The genetics of developmental disorders

Children with developmental disorders often have complex health needs and require frequent input from many different paediatric services. Genomic technologies have revolutionised how these disorders are diagnosed, and have the real potential to transform the management of previously intractable paediatric conditions. For paediatricians to fully harness these benefits for our patients, and to work productively with our clinical genetics colleagues within the multi-disciplinary team, we must be genomically literate and aware of the technical and ethical challenges. In this review article, we will summarise the current understanding of the genetic architecture of developmental disorders; discuss the different types of genetic tests currently available, their strengths and limitations in clinical practice; and discuss the challenges and future opportunities in paediatric genomic medicine

Surveillance of heat-related illness in small animals presenting to veterinary practices in the UK between 2013-2018

Background: Heat-related illness (HRI) can affect all companion animals and is likely to become more common as global temperatures rise. The misconception that HRI is primarily a result of dogs being trapped in hot cars, highlights a lack of awareness of HRI risk factors within the UK companion animal population. Aim: This project aimed to review all species of small animal presentations of HRI to UK veterinary practices participating in the Small Animal Veterinary Surveillance Network (SAVSNET), describe the inciting triggers and seasonality of HRI events, and review the clinical grade of canine patients presenting with HRI. Methods: Electronic consultation records were submitted by volunteer veterinary practices across Great Britain to SAVSNET. Cases were defined as animals presented for consultation with strong evidence of current, or recent heat induced illness during the study period (2013-2018). Results: The HRI cases included 146 dogs, 16 cats, eight guinea pigs, three rabbits and one ferret. Of the 118 HRI cases with a recorded trigger, exercise was the primary trigger for dogs presenting (73.5%); seven (6.9%) canine HRI events followed vehicular confinement. Environmental HRI was recorded as a trigger for the remaining dogs (19.6%), and for all cats, guinea pigs, rabbits and the ferret. Brachycephalic breeds comprised 21.2% of canine HRI cases, and all rabbits were brachycephalic breeds. Dogs presented for HRI between April and October, with 42.5% during July, typically the UK’s hottest month of the year. Cats with HRI were presented between May and September, with 75.0% during June and July. The smaller companion species - ferrets, rabbits and guinea pigs – were presented during the UK’s summer months June to August. Conclusion: This study highlights the risk of HRI to all pet animals during the UK’s warmer summer months (June to August). The findings support previous claims that exercise is the most common trigger of HRI in dogs, whilst environmental HRI (a hot ambient temperature) accounted for all HRI events in cats, rabbits, guinea pigs and ferrets. Both brachycephalic dogs and rabbits were overrepresented, adding further evidence that owners of these animals should be particularly vigilant for HRI during hot weather

Differential genomic imprinting regulates paracrine and autocrine roles of IGF2 in mouse adult neurogenesis.

Genomic imprinting is implicated in the control of gene dosage in neurogenic niches. Here we address the importance of Igf2 imprinting for murine adult neurogenesis in the subventricular zone (SVZ) and in the subgranular zone (SGZ) of the hippocampus in vivo. In the SVZ, paracrine IGF2 is a cerebrospinal fluid and endothelial-derived neurogenic factor requiring biallelic expression, with mutants having reduced activation of the stem cell pool and impaired olfactory bulb neurogenesis. In contrast, Igf2 is imprinted in the hippocampus acting as an autocrine factor expressed in neural stem cells (NSCs) solely from the paternal allele. Conditional mutagenesis of Igf2 in blood vessels confirms that endothelial-derived IGF2 contributes to NSC maintenance in SVZ but not in the SGZ, and that this is regulated by the biallelic expression of IGF2 in the vascular compartment. Our findings indicate that a regulatory decision to imprint or not is a functionally important mechanism of transcriptional dosage control in adult neurogenesis.This work was supported by grants from Ministerio de Economía y Competitividad (SAF2012-40107), Generalitat Valenciana (Programa ACOMP2014-258) and Fundación BBVA to SRF and grants from the MRC, Wellcome Trust and EU FP7 Ingenium Training Network to AFS. AW and TRM were supported by the Association for International Cancer Research and Medical Research Council, UK.SRF was a recipient of a Herchel-Smith fellowship and currently is a Ramón y Cajal investigator. ADM is funded by a Spanish FPU fellowship program of the Ministerio de Educación, Cultura y Deporte. AR was from the Erasmus Placement Program.This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/ncomms926

Prescribing practices of primary-care veterinary practitioners in dogs diagnosed with bacterial pyoderma

Concern has been raised regarding the potential contributions of veterinary antimicrobial use to increasing levels of resistance in bacteria critically important to human health. Canine pyoderma is a frequent, often recurrent diagnosis in pet dogs, usually attributable to secondary bacterial infection of the skin. Lesions can range in severity based on the location, total area and depth of tissue affected and antimicrobial therapy is recommended for resolution. This study aimed to describe patient signalment, disease characteristics and treatment prescribed in a large number of UK, primary-care canine pyoderma cases and to estimate pyoderma prevalence in the UK vet-visiting canine population

Light hadron, Charmonium(-like) and Bottomonium(-like) states

Hadron physics represents the study of strongly interacting matter in all its manifestations and the understanding of its properties and interactions. The interest on this field has been revitalized by the discovery of new light hadrons, charmonium- and bottomonium-like states. I review the most recent experimental results from different experiments.Comment: Presented at Lepton-Photon 2011, Mumbai, India; 21 pages, 18 figures; add more references; some correctio

Increasing generality in machine learning through procedural content generation

Procedural Content Generation (PCG) refers to the practice, in videogames and other games, of generating content such as levels, quests, or characters algorithmically. Motivated by the need to make games replayable, as well as to reduce authoring burden, limit storage space requirements, and enable particular aesthetics, a large number of PCG methods have been devised by game developers. Additionally, researchers have explored adapting methods from machine learning, optimization, and constraint solving to PCG problems. Games have been widely used in AI research since the inception of the field, and in recent years have been used to develop and benchmark new machine learning algorithms. Through this practice, it has become more apparent that these algorithms are susceptible to overfitting. Often, an algorithm will not learn a general policy, but instead a policy that will only work for a particular version of a particular task with particular initial parameters. In response, researchers have begun exploring randomization of problem parameters to counteract such overfitting and to allow trained policies to more easily transfer from one environment to another, such as from a simulated robot to a robot in the real world. Here we review the large amount of existing work on PCG, which we believe has an important role to play in increasing the generality of machine learning methods. The main goal here is to present RL/AI with new tools from the PCG toolbox, and its secondary goal is to explain to game developers and researchers a way in which their work is relevant to AI research

Developing a Professional Studies Curriculum to Support Veterinary Professional Identity Formation

Professional studies teaching in medical and veterinary education is undergoing a period of change. Traditional approaches, aiming to teach students professional values and behaviors, are being enhanced by curricula designed to support students' professional identity formation. This development offers the potential for improving student engagement and graduates' mental well-being. The veterinary professional identity associated with emotional resilience and success in practice incorporates complexity in professional decision making and the importance of context on behaviors and actions. The veterinarian must make decisions that balance the sometimes conflicting needs of patient, clients, veterinarian, and practice; their subsequent actions are influenced by environmental challenges such as financial limitations, or stress and fatigue caused by a heavy workload. This article aims to describe how curricula can be designed to support the development of such an identity in students. We will review relevant literature from medical education and the veterinary profession to describe current best practices for supporting professional identity formation, and then present the application of these principles using the curriculum at the Royal Veterinary College (RVC) as a case study. Design of a “best practice” curriculum includes sequential development of complex thinking rather than notions of a single best solution to a problem. It requires managing a hidden curriculum that tends to reinforce a professional identity conceived solely on clinical diagnosis and treatment. It includes exposure to veterinary professionals with different sets of professional priorities, and those who work in different environments. It also includes the contextualization of taught content through reflection on workplace learning opportunities

P2X receptor-mediated purinergic sensory pathways to the spinal cord dorsal horn

P2X receptors are expressed on different functional groups of primary afferent fibers. P2X receptor-mediated sensory inputs can be either innocuous or nociceptive, depending on which dorsal horn regions receive these inputs. We provide a brief review of P2X receptor-mediated purinergic sensory pathways to different regions in the dorsal horn. These P2X purinergic pathways are identified in normal animals, which provides insights into their physiological functions. Future studies on P2X purinergic pathways in animal models of pathological conditions may provide insights on how P2X receptors play a role in pathological pain states