these cultures express CD25, CD117, and partially CD44; express cytoplasmic CD3ε; and have their TCRβ locus partially D–J rearranged. They could be expanded for over 3 months and used to reconstitute the T‐cell compartments of sublethally irradiated T‐cell‐deficient CD3ε^?/? mice or lethally irradiated WT mice. Pro‐T cells generated in this system could partially correct the T‐cell lymphopenia of pre‐Tα^?/? mice. However, reconstituted CD3ε^?/? mice suffered from a wasting disease that was prevented by co‐injection of purified CD4⁺ CD25^high WT Treg cells. In a T‐cell‐sufficient or T‐lymphopenic setting, the development of disease was not observed. Thus, this in vitro culture system represents a powerful tool to generate large numbers of pro‐T cells for transplantation and possibly with clinical applications.     

Evaluation of the quality and accuracy of information regarding aromatase inhibitors available on the internet

Abstract:  The internet is commonly used by patients to access medical information, particularly where new treatments become available and are highlighted in the press. There is however, no regulation of the quality or accuracy of the information presented on web sites. The aim of this study was to evaluate the quality and accuracy of the information concerning the aromatase inhibitors (AIs). The three most popular search engines: Google, Yahoo, and MSN were utilized. The top ten "hits" for the generic and proprietary names of each AIs: anastrozole (Arimidex), exemestane (Aromasin), and letrozole (Femara) were evaluated using a 12-point score by a single assessor. The accuracy of the information provided was compared with the National Institute for Health and Clinical Excellence guidelines. The mean score for the 180 web sites was only 6.13 out of 12 (0–11). If we consider a score of 9 or more out of 12 (≥75%) for a web site to represent good quality information, then 51 (28%) of pages scored well. Google was slightly better than Yahoo and MSN; with the highest percentage of web sites scoring well. In evaluating hits according to type of web sites, 50 (28%) were charity web sites and 30 (17%) were drug company web sites and both groups scored significantly higher than the overall mean (charity p = 0.014, drug company p = 0.001). Only 2 of 180 hits gave accurate statistical evidence regarding the benefits of AIs over tamoxifen. We have found that the quality and accuracy of information concerning AIs provided on the Internet is poor and patients using it are unlikely to find accurate information. It is therefore our duty as healthcare providers to guide patients, so as to avoid them from being overwhelmed by irrelevant and conflicting information.     

Versatility and nuances of the architecture of haematopoiesis - Implications for the nature of leukaemia

For many years there was a widely accepted picture of how a haematopoietic stem cell (HSC) gives rise to the multiple types of blood and immune cells. This described the general nature of stem and progenitor cells and the pathways of cell development. Recent years have seen many attempts to re-draw the map of haematopoiesis. These have become increasingly complex, and they often envisage multiples routes to some cell types. The ‘established’ view that self-renewal in haematopoiesis only occurs in HSCs has been challenged by the recognition of self-renewing HSC-derived progenitor cells that display at least some fate restriction. This evolution of how normal haematopoiesis is viewed has inevitable implications for understanding the origins, disease progression and classification of the leukaemias. In essence, some progenitor cells are now seen as possessing a larger repertoire of routes to end-fates than was previously thought. This leads one to ask whether leukaemia stem cells are equally or less versatile than their normal counterparts?     

Is susceptibility to perceptual migration and fusion modality-specific or multimodal?

A previous paper reported high susceptibility to spatial migration (allochiria) of tactile stimuli in about 25% of healthy individuals (High Error subjects). When synchronous stimuli touched the two hands, if the unattended stimulus was temporally modulated when the attended one was not (and was thus more salient than the latter), it "migrated" to and fused with or replaced the stimulus on the attended hand. When subjects rated similarity of the attended stimulus accompanied by a distractor to each stimulus alone, scaling distributions tested against a sampling model showed most High Error subjects experienced fused stimuli, others experienced replacement and Low Error subjects experienced neither. We argued that these migrations are equivalent to allochiria and that this underlies neglect and extinction. This study assessed whether the individual difference is modality-specific or not. In auditory and visual equivalents of the tactile rating experiment, the difference between High and Low Error subjects was replicated in audition, but no migration occurred in vision. However, when two words were briefly presented visually before a mask with cued report of one, letter migrations to equivalent locations did occur and the individual difference was reproduced. This constitutes the first report of individual differences in auditory fusion and visual letter migration. Migration occurred in egocentric coordinates but apparently preserved structural homology. Different migration rates between the modalities paralleled relative salience of the unattended to the attended stimulus. The multimodality of the individual difference suggests that its source is supramodal, in deficient binding of perceptual content to location.     

Groupwise surface correspondence by optimization: representation and regularization

Groupwise optimization of correspondence across a set of unlabelled examples of shapes or images is a well-established technique that has been shown to produce quantitatively better models than other approaches. However, the computational cost of the optimization is high, leading to long convergence times. In this paper, we show how topologically non-trivial shapes can be mapped to regular grids, hence represented in terms of vector-valued functions defined on these grids (the shape image representation). This leads to an initial reduction in computational complexity. We also consider the question of regularization, and show that by borrowing ideas from image registration, it is possible to build a non-parametric, fluid regularizer for shapes, without losing the computational gain made by the use of shape images. We show that this non-parametric regularization leads to a further considerable gain, when compared to parametric regularization methods. Quantitative evaluation is performed on biological datasets, and shown to yield a substantial decrease in convergence time, with no loss of model quality.