Setting up a Support Group for Children, Adolescents and their Well Carers who have a Significant Adult with a Life-Threatening Illness

St Richard’s Hospice provides care and support for adults with a life-threatening illness and their families. As part of our work we often encounter children and adolescents who are facing the loss of a significant adult. Whereas in the past we have supported these children and young people primarily through one-to-one interactions after the adult has died, the expansion of our facilities has recently enabled us to provide an increasing degree of pre-death support, including the launch of a pre-death Child and Family Support Group. This article reflects on the benefits and challenges of setting up and running such a group and the journey we have gone through so far. It is our hope that by sharing our experiences we can demonstrate some of the benefits of group work for children and adolescents facing the loss of a significant adult and encourage others in the worldwide palliative care community who are considering running or are already providing such a service

A Modular Order-sorted Equational Generalization Algorithm

Generalization, also called anti-unification, is the dual of unification. Given terms t and t , a generalizer is a term t of which t and t are substitution instances. The dual of a most general unifier (mgu) is that of least general generalizer (lgg). In this work, we extend the known untyped generalization algorithm to, first, an order-sorted typed setting with sorts, subsorts, and subtype polymorphism; second, we extend it to work modulo equational theories, where function symbols can obey any combination of associativity, commutativity, and identity axioms (including the empty set of such axioms); and third, to the combination of both, which results in a modular, order-sorted equational generalization algorithm. Unlike the untyped case, there is in general no single lgg in our framework, due to order-sortedness or to the equational axioms. Instead, there is a finite, minimal and complete set of lggs, so that any other generalizer has at least one of them as an instance. Our generalization algorithms are expressed by means of inference systems for which we give proofs of correctness. This opens up new applications to partial evaluation, program synthesis, and theorem proving for typed equational reasoning systems and typed rulebased languages such as ASF+SDF, Elan, OBJ, Cafe-OBJ, and Maude. © 2014 Elsevier Inc. All rights reserved. 1.M. Alpuente, S. Escobar, and J. Espert have been partially supported by the EU (FEDER) and the Spanish MEC/MICINN under grant TIN 2010-21062-C02-02, and by Generalitat Valenciana PROMETEO2011/052. J. Meseguer has been supported by NSF Grants CNS 09-04749, and CCF 09-05584.Alpuente Frasnedo, M.; Escobar Román, S.; Espert Real, J.; Meseguer, J. (2014). A Modular Order-sorted Equational Generalization Algorithm. Information and Computation. 235:98-136. https://doi.org/10.1016/j.ic.2014.01.006S9813623

Symmetries in world geometry and adaptive system behaviour

. We characterise aspects of our worlds (great and small) in formalisms that exhibit symmetry; indeed symmetry is seen as a fundamental aspect of any physical theory. These symmetries necessarily have an impact on the way systems exhibit reactive behaviour in a given world for a symmetry determines an equivalence between states making it appropriate for an reactive system to respond identically to equivalent states. We develop the concept of a General Transfer Function (GTF) considered as a building block for reactive systems, dene the concept of full symmetry operator acting on a GTF, and show how such symmetries induce a quotient structure which simplies the process of building an invertible domain model for control. 1 Introduction This paper explores the relationship between symmetries of the world and symmetries of the (generalised) transfer functions which are used to characterise the response of a reactive system. It is written from the perspective of Articial Inte..

HSV-1 amplicons; a non-integrating, high transgene capacity tool for the generation and differentiation of induced pluripotent stem cells

Induced pluripotent stem (iPS) cells are valuable for generating patient-specific disease models. Many reprogramming systems have been developed however some technological concerns remain including insertional mutagenesis caused by integrating viruses, low efficiency and low transgene capacity. Herpes simplex virus type-1 (HSV-1) amplicons address the main limitations of current reprogramming methods as they are non-integrating and have a large transgene capacity of 150 Kb. In addition HSV-1 amplicons have a high transduction efficiency in both primary fibroblasts and iPS cells. We have developed three sets of HSV-1 amplicons to reprogram fibroblasts to iPS cells, directly differentiate fibroblasts to dopaminergic neurons and aid dopaminergic neuron differentiation from iPS cells. 1) We constructed and characterised a set of HSV-1 reprogramming amplicons, which express the reprogramming factors Oct-4, Sox-2, Klf-4, C-Myc, Nanog and Lin28. These vectors were capable of generating partially reprogrammed colonies as confirmed by RT-PCR analysis of pluripotency factors. We were unable to generate fully reprogrammed colonies and our results suggest that this is due to an induction of the p53 pathway. 2) We constructed an HSV-1 direct differentiation amplicon containing the polycistronic cassette Mash-1, Nurr-1 and Lmx1a. All elements were functional however we were unable to generate dopaminergic neurons. 3) We constructed and characterised a set of HSV-1 neuronal differentiation amplicons expressing the neuronal transcription factors Nurr-1, Lmx1a, FoxA2 and PitX3. We employed a 96 well differentiation protocol and transduced the differentiating cultures with our neuronal amplicons to try and improve dopaminergic neuron efficiency. Transduction at early time points in the protocol resulted in a significant increase in TH positive neurons.</p

HSV-1 amplicons; a non-integrating, high transgene capacity tool for the generation and differentiation of induced pluripotent stem cells

Induced pluripotent stem (iPS) cells are valuable for generating patient-specific disease models. Many reprogramming systems have been developed however some technological concerns remain including insertional mutagenesis caused by integrating viruses, low efficiency and low transgene capacity. Herpes simplex virus type-1 (HSV-1) amplicons address the main limitations of current reprogramming methods as they are non-integrating and have a large transgene capacity of 150 Kb. In addition HSV-1 amplicons have a high transduction efficiency in both primary fibroblasts and iPS cells. We have developed three sets of HSV-1 amplicons to reprogram fibroblasts to iPS cells, directly differentiate fibroblasts to dopaminergic neurons and aid dopaminergic neuron differentiation from iPS cells. 1) We constructed and characterised a set of HSV-1 reprogramming amplicons, which express the reprogramming factors Oct-4, Sox-2, Klf-4, C-Myc, Nanog and Lin28. These vectors were capable of generating partially reprogrammed colonies as confirmed by RT-PCR analysis of pluripotency factors. We were unable to generate fully reprogrammed colonies and our results suggest that this is due to an induction of the p53 pathway. 2) We constructed an HSV-1 direct differentiation amplicon containing the polycistronic cassette Mash-1, Nurr-1 and Lmx1a. All elements were functional however we were unable to generate dopaminergic neurons. 3) We constructed and characterised a set of HSV-1 neuronal differentiation amplicons expressing the neuronal transcription factors Nurr-1, Lmx1a, FoxA2 and PitX3. We employed a 96 well differentiation protocol and transduced the differentiating cultures with our neuronal amplicons to try and improve dopaminergic neuron efficiency. Transduction at early time points in the protocol resulted in a significant increase in TH positive neurons.</p

Functional characterisation of microRNAs encoded by avian herpesviruses

MicroRNAs (miRNAs) have now been identified in a vast array of organisms and a great deal of research has been carried out to elucidate the role they play. The dysregulation of miRNA expression has been implicated in a number of disease states and their importance has been highlighted by the beginning of their utilisation as therapeutics. The focus of this study was to identify the role played by miRNAs encoded by the Marek’s disease vaccine viruses, Marek’s disease virus serotype 2 (MDV-2) and Herpesvirus of turkeys (HVT). In order to better understand the functions of these miRNAs we wanted to identify their targets within the host cell. Using a combination of bioinformatic and biochemical approaches we were able to build up a library of potential targets. Three viral miRNA targets; AKT3, RAP1A and DEK, were further validated using dual-luciferase assays to highlight the exact site of miRNA targeting, and western blots to demonstrate an effect of miRNA targeting on protein abundance. An attempt at using label-free proteomics to observe the viral miRNA mediated changes in the host proteome is also described, however this proved to be unsuccessful. Additionally the function of one particular MDV-2 miRNA, mdv2-miR-M21, was explored in more detail, describing its role as a potential ortholog of the host miRNA; gga-miR-29b. By using the observation that the viral miRNA contained an identical 'seed' region to the host miRNA, we were able to use the data collected from existing studies on miR-29b to search for targets of mdv2-miR-M21. We demonstrated that mdv2-miR-M21 targeted DNMT3B, crucial for epigenetic modification of the genome. The final part of this study aimed to understand the wider context the viral miRNAs played in the viral biology and protective ability of the vaccine viruses. The miRNAs were deleted from the viruses, and then the miRNA-deletion viruses were used to vaccinate birds before challenge with the oncogenic Marek's disease virus serotype 1 (MDV-1), survival rates to the 'wild-type' MDV-2 and HVT vaccine viruses were then compared.</p