53 research outputs found
Analysis of Major Histocompatibility Antigens and the Mononuclear Cell Infiltrate in Halo Nevi
A series of monoclonal antibodies was used to characterize the nevomelanocytes and the inflammatory infiltrate of 11 halo nevi in different stages of resolution, employing an immunoperoxidase technique. Three of the 11 halo nevi histologically showed signs of mild or moderate nevomelanocytic atypia. It was found that the vast majority of the nevomelanocytes in halo nevi with a dense inflammatory infiltrate markedly expressed HLA-A,B,C antigens, while expression was not demonstrable in nevocellular nests not adjacent to the mononuclear infiltrate. No difference in expression of HLA-A,B,C antigens was found between the 3 cases with mild or moderate nevomelanocytic atypia and the other eases lacking atypia. Expression of HLA-DR (Ia-like) antigens was found on few nevomelanocytes in only 2 of 11 lesions. The cellular composition of the mononuclear inflammatory infiltrate showed a predominance of T cells (80% or more) with a relatively high proportion of cytotoxic/suppressor T cells. Most of the T cells showed signs of activation as judged by staining for HLA-DR antigens. These results demonstrate that the expression of HLA- A,B,C antigens on the nevomelanocytes and the cellular composition of the mononuclear inflammatory infiltrate in halo nevi are very similar to that in malignant melanomas and dysplastic nevi. These findings also indicate that the expression of HLA-A,B,C antigens on nevomelanocytes is primarily dependent on the presence of T- cell immune response and not necessarily related to the presence of nevomelanocytic atypia
Skin examination behavior: the role of melanoma history, skin type, psychosocial factors, and region of residence in determining clinical and self-conducted skin examination
Objective: To examine the frequency and correlates of skin examination behaviors in an international sample of individuals at varying risk of developing melanoma. Design: A cross-sectional, web-based survey. Setting: Data were collected from the general population over a 20-month period on behalf of the Melanoma Genetics Consortium (GenoMEL). Participants: A total of 8178 adults from Northern (32%), Central (33%), and Southern (14%) Europe, Australia (13%), and the United States (8%). Main outcome measures: Self-reported frequency of skin self-examination (SSE) and clinical skin examination (CSE). Results: After adjustment for age and sex, frequency of skin examination was higher in both Australia (odds ratio [OR]SSE=1.80 [99% CI, 1.49-2.18]; ORCSE=2.68 [99% CI, 2.23-3.23]) and the United States (ORSSE=2.28 [99% CI, 1.76-2.94]; ORCSE=3.39 [99% CI, 2.60-4.18]) than in the 3 European regions combined. Within Europe, participants from Southern Europe reported higher rates of SSE than those in Northern Europe (ORSSE=1.61 [99% CI, 1.31-1.97]), and frequency of CSE was higher in both Central (ORCSE=1.47 [99% CI, 1.22-1.78]) and Southern Europe (ORCSE=3.46 [99% CI, 2.78, 4.31]) than in Northern Europe. Skin examination behavior also varied according to melanoma history: participants with no history of melanoma reported the lowest levels of skin examination, while participants with a previous melanoma diagnosis reported the highest levels. After adjustment for region, and taking into account the role of age, sex, skin type, and mole count, engagement in SSE and CSE was associated with a range of psychosocial factors, including perceived risk of developing melanoma; perceived benefits of, and barriers to, skin examination; perceived confidence in one's ability to engage in screening; and social norms. In addition, among those with no history of melanoma, higher cancer-related worry was associated with greater frequency of SSE. Conclusions: Given the strong association between psychosocial factors and skin examination behaviors, particularly among people with no history of melanoma, we recommend that greater attempts be made to integrate psycho-education into the fabric of public health initiatives and clinical care, with clinicians, researchers, and advocacy groups playing a key role in guiding individuals to appropriate tools and resources
GNAQ and GNA11 mutations and downstream YAP activation in choroidal nevi
Background: Mutations in GNAQ/11 genes are considered an early event in the development of uveal melanoma that may derive from a pre-existing nevus. The Hippo pathway, by way of YAP activation, rather than MAP kinase, has a role in the oncogenic capacity of GNAQ/11 mutations.Methods: We investigated 16 nevi from 13 human eyes for driver GNAQ/11 mutations using droplet digital PCR and determined whether nevi are clonal by quantifying mutant nevus cell fractions. Immunohistochemistry was performed on 15 nevi to analyse YAP activation.Results: For 15 out of 16 nevi, a GNAQ/11 mutation was detected in the nevus cells albeit at a low frequency with a median of 13%. Nuclear YAP, a transcriptional co-activator in the Hippo tumour-suppressor pathway, was detected in 14/15 nevi.Conclusions: Our analysis suggests that a mutation in GNAQ/11 occurs in a subset of choroidal nevus cells. We hypothesise that GNAQ/11 mutant-driven extracellular mitogenic signalling involving YAP activation leads to accumulation of wild-type nevus cells
Phenotypic and Histopathological Tumor Characteristics According to CDKN2A Mutation Status among Affected Members of\ua0Melanoma Families
Substance use risk profiles and associations with early substance use in adolescence
We examined whether anxiety sensitivity, hopelessness, sensation seeking, and impulsivity (i.e., revised version of the Substance Use Risk Profile Scale) would be related to the lifetime prevalence and age of onset of alcohol, tobacco, and cannabis use, and to polydrug use in early adolescence. Baseline data of a broader effectiveness study were used from 3,783 early adolescents aged 11â15Â years. Structural equation models showed that hopelessness and sensation seeking were indicative of ever-used alcohol, tobacco or cannabis and for the use of more than one substance. Furthermore, individuals with higher levels of hopelessness had a higher chance of starting to use alcohol or cannabis at an earlier age, but highly anxiety sensitive individuals were less likely to start using alcohol use at a younger age. Conclusively, early adolescents who report higher levels of hopelessness and sensation seeking seem to be at higher risk for an early onset of substance use and poly substance use
Contribution of chronic diseases to the disability burden in a population 15Â years and older, Belgium, 1997â2008
Particulate matter exposure during pregnancy is associated with birth weight, but not gestational age, 1962-1992: a cohort study
<p>Abstract</p> <p>Background</p> <p>Exposure to air pollutants is suggested to adversely affect fetal growth, but the evidence remains inconsistent in relation to specific outcomes and exposure windows.</p> <p>Methods</p> <p>Using birth records from the two major maternity hospitals in Newcastle upon Tyne in northern England between 1961 and 1992, we constructed a database of all births to mothers resident within the city. Weekly black smoke exposure levels from routine data recorded at 20 air pollution monitoring stations were obtained and individual exposures were estimated via a two-stage modeling strategy, incorporating temporally and spatially varying covariates. Regression analyses, including 88,679 births, assessed potential associations between exposure to black smoke and birth weight, gestational age and birth weight standardized for gestational age and sex.</p> <p>Results</p> <p>Significant associations were seen between black smoke and both standardized and unstandardized birth weight, but not for gestational age when adjusted for potential confounders. Not all associations were linear. For an increase in whole pregnancy black smoke exposure, from the 1<sup>st </sup>(7.4 ÎŒg/m<sup>3</sup>) to the 25<sup>th </sup>(17.2 ÎŒg/m<sup>3</sup>), 50<sup>th </sup>(33.8 ÎŒg/m<sup>3</sup>), 75<sup>th </sup>(108.3 ÎŒg/m<sup>3</sup>), and 90<sup>th </sup>(180.8 ÎŒg/m<sup>3</sup>) percentiles, the adjusted estimated decreases in birth weight were 33 g (SE 1.05), 62 g (1.63), 98 g (2.26) and 109 g (2.44) respectively. A significant interaction was observed between socio-economic deprivation and black smoke on both standardized and unstandardized birth weight with increasing effects of black smoke in reducing birth weight seen with increasing socio-economic disadvantage.</p> <p>Conclusions</p> <p>The findings of this study progress the hypothesis that the association between black smoke and birth weight may be mediated through intrauterine growth restriction. The associations between black smoke and birth weight were of the same order of magnitude as those reported for passive smoking. These findings add to the growing evidence of the harmful effects of air pollution on birth outcomes.</p
Problematic school absenteeism:The voice of the school staff
I Sverige omfattas alla elever frĂ„n förskoleklass till Ă„rskurs nio av skolplikt, men Ă€ndĂ„ har mĂ„nga elever hög frĂ„nvaro. Problematisk skolfrĂ„nvaro Ă€r ett globalt samhĂ€llsproblem som kan ge allvarliga konsekvenser för eleven bĂ„de nu och i framtiden, vilket dessutom leder till stora samhĂ€llskostnader. Syftet med denna studie Ă€r att undersöka hur yrkesverksamma inom skolan beskriver och upplever utmaningar och möjligheter i arbetet med problematisk skolfrĂ„nvaro. Detta har gjorts genom semistrukturerade intervjuer med olika aktörer i skolan som aktivt arbetar med frĂ„gan: rektor, specialpedagog och socionom i skolan. Intervjuerna har analyserats med hjĂ€lp av innehĂ„llsanalys och Bronfenbrenners ekologiska systemteori. De huvudsakliga utmaningarna som beskrevs vid intervjuerna var brist pĂ„ ekonomiska och materiella resurser, organisatoriska hinder, tid och svĂ„righeter att bygga en god relation till elev och vĂ„rdnadshavare. De övergripande förutsĂ€ttningarna och möjligheterna som beskrevs var tidig kartlĂ€ggning och insatser, god relation och allians med elev och vĂ„rdnadshavare, helhetsperspektiv, samverkan med socialtjĂ€nst samt nĂ€rvarokultur pĂ„ skolan. Resultatet av studien visade dessutom att de skolor med professionen âsocionom i skolanâ hade större utrymme för att arbeta uppsökande med elever med problematisk skolfrĂ„nvaro, nĂ„got som de skolor utan denna resurs beskrev som nĂ„got de saknade. UtifrĂ„n Bronfenbrenners ekologiska systemteori Ă€r det tydligt att arbetet med problematisk skolfrĂ„nvaro Ă€r komplext och grĂ€nsöverskridande samt behöver förstĂ„s ur ett större perspektiv Ă€n skolans fyra vĂ€ggar. Teorin tydliggör hur elevens olika nĂ€tverk, miljöer, skeenden och samhĂ€lleliga kontext pĂ„verkar dennes skolsituation och attityd gentemot den. Slutligen relateras studiens resultat till teorin samt tidigare forskning som tillsammans pekar pĂ„ att problematisk skolfrĂ„nvaro Ă€r ett vĂ€xande problem, att det kan leda till allvarliga konsekvenser samt att arbetet Ă€r relationellt och behöver förstĂ„s ur ett helhetsperspektiv
Problematic school absenteeism:The voice of the school staff
I Sverige omfattas alla elever frĂ„n förskoleklass till Ă„rskurs nio av skolplikt, men Ă€ndĂ„ har mĂ„nga elever hög frĂ„nvaro. Problematisk skolfrĂ„nvaro Ă€r ett globalt samhĂ€llsproblem som kan ge allvarliga konsekvenser för eleven bĂ„de nu och i framtiden, vilket dessutom leder till stora samhĂ€llskostnader. Syftet med denna studie Ă€r att undersöka hur yrkesverksamma inom skolan beskriver och upplever utmaningar och möjligheter i arbetet med problematisk skolfrĂ„nvaro. Detta har gjorts genom semistrukturerade intervjuer med olika aktörer i skolan som aktivt arbetar med frĂ„gan: rektor, specialpedagog och socionom i skolan. Intervjuerna har analyserats med hjĂ€lp av innehĂ„llsanalys och Bronfenbrenners ekologiska systemteori. De huvudsakliga utmaningarna som beskrevs vid intervjuerna var brist pĂ„ ekonomiska och materiella resurser, organisatoriska hinder, tid och svĂ„righeter att bygga en god relation till elev och vĂ„rdnadshavare. De övergripande förutsĂ€ttningarna och möjligheterna som beskrevs var tidig kartlĂ€ggning och insatser, god relation och allians med elev och vĂ„rdnadshavare, helhetsperspektiv, samverkan med socialtjĂ€nst samt nĂ€rvarokultur pĂ„ skolan. Resultatet av studien visade dessutom att de skolor med professionen âsocionom i skolanâ hade större utrymme för att arbeta uppsökande med elever med problematisk skolfrĂ„nvaro, nĂ„got som de skolor utan denna resurs beskrev som nĂ„got de saknade. UtifrĂ„n Bronfenbrenners ekologiska systemteori Ă€r det tydligt att arbetet med problematisk skolfrĂ„nvaro Ă€r komplext och grĂ€nsöverskridande samt behöver förstĂ„s ur ett större perspektiv Ă€n skolans fyra vĂ€ggar. Teorin tydliggör hur elevens olika nĂ€tverk, miljöer, skeenden och samhĂ€lleliga kontext pĂ„verkar dennes skolsituation och attityd gentemot den. Slutligen relateras studiens resultat till teorin samt tidigare forskning som tillsammans pekar pĂ„ att problematisk skolfrĂ„nvaro Ă€r ett vĂ€xande problem, att det kan leda till allvarliga konsekvenser samt att arbetet Ă€r relationellt och behöver förstĂ„s ur ett helhetsperspektiv
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