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BACKGROUND: The incidence of early-onset colorectal cancer (EOCRC; diagnosed <50 years of age) is rising globally; however, the causes underlying this trend are largely unknown. CRC has strong genetic and environmental determinants, yet common genetic variants and causal modifiable risk factors underlying EOCRC are unknown. We conducted the first EOCRC-specific genome-wide association study (GWAS) and Mendelian randomization (MR) analyses to explore germline genetic and causal modifiable risk factors associated with EOCRC. PATIENTS AND METHODS: We conducted a GWAS meta-analysis of 6176 EOCRC cases and 65 829 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colorectal Transdisciplinary Study (CORECT), the Colon Cancer Family Registry (CCFR), and the UK Biobank. We then used the EOCRC GWAS to investigate 28 modifiable risk factors using two-sample MR. RESULTS: We found two novel risk loci for EOCRC at 1p34.1 and 4p15.33, which were not previously associated with CRC risk. We identified a deleterious coding variant (rs36053993, G396D) at polyposis-associated DNA repair gene MUTYH (odds ratio 1.80, 95% confidence interval 1.47-2.22) but show that most of the common genetic susceptibility was from noncoding signals enriched in epigenetic markers present in gastrointestinal tract cells. We identified new EOCRC-susceptibility genes, and in addition to pathways such as transforming growth factor (TGF) ß, suppressor of Mothers Against Decapentaplegic (SMAD), bone morphogenetic protein (BMP) and phosphatidylinositol kinase (PI3K) signaling, our study highlights a role for insulin signaling and immune/infection-related pathways in EOCRC. In our MR analyses, we found novel evidence of probable causal associations for higher levels of body size and metabolic factors-such as body fat percentage, waist circumference, waist-to-hip ratio, basal metabolic rate, and fasting insulin-higher alcohol drinking, and lower education attainment with increased EOCRC risk. CONCLUSIONS: Our novel findings indicate inherited susceptibility to EOCRC and suggest modifiable lifestyle and metabolic targets that could also be used to risk-stratify individuals for personalized screening strategies or other interventions.
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Neoplasias Colorretais , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Adulto , Feminino , Humanos , Masculino , Idade de Início , Estudos de Casos e Controles , Neoplasias Colorretais/genética , Neoplasias Colorretais/epidemiologia , Polimorfismo de Nucleotídeo Único , Fatores de RiscoRESUMO
A uniparental disomy (UPD) screen using whole genome sequencing (WGS) data from 164 trios with rare disorders in the Irish population was performed to identify large runs of homozygosity of uniparental origin that may harbour deleterious recessive variants. Three instances of whole chromosome uniparental isodisomy (UPiD) were identified: one case of maternal isodisomy of chromosome 1 and two cases of paternal isodisomy of chromosome 2. We identified deleterious homozygous variants on isodisomic chromosomes in two probands: a novel p (Glu59ValfsTer20) variant in TMCO1, and a p (Pro222Leu) variant in PRKRA, respectively. The overall prevalence of whole chromosome UPiD in our cohort was 1 in 55 births, compared to 1 in â¼7,500 births in the general population, suggesting a higher frequency of UPiD in rare disease cohorts. As a distinct mechanism underlying homozygosity compared to biallelic inheritance, the identification of UPiD has important implications for family planning and cascade testing. Our study demonstrates that UPD screening may improve diagnostic yields by prioritising UPiD chromosomes during WGS analysis.
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BACKGROUND: Prolonged sitting time is a risk factor for chronic disease, yet recent global surveillance is not well described. The aims were to clarify: (i) the countries that have collected country-level data on self-reported sitting time; (ii) the single-item tools used to collect these data; and (iii) the duration of sitting time reported across low- to high-income countries. METHODS: Country-level data collected within the last 10 years using single-item self-report were included. The six-stage methodology: (1) reviewing Global Observatory for Physical Activity! Country Cards; (2-4) country-specific searches of PubMed, the Demographic and Health Survey website and Google; (5) analysing the Eurobarometer 88.4; and (6) country-specific searches for World Health Organization STEPwise reports. RESULTS: A total of 7641 records were identified and screened for eligibility. Sixty-two countries (29%) reported sitting time representing 47% of the global adult population. The majority of data were from high-income (61%) and middle income (29%) countries. The tools used were the International Physical Activity Questionnaire (IPAQ; n = 34), a modified IPAQ (n = 1) or the Global Physical Activity Questionnaire (GPAQ; n = 27). The median of mean daily sitting times was 4.7 (IQR: 3.5-5.1) hours across all countries. Higher-income countries recorded a longer duration of sitting time than lower-income countries (4.9 vs 2.7 h). CONCLUSIONS: This study provides an updated collation of countries collecting self-reported sitting time data. The daily sitting time findings should be interpreted cautiously. Current surveillance of sitting time is limited by a lack of coverage. Measures of population sitting time that are valid, feasible and sensitive to change should be embedded within global surveillance systems, to help guide future policy, research and practice. TRIAL REGISTRATION: Not applicable.
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Exercício Físico , Saúde Global , Comportamento Sedentário , Postura Sentada , Feminino , Humanos , Renda , Masculino , Pobreza , Autorrelato , Inquéritos e Questionários , Fatores de TempoRESUMO
BACKGROUND: Physical activity has beneficial effects on the health of cancer survivors. We aimed to investigate accelerometer-assessed physical activity and sedentary time in cancer survivors, and describe activity profiles. Additionally, we identify demographic and clinical correlates of physical activity, sedentary time and activity profiles. METHODS: Accelerometer, questionnaire and clinical data from eight studies conducted in four countries (n = 1447) were pooled. We calculated sedentary time and time spent in physical activity at various intensities using Freedson cut-points. We used latent profile analysis to identify activity profiles, and multilevel linear regression analyses to identify demographic and clinical variables associated with accelerometer-assessed moderate to vigorous physical activity (MVPA), sedentary time, the highly active and highly sedentary profile, adjusting for confounders identified using a directed acyclic graph. RESULTS: Participants spent on average 26 min (3%) in MVPA and 568 min (66%) sedentary per day. We identified six activity profiles. Older participants, smokers and participants with obesity had significantly lower MVPA and higher sedentary time. Furthermore, men had significantly higher MVPA and sedentary time than women and participants who reported less fatigue had higher MVPA time. The highly active profile included survivors with high education level and normal body mass index. Haematological cancer survivors were less likely to have a highly active profile compared to breast cancer survivors. The highly sedentary profile included older participants, males, participants who were not married, obese, smokers, and those < 12 months after diagnosis. CONCLUSIONS: Cancer survivors engage in few minutes of MVPA and spend a large proportion of their day sedentary. Correlates of MVPA, sedentary time and activity profiles can be used to identify cancer survivors at risk for a sedentary and inactive lifestyle.
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Sobreviventes de Câncer/estatística & dados numéricos , Exercício Físico , Comportamento Sedentário , Acelerometria , Estudos de Coortes , Feminino , Monitores de Aptidão Física , Humanos , MasculinoRESUMO
OBJECTIVES: To examine the association of sedentary behavior (SB) with metabolic syndrome (MetS) in adults, as well as to identify the impact of physical inactivity and economic condition on such association. STUDY DESIGN: This is a cross-sectional study. METHODS: This study was conducted in the city of Bauru, São Paulo State, Brazil (n = 970). Television (TV) viewing and physical activity (PA) were assessed by questionnaire. MetS was assessed via medical records. Descriptive statistics and binary logistic regression were used in data analyses. RESULTS: Participants with moderate TV viewing were associated with MetS when compared with low TV viewing group, even after adjustments for age, sex, economic status, smoking, and PA (odds ratio [OR] = 1.49 [95% confidence interval {CI}: 1.01-2.20]). The fully adjusted model showed an association between high exposure to TV viewing with MetS (OR = 1.77 [95%CI: 1.11-2.82]). The combination of physical inactivity and high TV viewing boosted the likelihood of having MetS (OR = 1.89 [95%CI: 1.08-3.29]). CONCLUSION: The results of the present study suggest that moderate and high TV viewing time is associated with the presence of MetS, mainly in insufficiently active adults and those living in lower economic condition.
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Síndrome Metabólica/epidemiologia , Comportamento Sedentário , Idoso , Brasil/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores Socioeconômicos , Inquéritos e Questionários , Televisão/estatística & dados numéricosRESUMO
Multi-drug-resistant Gram-negative organisms (MDRGNO) are an emerging global threat, reflected in the increasing incidence of infections in Ireland and elsewhere. The response to this threat has been the development of Infection Prevention and Control (IPC) guidelines. A survey of IPC teams in Ireland was undertaken to assess compliance with national guidelines. To place these survey results in context, IPC guidelines from the Irish Health Protection Surveillance Centre (HPSC) are compared with guidelines from Healthcare Infection Society (HIS), European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and Centre for Disease Control (CDC). Thirty-three percent of hospitals responded across a range of hospital types. The results highlight the variability in implementation of guidelines across Ireland, as well as the variability between guidelines internationally. Respondents are less than 90% compliant with the majority of MDRGNO screening guidelines. Hospitals have variable access to isolation facilities with an average of 29% single rooms available (range 2.6-100%), resulting in some patients with MDRGNO not being isolated. Broad variability in application of guidance on personal protective equipment was demonstrated. This survey gives an insight into the real-life applicability of HPSC guidelines. Survey results are placed in context with a comparison of five MDRGNO IPC guidelines. Although core tenets of IPC are standard across guidelines, research into which practices are efficient in reducing MDRGNO transmission while being cost-effective would be worthwhile.
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Transmissão de Doença Infecciosa/prevenção & controle , Farmacorresistência Bacteriana Múltipla , Infecções por Bactérias Gram-Negativas/prevenção & controle , Infecções por Bactérias Gram-Negativas/transmissão , Fidelidade a Diretrizes/estatística & dados numéricos , Controle de Infecções/métodos , Guias de Prática Clínica como Assunto , Infecção Hospitalar/prevenção & controle , Infecção Hospitalar/transmissão , Política de Saúde , Pesquisa sobre Serviços de Saúde , Humanos , Irlanda , Inquéritos e QuestionáriosRESUMO
Due to a typesetting error the wrong Table 2 was used. The correct Table 2 is shown here.
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Magnetic clouds (MCs) are transient magnetic structures giving the strongest southward magnetic field (Bz south) in the solar wind. The sheath regions of MCs may also carry a southward magnetic field. The southward magnetic field is responsible for space-weather disturbances. We report a comprehensive analysis of MCs and Bz components in their sheath regions for 1995 to 2017. 85% of 303 MCs contain a south Bz up to 50 nT. Sheath Bz during the 23 years may reach as high as 40 nT. MCs of the strongest magnetic magnitude and Bz south occur in the declining phase of the solar cycle. Bipolar MCs depend on the solar cycle in their polarity, but not in the occurrence frequency. Unipolar MCs show solar-cycle dependence in their occurrence frequency, but not in their polarity. MCs with the highest speeds, the largest total- B magnitudes, and sheath Bz south originate from source regions closer to the solar disk center. About 80% of large Dst storms are caused by MC events. Combinations of a south Bz in the sheath and south-first MCs in close succession have caused the largest storms. The solar-cycle dependence of bipolar MCs is extended to 2017 and now spans 42 years. We find that the bipolar MC Bz polarity solar-cycle dependence is given by MCs that originated from quiescent filaments in decayed active regions and a group of weak MCs of unclear sources, while the polarity of bipolar MCs with active-region flares always has a mixed Bz polarity without solar-cycle dependence and is therefore the least predictable for Bz forecasting. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11207-018-1356-8) contains supplementary material, which is available to authorized users.
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OBJECTIVES: To describe the spectrum of movement disorders and cerebrospinal fluid (CSF) neurotransmitter profiles in paediatric patients with POLG disease. METHODS: We identified children with genetically confirmed POLG disease, in whom CSF neurotransmitter analysis had been undertaken. Clinical data were collected retrospectively. CSF neurotransmitter levels were compared to both standardised age-related reference ranges and to non-POLG patients presenting with status epilepticus. RESULTS: Forty-one patients with POLG disease were identified. Almost 50% of the patients had documented evidence of a movement disorder, including non-epileptic myoclonus, choreoathetosis and ataxia. CSF neurotransmitter analysis was undertaken in 15 cases and abnormalities were seen in the majority (87%) of cases tested. In many patients, distinctive patterns were evident, including raised neopterin, homovanillic acid and 5-hydroxyindoleacetic acid levels. CONCLUSIONS: Children with POLG mutations can manifest with a wide spectrum of abnormal movements, which are often prominent features of the clinical syndrome. Underlying pathophysiology is probably multifactorial, and aberrant monoamine metabolism is likely to play a role.
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Doenças Mitocondriais/líquido cefalorraquidiano , Transtornos dos Movimentos/etiologia , Neurotransmissores/líquido cefalorraquidiano , Adolescente , Criança , Pré-Escolar , DNA Polimerase gama/genética , Feminino , Ácido Homovanílico/líquido cefalorraquidiano , Humanos , Ácido Hidroxi-Indolacético/líquido cefalorraquidiano , Lactente , Masculino , Doenças Mitocondriais/genética , Mutação , Neopterina/líquido cefalorraquidiano , Estudos RetrospectivosRESUMO
OBJECTIVE: Patient-provider communication has been found to be less patient centred, on average, with patients who are members of stigmatized or minority groups. Obesity is a stigmatized condition, and thus, people with obesity may experience less patient-centred communication (PCC). The objective of this study was to assess the association between patient body mass index (BMI) and self-reported quality of PCC experienced over a 12-month period and whether that relationship differed for men and women. METHODS: Data collected for the National Cancer Institute's Health Information National Trends Survey were analysed. Respondents who reported a BMI ≥ 18.5 kg/m2 and indicated having seen a healthcare provider outside of an emergency room in the last 12 months were included. PCC was measured using a validated six-item scale. Multivariate logistic regression was used to model the odds of reporting PCC greater than the sample median. RESULTS: Compared with people with normal weight BMIs, no associations were found between overweight (odds ratio [OR] = 0.84, p = 0.17), class I & II obesity (OR = 0.94, p = 0.68) or class III obesity (OR = 0.86, p = 0.47) and PCC. There was a significant interaction (p = 0.015) such that for men, but not women, higher BMI was associated with less PCC. CONCLUSION: Unlike evidence that women experience more weight stigma, in the healthcare domain, men may be at elevated risk of experiencing communication influenced by weight stigma.
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OBJECTIVE: Community-based, family-centered obesity prevention/treatment initiatives have been shown to be effective in reducing body mass index (BMI) and improving healthy habits in children if implemented with high intensity and sufficient duration. Let's Go! 5-2-1-0 Program (5-2-1-0) was incorporated into family-centered, monthly physical activity classes and cooking classes over six months delivered by Young Men's Christian Association (YMCA) staff. We hypothesized that implementation of this intervention would improve 5-2-1-0 knowledge attainment, increase healthy behavior (based on 5- 2-1-0 curriculum), and improve BMI and waist circumference measurements in children. METHODS: Children attending YMCA summer camps in Rochester, MN, during 2016 were recruited via study packets mailed to their families. Height, weight, and waist circumference measurements as well as the results of the Modified Healthy Habits Survey and the 5-2-1-0 Knowledge Acquisition Survey were recorded for each participating child at baseline and 6-month follow-up. The intervention group received monthly healthy habit reminder emails, and was invited to monthly evening cooking and physical activity classes for 7 sessions over a 6-month period. RESULTS: Fifteen families in the intervention group attended classes. Of those, 13 families regularly participated in (attended at least 5 out of 7) both the monthly physical activity and cooking classes. The children in the intervention group had a significant improvement in the number of Knowledge Acquisition Survey questions answered correctly (p<0.001), while there was no improvement in the control group. As compared to children in the control group, there was no significant change in BMI or waist circumference or healthy habits in the intervention group. CONCLUSION: Our study findings indicate that our intervention resulted in improved knowledge about healthy habits, but did not significantly impact healthy habits or BMI. Potential reasons for this were the small sample size and the attenuated length and/or intensity of the intervention.
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Pathogenic COL4A2 variants cause abnormalities in collagen production and can have serious implications for a range of organ systems, most notably the brain. Herein, we describe a large family of first-degree relatives affected by a novel heterozygous variant in COL4A2 (c.3490G.A). A wide disease spectrum is described, from asymptomatic to symptomatic, including 2 children with porencephaly and co-existing juvenile idiopathic polyarthritis. During a subsequent pregnancy, antenatal testing identified a positive fetus. In view of the literature, we review management and genetic counselling dilemmas.
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Artrite Juvenil/genética , Colágeno Tipo IV/genética , Colágeno/metabolismo , Porencefalia/genética , Artrite Juvenil/complicações , Artrite Juvenil/fisiopatologia , Doenças do Desenvolvimento Ósseo , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Colágeno/biossíntese , Colágeno/genética , Anormalidades Craniofaciais , Feminino , Heterozigoto , Humanos , Hiperostose , Hipertelorismo , Masculino , Mutação , Linhagem , Fenótipo , Porencefalia/complicações , Porencefalia/fisiopatologiaRESUMO
The affine transformation hypothesis is usually adopted in order to link the tissue scale with the fibers scale in structural constitutive models of fibrous tissues. Thanks to the recent advances in imaging techniques, such as multiphoton microscopy, the microstructural behavior and kinematics of fibrous tissues can now be monitored at different stretching within the same sample. Therefore, the validity of the affine hypothesis can be investigated. In this paper, the fiber reorientation predicted by the affine assumption is compared to experimental data obtained during mechanical tests on skin and liver capsule coupled with microstructural imaging using multiphoton microscopy. The values of local strains and the collagen fibers orientation measured at increasing loading levels are used to compute a theoretical estimation of the affine reorientation of collagen fibers. The experimentally measured reorientation of collagen fibers during loading could not be successfully reproduced with this simple affine model. It suggests that other phenomena occur in the stretching process of planar fibrous connective tissues, which should be included in structural constitutive modeling approaches.
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Colágeno/fisiologia , Modelos Biológicos , Fenômenos Biomecânicos , Humanos , Fígado/citologia , Fígado/metabolismo , Pele/citologia , Pele/metabolismo , Estresse MecânicoRESUMO
Acute Flaccid Paralysis (AFP) surveillance, including case investigation and specimen collection is a gold standard method for poliomyelitis surveillance. The expected annual non-polio AFP rate <15 years of age in Ireland is = 1/100 000 population. This study reviewed all cases of AFP reported to the Irish Paediatric Surveillance Unit and the Health Protection Surveillance Centre between January 2009 and December 2014 and compared reporting rates with the expected incidence rate annually. We assessed quality of surveillance data in terms of completeness of investigation for each case reported. Forty-three AFP cases in children <15 years were notified; 35 of which were confirmed. Guillain-Barre Syndrome (GBS) accounted for 48.6% (n=17) of AFP notifications. In 2014, the expected annual AFP target rate was reached. This study identified possible under-reporting of AFP paediatric cases in Ireland between 2009-2013. Completeness of investigations has improved over time, but requires further work.
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AIMS: In an era when clinical microbiology laboratories are under increasing financial pressure, there is a need for inexpensive, yet effective, rapid microbiology tests. The aim of this study was to evaluate a novel modification of standard methodology for the identification and antimicrobial susceptibility testing (AST) of pathogens in positive blood cultures, reducing the turnaround time of laboratory results by 24â h. METHODS: 277 positive blood cultures had a Gram stain performed and were subcultured and incubated at 37°C in a CO2 atmosphere for 4-6â h. Identification of the visible growth was performed using matrix-assisted laser desorption time of flight mass spectrometry (MALDI-TOF MS). Taking a modified approach to the Clinical and Laboratory Standards Institute-standardised AST methodology, an inoculum density of 0.5 McFarland was prepared from the early growth for disc diffusion testing. The standard AST method was also performed on the 18-24â h culture. RESULTS: 96% (n=73/76) of gram-negative organisms were correctly identified by MALDI-TOF MS. Comparative analysis of the rapid and standard AST results showed an overall interpretive category error rate of 7.7% (6.7% minor errors, 0.6% major errors and 0.4% very major errors). 100% of Staphylococcus aureus (n=41) and enterococcus isolates (n=9) were correctly identified after 4-6â h incubation. The overall AST categorical agreement was also 100% for these isolates. CONCLUSIONS: An incubation of 4-6â h directly from positive blood cultures allowed for both a rapid species identification and an antimicrobial susceptibility result approximately 24â h earlier than is possible using standard methodology.
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FIKK kinases are a novel family of kinases unique to the Apicomplexa. While most apicomplexans encode a single FIKK kinase, Plasmodium falciparum expresses 21 and piroplasms do not encode a FIKK kinase. FIKK kinases share a conserved C-terminal catalytic domain, but the N-terminal region is highly variable and contains no known functional domains. To date, FIKK kinases have been primarily studied in P. falciparum and Plasmodium berghei. Those that have been studied are exported from the parasite and associate with diverse locations in the infected erythrocyte cytosol or membrane. Deletion of individual P. falciparum FIKK kinases indicates that they may play a role in modification of the infected erythrocyte. The current study characterises the single FIKK gene in Toxoplasma gondii to evaluate the importance of the FIKK kinase in an apicomplexan that has a single FIKK kinase. The TgFIKK gene encoded a protein of approximately 280kDa. Endogenous tagging of the FIKK protein with Yellow Fluorescent Protein showed that the FIKK protein exclusively localised to the posterior end of tachyzoites. A Yellow Fluorescent Protein-tagged FIKK and a Ty-tagged FIKK both co-localised with T. gondii membrane occupation and recognition nexus protein to the basal complex and were localised apical to inner membrane complex protein-5 and Centrin2. Deletion of TgFIKK, surprisingly, had no detectable effect on the parasite's lytic cycle in vitro in human fibroblast cells or in acute virulence in vivo. Thus, our results clearly show that while the FIKK kinase is expressed in tachyzoites, it is not essential for the lytic cycle of T. gondii.
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Fosfotransferases/metabolismo , Toxoplasma/enzimologia , Processamento Alternativo , Animais , Apicomplexa/enzimologia , Western Blotting , Linhagem Celular , Biologia Computacional , DNA Complementar/química , Feminino , Imunofluorescência , Deleção de Genes , Regulação Enzimológica da Expressão Gênica , Humanos , Isoenzimas/química , Isoenzimas/genética , Isoenzimas/metabolismo , Isoleucina , Lisina , Camundongos , Camundongos Endogâmicos C57BL , Fenilalanina , Fosfotransferases/química , Fosfotransferases/genética , RNA Mensageiro/genética , RNA Mensageiro/isolamento & purificação , RNA de Protozoário/genética , RNA de Protozoário/isolamento & purificação , Toxoplasma/genética , Toxoplasma/metabolismo , Toxoplasma/patogenicidade , Toxoplasmose Animal/parasitologia , VirulênciaRESUMO
Observations of coronal jets increasingly suggest that local fragmentation and intermittency play an important role in the dynamics of these events. In this work we investigate this fragmentation in high-resolution simulations of jets in the closed-field corona. We study two realizations of the embedded-bipole model, whereby impulsive helical outflows are driven by reconnection between twisted and untwisted field across the domed fan plane of a magnetic null. We find that the reconnection region fragments following the onset of a tearing-like instability, producing multiple magnetic null points and flux-rope structures within the current layer. The flux ropes formed within the weak-field region in the center of the current layer are associated with "blobs" of density enhancement that become filamentary threads as the flux ropes are ejected from the layer, whereupon new flux ropes form behind them. This repeated formation and ejection of flux ropes provides a natural explanation for the intermittent outflows, bright blobs of emission, and filamentary structure observed in some jets. Additional observational signatures of this process are discussed. Essentially all jet models invoke reconnection between regions of locally closed and locally open field as the jet-generation mechanism. Therefore, we suggest that this repeated tearing process should occur at the separatrix surface between the two flux systems in all jets. A schematic picture of tearing-mediated jet reconnection in three dimensions is outlined.
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MELAS is a rare mitochondrial disorder. We report two cases in Irish males where the characteristics were evident, but the diagnosis not made for a considerable period of time. In one of the cases the symptoms were presumed secondary to prematurity. In the other the symptoms were presumed secondary to epilepsy and he had three respiratory arrests secondary to benzodiazepine administration. This report wishes to highlight MELAS as a differential diagnosis in paediatric patients who present with stroke.
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Síndrome MELAS/diagnóstico , Diagnóstico Tardio , Diagnóstico Diferencial , Epilepsia/complicações , Humanos , Recém-Nascido , Recém-Nascido Prematuro , MasculinoRESUMO
Potential health benefits have been attributed to broccoli consumption. Hence, there is potential for use of broccoli seed extract (BSE) in food or for use as a dietary supplement. To assess the potential safety of a BSE product, three genotoxicity experiments, including an Ames, in vivo mouse micronucleus, and in vivo mouse sperm abnormality assay, were carried out. BSE was subject to an acute oral toxicity test and was evaluated in a 30-day feeding study in rats. BSE showed no mutagenic activity in the Ames assay and no evidence of genotoxic potential in the in vivo assays at doses up to 10 g/kg body weight (bw). The LD50 of BSE in rats was >10 g/kg bw/d. In the 30-day feeding study, in which BSE was administered in the diet to provide doses of 0, 0.3, 1.0, or 3.0 g/kg bw/d, no toxicological significant effects were noted on body weight, body weight gain, organ weights, or on the results of hematological, clinical chemistry and histopathological evaluations. The no-observed-adverse-effect level was considered to be 3.0 g/kg bw/d, the highest dose tested. Collectively, these results support the safe use of BSE as a food ingredient or product.