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BACKGROUND: Schools with formal sun safety polices generally show better sun safety practices than schools without. OBJECTIVES: To understand the extent to which Welsh primary schools have sun safety policies; to identify the key characteristics of policies; to assess whether policy adoption varies by school characteristics; and to consider what support schools need to develop sun safety policies. METHODS: An online multiple-choice survey on sun safety was distributed to all 1241 primary schools in Wales. RESULTS: In total, 471 (38.0%) schools responded. Of these, 183 (39.0%) reported having a formal sun safety policy. Welsh medium schools (P = 0.036) and schools in North Wales (P = 0.008) were more likely to report having a policy. Schools with a higher percentage of pupils receiving free school meals (P = 0.046) and with lower attendance rates (P = 0.008) were less likely to report having a sun safety policy. The primary reasons for schools not having a policy included being 'not aware of the need' (34.6%); 'need assistance with policy or procedure development' (30.3%); and 'not got around to it just yet' (26.8%). CONCLUSIONS: With less than half of schools reporting a sun safety policy and variation in the presence/absence of a policy by school characteristics, our survey revealed inconsistency in formal sun safety provision in Welsh schools. The findings also suggest that schools are unaware of the importance of sun safety and need support to develop and implement policies. This snapshot of the current situation in primary schools in Wales provides a basis upon which the comprehensiveness, effectiveness and implementation of sun safety policies can be further evaluated.
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Instituciones Académicas , Gales , Humanos , Instituciones Académicas/estadística & datos numéricos , Niño , Quemadura Solar/prevención & control , Política de Salud , Encuestas y Cuestionarios , Protectores Solares/uso terapéutico , Ropa de Protección/estadística & datos numéricos , Luz Solar/efectos adversos , Masculino , Femenino , Servicios de Salud Escolar/normasRESUMEN
BACKGROUND: Skin cancer rates are on the rise globally. School sun safety programmes are recommended by the World Health Organisation to reduce the risk of future skin cancer at population level; however, these are encouraged but not mandated in Wales. OBJECTIVES: To explore current sun protection practices and sun safety education in primary schools in Wales and whether these are linked to the existence of a formal sun safety policy. METHODS: An online survey to all 1241 Welsh primary schools asking about sun safety practices, education and formal policies. RESULTS: 471 (38.0%) schools responded with the profile of responding schools generally matching the profile of schools in Wales. A minority (22,4.7%) of responding schools reported they had sufficient shade for most activities. In the spring and summer terms almost two thirds of schools encourage hat wearing (304, 64.8%) and sunscreen (296, 63.2%). While nearly all schools reported that parents were encouraged to apply sunscreen to students before school (449, 95.7%), there was wide variation in other sunscreen application practices. Less than one third of schools (129, 29.0%) reported that they include sun protection education in the curriculum in every year group, with 11.7% (52) including this in certain years only.Schools with a formal policy were more likely to report more comprehensive sun protection practices including having sufficient shade [OR 1.51, 95% CI 1.04-2.19; p = 0.032], having spare hats for pupils to wear [OR 1.59, 95% CI 1.07-2.37; p = 0.023], providing guidance for staff [OR 5.87, 95% CI 3.05-11.28; p < 0.001], encouraging them to model sun safe behaviours [OR 1.82, 95% CI 1.18-2.80; p = 0.007] and teaching sun protection education as part of the curriculum in every year group [OR 2.56, 95% CI 1.76-3.71; p < 0.001]. With respect to sunscreen, the existence of a formal policy did not seem to affect a school's practice. CONCLUSIONS: While in most cases, the existence of a formal policy suggests more comprehensive sun protection practices and education in schools, sun protection measures and education need improvement across the primary school sector in Wales to reverse rising skin cancer rates.
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Chronic graft-versus-host disease (cGVHD) of the skin is a serious cause of long-term morbidity and mortality among patients who receive hematopoietic stem cell transplants. Systemic corticosteroids remain first-line treatment for cutaneous cGVHD; however, there is currently no consensus on second-line therapy for steroid-refractory disease. We herein present a case of a pediatric patient with severe cGVHD of the skin, nonresponsive to corticosteroids, who was successfully treated with a prolonged course of ruxolitinib with minimal side effects.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Corticoesteroides/uso terapéutico , Niño , Enfermedad Crónica , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Nitrilos , Pirazoles , Pirimidinas , Estudios Retrospectivos , Esteroides/uso terapéuticoRESUMEN
BACKGROUND: Fleas (Insecta: Siphonaptera) are small flightless parasites of birds and mammals; their blood-feeding can transmit many serious pathogens (i.e., the etiological agents of bubonic plague, endemic and murine typhus). The lack of flea genome assemblies has hindered research, especially comparisons to other disease vectors. Accordingly, we sequenced the genome of the cat flea, Ctenocephalides felis, an insect with substantial human health and veterinary importance across the globe. RESULTS: By combining Illumina and PacBio sequencing of DNA derived from multiple inbred female fleas with Hi-C scaffolding techniques, we generated a chromosome-level genome assembly for C. felis. Unexpectedly, our assembly revealed extensive gene duplication across the entire genome, exemplified by ~ 38% of protein-coding genes with two or more copies and over 4000 tRNA genes. A broad range of genome size determinations (433-551 Mb) for individual fleas sampled across different populations supports the widespread presence of fluctuating copy number variation (CNV) in C. felis. Similarly, broad genome sizes were also calculated for individuals of Xenopsylla cheopis (Oriental rat flea), indicating that this remarkable "genome-in-flux" phenomenon could be a siphonapteran-wide trait. Finally, from the C. felis sequence reads, we also generated closed genomes for two novel strains of Wolbachia, one parasitic and one symbiotic, found to co-infect individual fleas. CONCLUSION: Rampant CNV in C. felis has dire implications for gene-targeting pest control measures and stands to complicate standard normalization procedures utilized in comparative transcriptomics analysis. Coupled with co-infection by novel Wolbachia endosymbionts-potential tools for blocking pathogen transmission-these oddities highlight a unique and underappreciated disease vector.
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Ctenocephalides/genética , Variaciones en el Número de Copia de ADN , Duplicación de Gen , Tamaño del Genoma , Animales , Cromosomas , Femenino , MasculinoRESUMEN
BACKGROUND: Unrecognised and untreated parental mental illness is a major adverse childhood experience with potentially life-long consequences for health and wellbeing. In the United Kingdom (UK) health visitors provide a universal health promotion service to children aged 0-5 years, which includes safeguarding. This preventive work is highly relevant to policy aims of improving outcomes for children living with adverse childhood experiences, but is currently under researched. The aim of this study was to explore how health visitors promote young children's wellbeing when a parent has a mental health problem, and to co-produce strategies to improve child health outcomes. METHODS: A mixed methods study was conducted, consisting of a cross-sectional survey and consensus workshops in Wales, UK. In phase 1 health visitors (n = 174) responded to an online questionnaire designed to explore the nature and scope of their preventive work with families experiencing mental ill health. For phase 2 providers of health and other support services (n = 38) took part in Nominal Group Technique workshops to co-produce strategies for better joint working to protect the wellbeing of children living with parental ill health. RESULTS: We identified that health visitors routinely provide support to families where parents have a range of mental health problems, including severe mental illness. Most practice is focused on mothers with depression, and fewer respondents were confident about working with fathers. Unmet training needs were identified in relation to adult mental illness, particularly the impact upon children. Solutions to working more effectively with professional and voluntary agencies included raising awareness of professional roles and responsibilities, timely two-way communication, taking a strengths-based approach and maintaining a focus on the child. CONCLUSIONS: This study provided evidence on the range of parental mental ill health encountered by health visitors and the strategies they use to protect children's wellbeing. Increasing the effectiveness of joint working is key to improving outcomes for babies and young children, including greater use of voluntary sector services. This study has implications for those who commission and provide health and welfare services for children, and adult mental health services.
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Salud Infantil , Hijo de Padres Discapacitados , Promoción de la Salud , Trastornos Mentales , Enfermeros de Salud Comunitaria/psicología , Preescolar , Estudios Transversales , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Encuestas y Cuestionarios , GalesRESUMEN
BACKGROUND: The ELIANA trial showed that 61 (81%) of 75 paediatric and young adult patients with relapsed or refractory B-cell acute lymphoblastic leukaemia achieved overall remission after treatment with tisagenlecleucel, a chimeric antigen receptor targeted against the CD19 antigen. We aimed to evaluate patient-reported quality of life in these patients before and after tisagenlecleucel infusion. METHODS: ELIANA, a global, single-arm, open-label, phase 2 trial, was done in 25 hospitals across Australia, Austria, Belgium, Canada, France, Germany, Italy, Japan, Norway, Spain, and the USA. Patients with B-cell acute lymphoblastic leukaemia aged at least 3 years at the time of screening and 21 years or younger at the time of initial diagnosis who were in second or greater bone marrow relapse, chemorefractory, relapsed after allogeneic stem-cell transplantation, or were otherwise ineligible for allogeneic stem-cell transplantation were enrolled. Patients received a single intravenous administration of a target dose of 0·2-5â×â106 transduced viable T cells per kg for patients weighing 50 kg or less or 0·1-2·5â×â108 transduced viable T cells for patients weighing more than 50 kg. The primary outcome, reported previously, was the proportion of patients who achieved remission. A prespecified secondary endpoint, reported here, was patient-reported quality of life measured with the Pediatric Quality of Life Inventory (PedsQL) and European Quality of Life-5 Dimensions questionnaire (EQ-5D). Patients completed the questionnaires at baseline, day 28, and months 3, 6, 9, and 12 after treatment. The data collected were summarised using descriptive statistics and post-hoc mixed models for repeated measures. Change from baseline response profiles were illustrated with cumulative distribution function plots. The proportion of patients achieving the minimal clinically important difference and normative mean value were reported. Analysis was per protocol. This study is registered with ClinicalTrials.gov, NCT02435849. FINDINGS: Between April 8, 2015, and April 25, 2017, 107 patients were screened, 92 were enrolled, and 75 received tisagenlecleucel. 58 patients aged 8-23 years were included in the analysis of quality of life. At baseline, 50 (86%) patients had completed the PedsQL questionnaire and 48 (83%) had completed the EQ-5D VAS. Improvements in patient-reported quality-of-life scores were observed for all measures at month 3 after tisagenlecleucel infusion (mean change from baseline to month 3 was 13·3 [95% CI 8·9-17·6] for the PedsQL total score and 16·8 [9·4-24·3] for the EQ-5D visual analogue scale). 30 (81%) of 37 patients achieved the minimal clinically important difference at month 3 for the PedsQL total score and 24 (67%) of 36 patients achieved this for the EQ-5D visual analogue scale. INTERPRETATION: These findings, along with the activity and safety results of ELIANA, suggest a favourable benefit-risk profile of tisagenlecleucel in the treatment of paediatric and young adult patients with relapsed or refractory B-cell acute lymphoblastic leukaemia. FUNDING: Novartis.
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Resistencia a Antineoplásicos , Recurrencia Local de Neoplasia/terapia , Medición de Resultados Informados por el Paciente , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Calidad de Vida , Receptores de Antígenos de Linfocitos T/administración & dosificación , Terapia Recuperativa , Adolescente , Adulto , Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Niño , Femenino , Estudios de Seguimiento , Humanos , Inmunoterapia/métodos , Infusiones Intravenosas , Masculino , Recurrencia Local de Neoplasia/patología , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patología , Pronóstico , Tasa de Supervivencia , Adulto JovenRESUMEN
Infections and graft-versus-host disease (GVHD) have historically resulted in high mortality among children undergoing umbilical cord blood transplantation (UCBT). However, recent advances in clinical practice have likely improved outcomes of these patients. We conducted a retrospective cohort study of children (<18years of age) undergoing UCBT at Duke University between January 1, 1995 and December 31, 2014. We compared 2-year all-cause and cause-specific mortality during 3 time periods based on year of transplantation (1995 to 2001, 2002 to 2007, and 2008 to 2014). We used multivariable Cox regression to identify demographic and UCBT characteristics that were associated with all-cause mortality, transplantation-related mortality, and death from invasive aspergillosis after adjustment for time period. During the 20-year study period 824 children underwent UCBT. Two-year all-cause mortality declined from 48% in 1995 to 2001 to 30% in 2008 to 2014 (Pâ¯=â¯.0002). White race and nonmalignant UCBT indications were associated with lower mortality. Black children tended to have a higher risk of death for which GVHD (18% versus 11%; Pâ¯=â¯.06) or graft failure (9% versus 3%; Pâ¯=â¯.01) were contributory than white children. Comparing 2008 to 2014 with 1995 to 2001, more than half (59%) of the reduced mortality was attributable to a reduction in infectious mortality, with 45% specifically related to reduced mortality from invasive aspergillosis. Antifungal prophylaxis with voriconazole was associated with lower mortality from invasive aspergillosis than low-dose amphotericin B lipid complex (hazard ratio, .09; 95% confidence interval, .01 to .76). With the decline in mortality from invasive aspergillosis, adenovirus and cytomegalovirus have become the most frequentinfectious causes of death in children after UCBT. Advances in clinical practice over the past 20years improved survival of children after UCBT. Reduced mortality from infections, particularly invasive aspergillosis, accounted for the largest improvement in survival and was associated with use of voriconazole for antifungal prophylaxis.
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Trasplante de Células Madre de Sangre del Cordón Umbilical/mortalidad , Estudios de Cohortes , Femenino , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Masculino , Estudios Retrospectivos , Tasa de Supervivencia , Factores de TiempoRESUMEN
Allogeneic hematopoietic stem cell transplantation is curative for primary immunodeficiencies. Bone marrow from an unaffected human leukocyte antigen (HLA)-identical sibling donor is the ideal graft source. For minor donors, meaningful consent or assent may not be feasible, and permission from parents or legal guardians is considered acceptable. Adverse events, albeit extremely small, can be associated with bone marrow harvest in pediatric donors. Donor safety concerns potentially increase with multiple bone marrow harvests. Very little is known about multiple bone marrow harvests from pediatric donors. We describe the ethical considerations and clinical decision-making in an unusual clinical situation where three patients with the same primary immunodeficiency were HLA identical to one another and their younger sibling, who underwent bone marrow harvests three times between 1.3 and 4 years of age, resulting in successful transplantation for all three patients. We hope that this experience will provide guidance to providers and families in a similar situation.
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Discusiones Bioéticas , Trasplante de Médula Ósea/ética , Trasplante de Células Madre Hematopoyéticas/etnología , Síndromes de Inmunodeficiencia/terapia , Hermanos , Donantes de Tejidos , Preescolar , Femenino , Humanos , Lactante , MasculinoRESUMEN
Rickettsia species are obligate intracellular bacteria with both conserved and lineage-specific strategies for invading and surviving within eukaryotic cells. One variable component of Rickettsia biology involves arthropod vectors: for instance, typhus group rickettsiae are principally vectored by insects (i.e., lice and fleas), whereas spotted fever group rickettsiae are exclusively vectored by ticks. For flea-borne Rickettsia typhi, the etiological agent of murine typhus, research on vertebrate host biology is facilitated using cell lines and animal models. However, due to the lack of any stable flea cell line or a published flea genome sequence, little is known regarding R. typhi biology in flea vectors that, importantly, do not suffer lethality due to R. typhi infection. To address if fleas combat rickettsial infection, we characterized the cat flea (Ctenocephalides felis) innate immune response to R. typhi Initially, we determined that R. typhi infects Drosophila cells and increases antimicrobial peptide (AMP) gene expression, indicating immune pathway activation. While bioinformatics analysis of the C. felis transcriptome identified homologs to all of the Drosophila immune deficiency (IMD) and Toll pathway components, an AMP gene expression profile in Drosophila cells indicated IMD pathway activation upon rickettsial infection. Accordingly, we assessed R. typhi-mediated flea IMD pathway activation in vivo using small interfering RNA (siRNA)-mediated knockdown. Knockdown of Relish and Imd increased R. typhi infection levels, implicating the IMD pathway as a critical regulator of R. typhi burden in C. felis These data suggest that targeting the IMD pathway could minimize the spread of R. typhi, and potentially other human pathogens, vectored by fleas.
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Ctenocephalides/inmunología , Infestaciones por Pulgas/inmunología , Infecciones por Rickettsia/inmunología , Rickettsia typhi/inmunología , Transducción de Señal/inmunología , Siphonaptera/inmunología , Adenosina Monofosfato/metabolismo , Animales , Gatos , Línea Celular , Chlorocebus aethiops , Ctenocephalides/microbiología , Drosophila/microbiología , Infestaciones por Pulgas/microbiología , Expresión Génica/inmunología , Inmunidad Innata/inmunología , Insectos Vectores/inmunología , Insectos Vectores/microbiología , Siphonaptera/microbiología , Tifus Endémico Transmitido por Pulgas/inmunología , Tifus Endémico Transmitido por Pulgas/microbiología , Células VeroRESUMEN
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder of immune dysregulation characterized by fever, hepatosplenomegaly, cytopenias, central nervous system disease, increased inflammatory markers, and hemophagocytosis. Currently, allogeneic hematopoietic stem cell transplantation is the only curative approach for patients with HLH, with reported survival ranging from 50% to 70% with myeloablative conditioning (MAC) regimens. However, donor availability and transplantation-related mortality associated with conventional MAC are major barriers to success. Unrelated umbilical cord blood transplantation (UCBT) provides a readily available alternative donor source for patients lacking matched related donors. Accordingly, we report the results of UCBT in 14 children treated between 1998 and 2016. All children received standard HLH chemotherapy before UCBT. The median age at diagnosis was 2.7 months (range, .8 to 10.4) and at transplantation was 7.5 months (range, 3.8 to 17). Ten patients received MAC with busulfan/cyclophosphamide/etoposide /antithymocyte globulin (ATG) (n = 5), busulfan/cyclophosphamide /ATG (n = 4), or busulfan /melphalan/ATG (n = 1). Four patients received reduced-toxicity conditioning (RTC) with alemtuzumab/fludarabine/melphalan/hydroxyurea ± thiotepa. Cord blood units were mismatched at either 1 (n = 9) or 2 (n = 5) loci and delivered a median total nucleated cell dose of 11.9 × 107/kg (range, 4.6 to 27.9) and CD34+ dose of 3.1 × 105/kg (range, 1.1 to 6.8). The cumulative incidence of neutrophil engraftment by day 42 was 78.6% (95% confidence interval [CI], 42.9% to 93.4%) with a median of 19 days (range, 13 to 27), and that for platelet (50,000) engraftment by day 100 was 64.3% (95% CI, 28.2% to 85.7%) with a median of 51 days (range, 31 to 94). Six patients developed either grade II (n = 5) or grade IV (n = 1) acute graft-versus-host disease (GVHD); no extensive chronic GVHD was seen. Ten patients (71.4%) are alive and well at a median of 11.2 years after transplantation (range, .85 to 18.25), 9 of whom maintain sustained full donor chimerism after a single UCBT, whereas 1 patient with autologous recovery after first UCBT with RTC has achieved full donor chimerism after a second UCBT with MAC. This series demonstrates that, in combination with standard HLH therapy, UCBT after MAC or RTC conditioning can provide long-term survival with durable complete donor chimerism comparable to that of conventional donors. UCBT should be considered for patients with HLH lacking a fully matched related or unrelated adult donor.
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Quimerismo , Trasplante de Células Madre de Sangre del Cordón Umbilical/métodos , Linfohistiocitosis Hemofagocítica/terapia , Adolescente , Niño , Preescolar , Trasplante de Células Madre de Sangre del Cordón Umbilical/efectos adversos , Trasplante de Células Madre de Sangre del Cordón Umbilical/mortalidad , Trasplante de Células Madre de Sangre del Cordón Umbilical/normas , Supervivencia sin Enfermedad , Sangre Fetal/citología , Supervivencia de Injerto , Enfermedad Injerto contra Huésped , Humanos , Lactante , Linfohistiocitosis Hemofagocítica/complicaciones , Linfohistiocitosis Hemofagocítica/mortalidad , Acondicionamiento Pretrasplante/métodosRESUMEN
PURPOSE: At our institution, a high proportion of children with onychocryptosis (ingrown toenail) requiring surgical intervention were noted to have a history of hematopoietic stem cell transplantation (HSCT). We analyzed the characteristics of patients who underwent surgical intervention for onychocryptosis and examined our institutional HSCT database to determine if an association exists between onychocryptosis and HSCT. MATERIALS AND METHODS: Surgical cases for onychocryptosis performed from 2000 to 2012 were identified. Nine demographic, clinical, and perioperative variables for both patients with and without prior HSCT were assessed. In a separate analysis, the institutional HSCT database was then queried to identify the prevalence and clinical characteristics associated with onychocryptosis after HSCT. RESULTS: We identified 17 children who had undergone surgical management of onychocryptosis, of which 8 (47.1%) had previous HSCT. Children who had undergone HSCT had an aggressive form of onychocryptosis with 50.0% having bilateral great toe and nail edge involvement and 37.5% having a recurrence. In HSCT cohort analysis of 1069 children, 91 (8.5%) had onychocryptosis. Male sex, non-black race, acute graft versus host disease, and increasing age at transplantation were independently associated with onychocryptosis. CONCLUSIONS: HSCT is strongly associated with onychocryptosis requiring surgical intervention. Children with a history of HSCT may also have more aggressive toenail disease, with higher rates of surgical intervention, bilateral ingrown toenails, recurrence, and need for return to the operating room. Clinicians should perform careful screening and early treatment in these patients.
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Trasplante de Células Madre Hematopoyéticas/efectos adversos , Uñas Encarnadas/cirugía , Adolescente , Factores de Edad , Niño , Femenino , Enfermedad Injerto contra Huésped , Humanos , Masculino , Grupos Raciales , Factores de Riesgo , Factores SexualesRESUMEN
INTRODUCTION: The aims of this study were to produce a population-based estimate of the prevalence of work-related exposure to formaldehyde, to identify the main circumstances of exposure and to describe the use of workplace control measures designed to decrease those exposures. METHODS: The analysis used data from the Australian Workplace Exposures Study, a nationwide telephone survey, which investigated the current prevalence and exposure circumstances of work-related exposure to 38 known or suspected carcinogens, including formaldehyde, among Australian workers aged 18-65 years. Using the web-based tool OccIDEAS, semi-quantitative information was collected about exposures in the current job held by the respondent. Questions were addressed primarily at tasks undertaken rather than about self-reported exposures. RESULTS: Of the 4993 included respondents, 124 (2.5%) were identified as probably being exposed to formaldehyde in the course of their work [extrapolated to 2.6% of the Australian working population-265 000 (95% confidence interval 221 000-316 000) workers]. Most (87.1%) were male. About half worked in technical and trades occupations. In terms of industry, about half worked in the construction industry. The main circumstances of exposure were working with particle board or plywood typically through carpentry work, building maintenance, or sanding prior to painting; with the more common of other exposures circumstances being firefighters involved in fighting fires, fire overhaul, and clean-up or back-burning; and health workers using formaldehyde when sterilizing equipment or in a pathology laboratory setting. The use of control measures was inconsistent. CONCLUSION: Workers are exposed to formaldehyde in many different occupational circumstances. Information on the exposure circumstances can be used to support decisions on appropriate priorities for intervention and control of occupational exposure to formaldehyde, and estimates of burden of cancer arising from occupational exposure to formaldehyde.
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Formaldehído/análisis , Exposición Profesional/análisis , Adulto , Contaminantes Ocupacionales del Aire/análisis , Australia/epidemiología , Carcinógenos/análisis , Femenino , Formaldehído/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Profesionales/inducido químicamente , Enfermedades Profesionales/epidemiología , Exposición Profesional/efectos adversos , Exposición Profesional/prevención & control , Ocupaciones/estadística & datos numéricos , Prevalencia , Encuestas y Cuestionarios , Adulto JovenRESUMEN
INTRODUCTION: The aims of this study were to produce a population-based estimate of the prevalence of work-related exposure to lead and its compounds, to identify the main circumstances of exposures, and to collect information on the use of workplace control measures designed to decrease those exposures. METHODS: Data came from the Australian Workplace Exposures Study, a nationwide telephone survey which investigated the current prevalence and circumstances of work-related exposure to 38 known or suspected carcinogens, including lead, among Australian workers aged 18-65 years. Using the web-based tool, OccIDEAS, semi-quantitative information was collected about exposures in the current job held by the respondent. Questions were addressed primarily at tasks undertaken rather than about self-reported exposures. RESULTS: A total of 307 (6.1%) of the 4993 included respondents were identified as probably being exposed to lead in the course of their work. Of these, almost all (96%) were male; about half worked in trades and technician-related occupations, and about half worked in the construction industry. The main tasks associated with probable exposures were, in decreasing order: soldering; sanding and burning off paint while painting old houses, ships, or bridges; plumbing work; cleaning up or sifting through the remains of a fire; radiator-repair work; machining metals or alloys containing lead; mining; welding leaded steel; and working at or using indoor firing ranges. Where information on control measures was available, inconsistent use was reported. Applied to the Australian working population, approximately 6.3% [95% confidence interval (CI) = 5.6-7.0] of all workers (i.e. 631000, 95% CI 566000-704000 workers) were estimated to have probable occupational exposure to lead. CONCLUSIONS: Lead remains an important exposure in many different occupational circumstances in Australia and probably other developed countries. This information can be used to support decisions on priorities for intervention and control of occupational exposure to lead and estimates of burden of cancer arising from occupational exposure to lead.
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Plomo/análisis , Exposición Profesional/análisis , Lugar de Trabajo , Adolescente , Adulto , Anciano , Australia/epidemiología , Carcinógenos/análisis , Estudios Transversales , Femenino , Humanos , Plomo/efectos adversos , Masculino , Persona de Mediana Edad , Enfermedades Profesionales/inducido químicamente , Enfermedades Profesionales/epidemiología , Exposición Profesional/efectos adversos , Exposición Profesional/prevención & control , Ocupaciones/estadística & datos numéricos , Prevalencia , Factores de Riesgo , Encuestas y Cuestionarios , Adulto JovenRESUMEN
INTRODUCTION: The aims of this study were to produce a population-based estimate of the prevalence of work-related exposure to polycyclic aromatic hydrocarbons (PAHs), to identify the main circumstances of exposure and to describe the use of workplace control measures designed to decrease those exposures. METHODS: The analysis used data from the Australian Workplace Exposures Study, a nationwide telephone survey which investigated the current prevalence and exposure circumstances of work-related exposure to 38 known or suspected carcinogens, including PAHs, among Australian workers aged 18-65 years. Using the web-based tool OccIDEAS, semi-quantitative information was collected about exposures in the current job held by the respondent. Questions were addressed primarily at tasks undertaken rather than about self-reported exposures. RESULTS: Of the 4,993 included respondents, 297 (5.9%) were identified as probably being exposed to PAHs in their current job [extrapolated to 6.7% of the Australian working population-677 000 (95% confidence interval 605 000-757 000) workers]. Most (81%) were male; about one-third were farmers and about one-quarter worked in technical and trades occupations. In the agriculture industry about half the workers were probably exposed to PAHs. The main exposure circumstances were exposure to smoke through burning, fighting fires or through maintaining mowers or other equipment; cleaning up ash after a fire; health workers exposed to diathermy smoke; cooking; and welding surfaces with a coating. Where information on control measures was available, their use was inconsistent. CONCLUSION: Workers are exposed to PAHs in many different occupational circumstances. Information on the exposure circumstances can be used to support decisions on appropriate priorities for intervention and control of occupational exposure to PAHs, and estimates of burden of cancer arising from occupational exposure to PAHs.
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Exposición Profesional/análisis , Hidrocarburos Policíclicos Aromáticos/análisis , Adolescente , Adulto , Anciano , Australia/epidemiología , Carcinógenos , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Profesionales/inducido químicamente , Enfermedades Profesionales/epidemiología , Exposición Profesional/efectos adversos , Exposición Profesional/prevención & control , Ocupaciones/estadística & datos numéricos , Hidrocarburos Policíclicos Aromáticos/efectos adversos , Prevalencia , Adulto JovenRESUMEN
BACKGROUND: Respirable crystalline silica (RCS) is a biologically active dust that can accumulate in the lung and induce silicosis and lung cancer. Despite occupational exposure being the predominant source, no study has described current occupational RCS exposure on a national scale in Australia. The aim of this study is to estimate the characteristics of those exposed and the circumstances of RCS exposure in Australian workplaces. METHODS: A cross-sectional survey of the Australian working population (18-65 years old) was conducted. Information about the respondents' current job and their demographic characteristics was collected in a telephone interview. Occupational exposure to RCS was determined based on preprogrammed decision rules regarding potential levels of exposure associated with self-reported tasks. RESULTS: Overall, 6.4% of respondents were deemed exposed to RCS at work in 2012 (3.3% were exposed at a high level). The exposure varied with sex, state of residence, and socioeconomic status. Miners and construction workers were most likely to be highly exposed to RCS when performing tasks with concrete or cement or working near crushers that create RCS-containing dusts. When extrapolated to the entire Australian working population, 6.6% of Australian workers were exposed to RCS and 3.7% were highly exposed when carrying out tasks at work. CONCLUSION: This is the first study investigating occupational RCS exposure in an entire national working population. The information about occupational tasks that lead to high level RCS exposure provided by this study will inform the direction of occupational interventions and policies.
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Contaminantes Ocupacionales del Aire/análisis , Exposición por Inhalación/análisis , Exposición Profesional/análisis , Ocupaciones/estadística & datos numéricos , Dióxido de Silicio/análisis , Australia , Industria de la Construcción , Estudios Transversales , Polvo , Femenino , Humanos , Masculino , Minería , Prevalencia , Lugar de TrabajoRESUMEN
The Pathosystems Resource Integration Center (PATRIC) is the all-bacterial Bioinformatics Resource Center (BRC) (http://www.patricbrc.org). A joint effort by two of the original National Institute of Allergy and Infectious Diseases-funded BRCs, PATRIC provides researchers with an online resource that stores and integrates a variety of data types [e.g. genomics, transcriptomics, protein-protein interactions (PPIs), three-dimensional protein structures and sequence typing data] and associated metadata. Datatypes are summarized for individual genomes and across taxonomic levels. All genomes in PATRIC, currently more than 10,000, are consistently annotated using RAST, the Rapid Annotations using Subsystems Technology. Summaries of different data types are also provided for individual genes, where comparisons of different annotations are available, and also include available transcriptomic data. PATRIC provides a variety of ways for researchers to find data of interest and a private workspace where they can store both genomic and gene associations, and their own private data. Both private and public data can be analyzed together using a suite of tools to perform comparative genomic or transcriptomic analysis. PATRIC also includes integrated information related to disease and PPIs. All the data and integrated analysis and visualization tools are freely available. This manuscript describes updates to the PATRIC since its initial report in the 2007 NAR Database Issue.
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Bases de Datos Genéticas , Genoma Bacteriano , Bacterias/clasificación , Bacterias/genética , Infecciones Bacterianas/microbiología , Proteínas Bacterianas/química , Proteínas Bacterianas/metabolismo , Técnicas de Tipificación Bacteriana , Perfilación de la Expresión Génica , Genómica , Humanos , Internet , Conformación Proteica , Mapeo de Interacción de ProteínasRESUMEN
BACKGROUND: Road transport workers (RTWs) are at high risk of exposure to several occupational carcinogens. However, there are gaps in knowledge regarding the extent and the circumstances of exposure. As a sub-study of the Australian Work Exposures Study, this study investigated the prevalence of occupational exposure in Australian RTWs. METHODS: A random sample of Australian working population was invited to a telephone interview regarding their current jobs. An automated expert-assessment procedure was applied to self-reported job-related tasks using a web-based application. 162 RTWs were included in this study. RESULTS: RTWs were exposed to diesel exhaust (97%), solar ultraviolet radiation (78%), environmental tobacco smoke (55%), benzene (29%), silica (15%), and asbestos (10%) at work. Besides driving on roads, vehicle maintenance-related tasks were the major source of carcinogen exposures among RTWs. DISCUSSION: Most RTWs are exposed to at least one carcinogen at work. We have identified tasks where the use of control measures could potentially reduce exposures.
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Conducción de Automóvil , Carcinógenos Ambientales/análisis , Vehículos a Motor , Exposición Profesional/análisis , Ocupaciones , Adolescente , Adulto , Amianto/análisis , Australia/epidemiología , Benceno/análisis , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dióxido de Silicio/análisis , Contaminación por Humo de Tabaco/análisis , Rayos Ultravioleta , Emisiones de Vehículos/análisis , Adulto JovenRESUMEN
Generation of patient-derived, autologous dendritic cells (DCs) is a critical component of cancer immunotherapy with ex vivo-generated, tumor antigen-loaded DCs. An important factor in the ability to generate DCs is the potential impact of prior therapies on DC phenotype and function. We investigated the ability to generate DCs using cells harvested from pediatric patients with medulloblastoma for potential evaluation of DC-RNA based vaccination approach in this patient population. Cells harvested from medulloblastoma patient leukapheresis following induction chemotherapy and granulocyte colony stimulating factor mobilization were cryopreserved prior to use in DC generation. DCs were generated from the adherent CD14+ monocytes using standard procedures and analyzed for cell recovery, phenotype and function. To summarize, 4 out of 5 patients (80%) had sufficient monocyte recovery to permit DC generation, and we were able to generate DCs from 3 out of these 4 patient samples (75%). Overall, we successfully generated DCs that met phenotypic requisites for DC-based cancer therapy from 3 out of 5 (60%) patient samples and met both phenotypic and functional requisites from 2 out of 5 (40%) patient samples. This study highlights the potential to generate functional DCs for further clinical treatments from refractory patients that have been heavily pretreated with myelosuppressive chemotherapy. Here we demonstrate the utility of evaluating the effect of the currently employed standard-of-care therapies on the ex vivo generation of DCs for DC-based clinical studies in cancer patients.
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Neoplasias Encefálicas/patología , Células Dendríticas/fisiología , Quimioterapia de Inducción , Leucaféresis , Meduloblastoma/patología , Antígenos CD/metabolismo , Neoplasias Encefálicas/tratamiento farmacológico , Separación Celular , Niño , Técnicas de Cocultivo , Pruebas Inmunológicas de Citotoxicidad , Células Dendríticas/efectos de los fármacos , Células Dendríticas/patología , Citometría de Flujo , Factor Estimulante de Colonias de Granulocitos/farmacología , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Humanos , Proteínas Inhibidoras de la Apoptosis/genética , Proteínas Inhibidoras de la Apoptosis/metabolismo , Meduloblastoma/tratamiento farmacológico , Monocitos/citología , Monocitos/efectos de los fármacos , Monocitos/fisiología , Fragmentos de Péptidos/genética , Fragmentos de Péptidos/metabolismo , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Survivin , Transducción Genética , Proteínas de la Matriz Viral/genética , Proteínas de la Matriz Viral/metabolismoRESUMEN
We present three cases of genetically confirmed Gorlin syndrome with desmoplastic medulloblastoma (DMB) in whom tumor recurred despite standard therapy. One patient was found to have a novel germline missense PTCH1 mutation. Molecular analysis of recurrent tumor using fluorescent in situ hybridization (FISH) revealed PTEN and/ or PTCH1 loss in 2 patients. Whole exome sequencing (WES) of tumor in one patient revealed loss of heterozygosity of PTCH1 and a mutation of GNAS gene in its non-coding 3' -untranslated region (UTR) with corresponding decreased protein expression. While one patient died despite high-dose chemotherapy (HDC) plus stem cell rescue (ASCR) and palliative radiotherapy, two patients are currently alive for 18+ and 120+ months respectively following retrieval therapy that did not include irradiation. Infants with DMB and GS should be treated aggressively with chemotherapy at diagnosis to prevent relapse but radiotherapy should be avoided. The use of molecular prognostic markers for DMB should be routinely used to identify the subset of tumors that might have an aggressive course.