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Nazneen Rahman and colleagues identify inactivating germline mutations in the gene encoding the transcriptional repressor REST in familial and non-familial cases of Wilms tumor. The mutations cluster in the DNA-binding domain of REST and compromise REST transcriptional repression. Wilms tumor is the most common childhood renal cancer 1 . To identify mutations that predispose to Wilms tumor, we are conducting exome sequencing studies. Here we describe 11 different inactivating mutations in the REST gene (encoding RE1-silencing transcription factor) in four familial Wilms tumor pedigrees and nine non-familial cases. Notably, no similar mutations were identified in the ICR1000 control series 2 (13/558 versus 0/993; P < 0.0001) or in the ExAC series (13/558 versus 0/61,312; P < 0.0001). We identified a second mutational event in two tumors, suggesting that REST may act as a tumor-suppressor gene in Wilms tumor pathogenesis. REST is a zinc-finger transcription factor that functions in cellular differentiation and embryonic development 3 , 4 . Notably, ten of 11 mutations clustered within the portion of REST encoding the DNA-binding domain, and functional analyses showed that these mutations compromise REST transcriptional repression. These data establish REST as a Wilms tumor predisposition gene accounting for ∼2% of Wilms tumor.

BackgroundPresently, 8–10% of children and adolescents diagnosed with cancer have an underlying cancer predisposition syndrome, however the true figure may be higher. Family history alone identifies <4% of such patients and is therefore not sufficient in isolation as de novo mutations also occur. It is important to identify patients with cancer predisposition syndromes to guide further screening and tailor long term follow up and surveillance programmes. In addition, such information may help counsel family members on cancer risk. At present we believe we are under-referring patients for genetic cancer predisposition testing. The Royal Marsden Hospital is piloting a new system of identifying childhood and adolescent cancer patients for genetic screening.AimTo document how many patients at Our Lady’s Children’s Hospital, Crumlin, relevant to their specific cancer diagnosis, may benefit from genetic referral to identify those who may have an underlying cancer predisposition syndromeMethodsRetrospective review of all patients diagnosed with cancer in OLCHC between 01/01/2017 – 31/12/17.Using the Royal Marsden Hospital ‘Stop-light’ system relative to the patient’s diagnosis, patients who have a diagnosis labelled as:Red - automatically eligible for genetic referralYellow – may benefit from referralGreen – do not require referralResultsThere were 160 patients diagnosed in the period 01/01/2017 – 31/12/2017. Of these, 6 were excluded because of a pre-cancerous, rather than cancer, diagnosis: aplastic anaemia, transient abnormal myelopoiesis, post-transplant lymphoproliferative disorder and Fanconi anaemia. Of the remaining 154 patients diagnosed with cancer, 88 (57.1%) were classified as ‘green’ according to the Royal Marsden Hospital ‘Stop-light’ system. 48 (31.2%) were classified as ‘orange’ and 18 (11.7%) were classified as red, qualifying for automatic referral to clinical genetics.ConclusionsA significant proportion of patients diagnosed with cancer in OLCHC may benefit from referral to clinical genetics and screening for underlying cancer predisposition syndromes.

Scurvy is a disease that is rarely encountered in modern medicine. A condition that was classically associated with sailors, its incidence has decreased dramatically since the discovery of its association with vitamin C deficiency. We present the case of a 2-year-old boy, whose treatment for neuroblastoma was complicated by gastrointestinal disease, which necessitated enteral feeding. While still undergoing treatment, he started to complain about increasing pain in his lower limbs, which appeared to be markedly tender on palpation. Radiographic findings suggested a diagnosis of scurvy, which was subsequently confirmed on serum biochemistry. This was an unexpected finding, as the child had been receiving adequate vitamin C in his enteral feeds. However, his absorption had become severely impaired due to pseudomembranous gastritis and enteritis, leading to his deficient state. He significantly improved after intravenous ascorbic acid replacement and demonstrated a full recovery, both clinically and radiologically. This case highlights the importance of considering scurvy in the differential diagnosis for at-risk patients. Early recognition can facilitate the simple treatment of this potentially serious condition.

Some studies indicate that survival of AYAs with cancer may be inferior to that of younger children with similar cancers, possibly related (in part) to differences in access to centralised or standardised treatments. We sought to examine the comparative survival of paediatric & AYA patients in Ireland across a 20-year period.MethodsUsing the National Cancer Registry Ireland (NCRI) database, all patients diagnosed with a sarcoma age 0–24 between 1994–2014 were identified. Survival was based on matching of cases against national death certificate data complete up to 31 December 2014 & grouped in 2 diagnostic cohorts: 1994–2003 and 2004–2014 and examined according to the ICCC.Results577 patients less than 25 years were diagnosed with a sarcoma between 1994–2014; 321 under 15. Significantly poorer survival was noted for the AYA patients compared with paediatric patients for the following sarcoma groups and diagnosis periodsMalignant bone tumours, 1994–2013 (EHR 1.62, 1.05–2.48, P=0.026) and 1994–2003 (EHR 1.87, 1.05–3.33, P=0.032);Ewing & related tumours), 1994–2013 (EHR 2.04, 95% CI 1.11–3.72, P=0.021) and 1994–2003 (EHR 2.68, 95% CI 1.22–5.87, P=0.014);Soft tissue sarcomas), 1994–2013 (EHR 2.14, 1.29–3.53, P=0.03) and 2004–2013 (EHR 2.52, 1.20–5.25, P=0.014).ConclusionsThis study highlights the disparities that exist in outcomes for AYA patients with sarcomas treated in Ireland. The exact cause for this is unclear and is likely multifactorial, possibly owing to lack of standardised/centralised services. Future development on a national level is imperative.

Firefighters in Queensland are exposed to hot, humid weather conditions that contribute to the overall workload encountered during emergency operations. Responding to certain hazardous material incidents requires firefighters to wear fully encapsulated chemical protective suits for a maximum period of 20 minutes. The nature of these suits, combined with workload and environmental conditions, poses a potential heat stress problem for firefighters. This study evaluates the heat-induced physiological responses of firefighters while wearing fully encapsulated chemical protective suits in a senes of controlled thermal environments. Heart rate, body (aural) temperature, blood pressure, fluid loss, and a rating of perceived exertion were measured to evaluate the effect of increasing ambient air temperature during the performance of standard tasks. The results of the study indicated that the significant increase in heart rate, body temperature, and blood pressure was directly related to the increase in air temperature. The research indicates that the recommended suit wearing time of 20 minutes provided adequate physiological protection under the research conditions.

Abstract We present the case of a congenital localised sacrococcygeal primitive neuroectodermal tumor treated aggressively with surgical resection and modified age-appropriate adjuvant chemotherapy. The conventional combination chemotherapy of vincristine, adriamycin, cyclophosphamide, ifosfamide and etoposide was modified to a regimen including vincristine, adriamicin, cyclophosphamide and actinomycin in order to minimise the predicted toxicity in this age group. Adjuvant \"induction\" chemotherapy commenced at 4 weeks of age and consisted of four cycles of vincristine, adriamycin and cyclophosphamide at 50%, 75%, 75% and 100% of recommended doses (vincristine 0.05 mg/kg, adriamycin 0.83 mg/kg daily × 2, cyclophosphamide 40 mg/kg) at 3-weekly intervals. This was followed by four cycles of \"maintenance\" chemotherapy with vincristine (0.025 mg/kg), actinomycin (0.025 mg/kg) and cyclophosphamide (36 mg/kg) at full recommended doses. Cardioxane at a dose of 16.6 mg/kg was infused immediately prior to the adriamycin. Our patient is thriving at 19 months out from end of treatment.

IntroductionChildhood cancer is the second commonest cause of death in children in developed countries. Childhood cancer survival rates has improved over the last decade with the advancement of diagnostic procedures and continuous improvement of multimodal treatment strategies. According to the National Cancer Registry of Ireland, an average of 137 cancers were diagnosed per year in children under the age of 15 between 1994 and 2014. The 5-year overall survival rate for this entire cohort was 81%. It is well documented that survival rates in paediatric oncology vary depending on specific cancer diagnosis, age of the patient at diagnosis and disease stage.AimWe describe the incidence of cancer in very young children and the influence of age on outcome in children diagnosed with cancer in Ireland under the age of 1 between 2007–2017.MethodData were extracted from the database of the National Children’s Cancer Service (NCCS) based at Our Lady’s Children’s Hospital, Dublin. The data presented refer to the International Classification of Childhood Cancer (ICCC) version 3 with the inclusion of Langerhans Cell Histiocytosis (LCH).Result185 patients were diagnosed with paediatric cancer under the age of 1 at the time of their initial diagnosis. 159 (85.5%) patients were diagnosed with solid tumours or LCH. 86 (46.5%) were male. The average age at diagnosis was 5.24 (range 0–12) months. 19 (10.3%) patients were diagnosed following an abnormal antenatal scan. The most common cancers diagnosed were neuroblastoma (22.7%), CNS tumours (19.5%) and leukaemia (13.5%).158 (85.5%) patients received treatment. 124 (78.4%) patients received chemotherapy as part of their treatment. 20 (12.7%) patients received radiotherapy. The mean age for radiotherapy was 1.35 years (range 0.17–4). 18 (9.7%) patients received stem cell transplant/rescue. The cumulative overall survival rate at 5 years is 80%. CNS tumours have the worst prognosis followed by leukaemias. 35 (18.9%) patients have relapsed during follow up, and 20 are alive in follow-up.ConclusionIncidence rates of specific paediatric cancer types vary according to the age at diagnosis. There is no difference in survival rates between children diagnosed with cancer under 1 year of age and older children. Outcomes at the NCCS compare favourably with international standards.

Non-Hodgkin's lymphoma and Hodgkin's lymphoma constitute 60% and 40% respectively of the pediatric lymphomas, which are the third most common type of malignant disease in North American children.2 [Burkitt]'s lymphoma is the most common subtype of non-Hodgkin's lymphoma, with an incidence of 2 cases per million children in North America (sporadic variety) and up to 100 cases per million children in equatorial Africa (endemic variety).3 It is believed that the Epstein-Barr virus plays a causal role, particularly in Africa. Burkitt's lymphoma is characterized by a clonal proliferation of relatively mature B cells, and the majority of cases contain a chromosomal translocation - t(8;14) - that leads to uncontrolled expression of a proto-oncogene. Endemic Burkitt's lymphoma has a peak incidence among children 11 years old, usually presenting with the classic jaw tumour and occasionally involving the gastrointestinal tract and kidneys. This is in contrast to the sporadic type, whose peak incidence is among children 7 years old and whose presentation largely involves the gastrointestinal tract. This results from direct involvement of Peyer's patches, and affected children commonly present with an abdominal mass or pain, distendon, nausea and vomiting. Intussusception, obstruction or perforation may occur.4 However, presentation with bleeding in the upper gastrointestinal tract, as in the case we have described, has not been previously reported to our knowledge. Other common potential sites affected by the sporadic form of Burkitt's lymphoma include tonsils or adenoids, bone marrow, bone, kidneys, testes, the central nervous system and salivary glands. Both forms of Burkitt's lymphoma occur more often in boys than in girls, at a ratio of 2-3:1.

Near Field Communication Technology has become one of the most talked about technologies in recent years due to its emerging developments, providing close range communication between mobile phones and other NFC enabled devices. Because near field communication has become increasingly relevant within society, a basic understanding of the technology along with its uses is necessary, in order to maintain growth and innovation. In addition to examining the uses of near field communication this paper also turns to relevance when dealing with the different industries the technology has been implemented in. With the integration of any new technology there are always unknown factors that may be present, this paper aims to quell some of those concerns by addressing some of the most relevant questions about the technology. The purpose of this research was to evaluate how the integration of near field communication affects user security in bill pay? How the integration of near field communication technology in automobiles affect or change driver safety? How the integration of near field communication technology in the health care field affects or changes the patient’s ability to monitor their health? The evolution of near field communication has proposed many new short range wireless technologies in recent years. Constantly looking for new and innovative ways to improve upon the current technology, making each iteration faster, simpler, and safer to use from a consumer standpoint. Emerging from a combination of technologies near field communication now encompasses an enormous array of devices that look to play an increasingly important role in electronic commerce and other short ranged wireless technologies now and well into the future. Keywords: Professor Riddell, Bill Pay, Cyber Security Intelligence, Integration, Near Field Communication, Technology, (NFC) Enabled Devices, Mobile Payments.

Nat. Genet. 47, 1471–1474 (2015); published online 9 November 2015; corrected after print 8 February 2016 In the version of this article initially published, the authors failed to acknowledge funding from the NIHR Biomedical Research Centre at Great Ormond Street Hospital for Children NHS FoundationTrust and University College London to Neil Sebire.