For a comprehensive overview of the genetic alterations of neuroblastoma, their association and clinical significance, we conducted a whole-genome DNA copy number analysis. PATIENTS AND METHODS: A series of 493 neuroblastoma (NB) samples was investigated by array-based comparative genomic hybridization in two consecutive steps (224, then 269 patients). RESULTS: Genomic analysis identified several types of profiles. Tumors presenting exclusively whole-chromosome copy number variations were associated with excellent survival. No disease-related death was observed in this group. In contrast, tumors with any type of segmental chromosome alterations characterized patients with a high risk of relapse. Patients with both numerical and segmental abnormalities clearly shared the higher risk of relapse of segmental-only patients. In a multivariate analysis, taking into account the genomic profile, but also previously described individual genetic and clinical markers with prognostic significance, the presence of segmental alterations with (HR, 7.3; 95% CI, 3.7 to 14.5; P < .001) or without MYCN amplification (HR, 4.5; 95% CI, 2.4 to 8.4; P < .001) was the strongest predictor of relapse; the other significant variables were age older than 18 months (HR, 1.8; 95% CI, 1.2 to 2.8; P = .004) and stage 4 (HR, 1.8; 95% CI, 1.2 to 2.7; P = .005). Finally, within tumors showing segmental alterations, stage 4, age, MYCN amplification, 1p and 11q deletions, and 1q gain were independent predictors of decreased overall survival. CONCLUSION: The analysis of the overall genomic pattern, which probably unravels particular genomic instability mechanisms rather than the analysis of individual markers, is essential to predict relapse in NB patients. It adds critical prognostic information to conventional markers and should be included in future treatment stratification.
- MeSH
- Gene Amplification MeSH
- Survival Analysis MeSH
- DNA, Neoplasm genetics MeSH
- Financing, Organized MeSH
- Genes, myc MeSH
- Infant MeSH
- Humans MeSH
- Multivariate Analysis MeSH
- Biomarkers, Tumor MeSH
- Follow-Up Studies MeSH
- Genomic Instability MeSH
- Neuroblastoma genetics pathology MeSH
- Prognosis MeSH
- Proportional Hazards Models MeSH
- Oligonucleotide Array Sequence Analysis MeSH
- Comparative Genomic Hybridization MeSH
- Check Tag
- Infant MeSH
- Humans MeSH
- Publication type
- Multicenter Study MeSH
- Comparative Study MeSH
... Carskadon, 17 Physiology of Upper and Lower Airways 174 -- William C Dement, and Thomas Roth 5 Sleep ... ... Pigeon and Thomas A. ... ... Brown -- 69 Sleep Medicine Clinical Practice and -- Compliance—Europe 675 -- Thomas Penze! ... ... Van Dongen, Thomas J. Bai kin, and Steven R. ... ... Hursh, Thomas J. Balkin, and Hans P.A. ...
Sixth edition xlv, 1730 stran : ilustrace ; 28 cm
- Conspectus
- Fyziologie člověka a srovnávací fyziologie
- NML Fields
- fyziologie
- NML Publication type
- kolektivní monografie
BackgroundTimely treatment with neuraminidase inhibitors (NAI) can reduce severe outcomes in influenza patients.AimWe assessed the impact of antiviral treatment on in-hospital deaths of laboratory-confirmed influenza patients in 11 European Union countries from 2010/11 to 2019/20.MethodsCase-based surveillance data from hospitalised patients with known age, sex, outcome, ward, vaccination status, timing of antiviral treatment, and hospitalisation were obtained. A mixed effect logistic regression model using country as random intercept was applied to estimate the adjusted odds ratio (aOR) for in-hospital death in patients treated with NAIs vs not treated.ResultsOf 19,937 patients, 31% received NAIs within 48 hours of hospital admission. Older age (60-79 years aOR 3.0, 95% CI: 2.4-3.8; 80 years 8.3 (6.6-10.5)) and intensive care unit admission (3.8, 95% CI: 3.4-4.2) increased risk of dying, while early hospital admission after symptom onset decreased risk (aOR 0.91, 95% CI: 0.90-0.93). NAI treatment initiation within 48 hours and up to 7 days reduced risk of dying (0-48 hours aOR 0.51, 95% CI: 0.45-0.59; 3-4 days 0.59 (0.51-0.67); 5-7 days 0.64 (0.56-0.74)), in particular in patients 40 years and older (e.g. treatment within 48 hours: 40-59 years aOR 0.43, 95% CI: 0.28-0.66; 60-79 years 0.50 (0.39-0.63); ≥80 years 0.51 (0.42-0.63)).ConclusionNAI treatment given within 48 hours and possibly up to 7 days after symptom onset reduced risk of in-hospital death. NAI treatment should be considered in older patients to prevent severe outcomes.
- MeSH
- Antiviral Agents therapeutic use MeSH
- Influenza, Human * drug therapy epidemiology MeSH
- Guanidines therapeutic use MeSH
- Enzyme Inhibitors therapeutic use MeSH
- Humans MeSH
- Hospital Mortality MeSH
- Neuraminidase MeSH
- Oseltamivir * therapeutic use MeSH
- Aged MeSH
- Treatment Outcome MeSH
- Zanamivir therapeutic use MeSH
- Check Tag
- Humans MeSH
- Aged MeSH
- Publication type
- Journal Article MeSH
The faeces of the red fox, Vulpes vulpes (Linnaeus), and the domestic cat, Felis catus (Linnaeus), can be responsible for spreading eggs of Echinococcus multilocularis Leuckart, 1863 and oocysts of Toxoplasma gondii (Nicolle et Manceaux, 1908) into the environment. The accidental ingestion of these eggs or oocysts, through consumption of raw fruits or vegetables grown in or in contact with contaminated soil, can lead to alveolar echinococcosis (AE) or toxoplasmosis in humans. The present study provides a quantitative assessment of the faecal deposition by foxes and cats in kitchen gardens where fruits and vegetables are grown and its consequences for zoonosis transmission. The density of definitive host faeces is considered as one of the main factors in infection risk for intermediate hosts. The density of fox and cat faeces, as well as the prevalence of both AE and toxoplasmosis in rodent populations (contaminated by ingestion of eggs or oocysts), were compared within and outside kitchen gardens. Our results showed that the mean density of fox faeces did not significantly differ between kitchen gardens and habitat edges (0.29 ± 0.04 faeces/m2 vs 0.22 ± 0.02 faeces/m2), the latter being known as an area of high fox faeceal densities. The density of cat faeces was significantly higher within the kitchen garden than outside (0.86 ± 0.22 faeces/m2 vs 0.04 ± 0.02 faeces/m2). The sampled kitchen gardens might therefore be considered as possible hotspots for both fox and cat defecation. Of the 130 rodents trapped, 14% were infected by at least one species of fox or cat intestinal parasite. These rodents were significantly more often infected when they were exposed to a kitchen garden. These results suggest that the deposit of fox and cat faeces in kitchen gardens would significantly impact the risk of human exposure to E. multilocularis and T. gondii. and should be prevented using effective means.
- MeSH
- Arvicolinae * MeSH
- Echinococcus multilocularis isolation & purification MeSH
- Echinococcosis epidemiology parasitology veterinary MeSH
- Feces parasitology MeSH
- Cats MeSH
- Foxes MeSH
- Murinae * MeSH
- Rodent Diseases epidemiology parasitology MeSH
- Prevalence MeSH
- Toxoplasma isolation & purification MeSH
- Toxoplasmosis, Animal epidemiology parasitology MeSH
- Gardens MeSH
- Animals MeSH
- Check Tag
- Cats MeSH
- Male MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- France MeSH
BACKGROUND: An association between low socioeconomic status (SES) and lung cancer has been observed in several studies, but often without adequate control for smoking behavior. We studied the association between lung cancer and occupationally derived SES, using data from the international pooled SYNERGY study. METHODS: Twelve case-control studies from Europe and Canada were included in the analysis. Based on occupational histories of study participants we measured SES using the International Socio-Economic Index of Occupational Status (ISEI) and the European Socio-economic Classification (ESeC). We divided the ISEI range into categories, using various criteria. Stratifying by gender, we calculated odds ratios (OR) and 95% confidence intervals (CI) by unconditional logistic regression, adjusting for age, study, and smoking behavior. We conducted analyses by histological subtypes of lung cancer and subgroup analyses by study region, birth cohort, education and occupational exposure to known lung carcinogens. RESULTS: The analysis dataset included 17,021 cases and 20,885 controls. There was a strong elevated OR between lung cancer and low SES, which was attenuated substantially after adjustment for smoking, however a social gradient persisted. SES differences in lung cancer risk were higher among men (lowest vs. highest SES category: ISEI OR 1.84 (95% CI 1.61-2.09); ESeC OR 1.53 (95% CI 1.44-1.63)), than among women (lowest vs. highest SES category: ISEI OR 1.54 (95% CI 1.20-1.98); ESeC OR 1.34 (95% CI 1.19-1.52)). CONCLUSION: SES remained a risk factor for lung cancer after adjustment for smoking behavior.
- MeSH
- Smoking epidemiology MeSH
- Middle Aged MeSH
- Humans MeSH
- Logistic Models MeSH
- Lung Neoplasms epidemiology pathology MeSH
- Odds Ratio MeSH
- Occupational Exposure MeSH
- Risk Factors MeSH
- Aged MeSH
- Sex Factors MeSH
- Social Class MeSH
- Age Factors MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Meta-Analysis MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Europe MeSH
- Canada MeSH
BACKGROUND: The nature of the association between occupational social prestige, social mobility, and risk of lung cancer remains uncertain. Using data from the international pooled SYNERGY case-control study, we studied the association between lung cancer and the level of time-weighted average occupational social prestige as well as its lifetime trajectory. METHODS: We included 11,433 male cases and 14,147 male control subjects. Each job was translated into an occupational social prestige score by applying Treiman's Standard International Occupational Prestige Scale (SIOPS). SIOPS scores were categorized as low, medium, and high prestige (reference). We calculated odds ratios (OR) with 95 % confidence intervals (CI), adjusting for study center, age, smoking, ever employment in a job with known lung carcinogen exposure, and education. Trajectories in SIOPS categories from first to last and first to longest job were defined as consistent, downward, or upward. We conducted several subgroup and sensitivity analyses to assess the robustness of our results. RESULTS: We observed increased lung cancer risk estimates for men with medium (OR = 1.23; 95 % CI 1.13-1.33) and low occupational prestige (OR = 1.44; 95 % CI 1.32-1.57). Although adjustment for smoking and education reduced the associations between occupational prestige and lung cancer, they did not explain the association entirely. Traditional occupational exposures reduced the associations only slightly. We observed small associations with downward prestige trajectories, with ORs of 1.13, 95 % CI 0.88-1.46 for high to low, and 1.24; 95 % CI 1.08-1.41 for medium to low trajectories. CONCLUSIONS: Our results indicate that occupational prestige is independently associated with lung cancer among men.
- MeSH
- Adult MeSH
- Smoking adverse effects epidemiology MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Lung Neoplasms epidemiology MeSH
- Odds Ratio MeSH
- Occupational Exposure adverse effects MeSH
- Risk Factors MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Social Mobility statistics & numerical data MeSH
- Socioeconomic Factors MeSH
- Case-Control Studies MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
... Howley and Thomas R. Broker xxi -- I. ... ... From Epidermodysplasia Verruciformis Patients and Renal Allograft Recipients -- Herbert Pfister, Thomas ... ... -- Characterization of Transcription Control Regions of the Cottontail Rabbit Papillomavirus -- Isabelle ... ... Faras, and Thomas R. Broker 501 -- IX. ...
UCLA symposia on molecular and cellular biology. New series ; vol. 32
xxii, 575 s. : il., tab. ; 24 cm
BACKGROUND: Evidence is limited regarding risk and the shape of the exposure-response curve at low asbestos exposure levels. We estimated the exposure-response for occupational asbestos exposure and assessed the joint effect of asbestos exposure and smoking by sex and lung cancer subtype in general population studies. METHODS: We pooled 14 case-control studies conducted in 1985-2010 in Europe and Canada, including 17,705 lung cancer cases and 21,813 controls with detailed information on tobacco habits and lifetime occupations. We developed a quantitative job-exposure-matrix to estimate job-, time period-, and region-specific exposure levels. Fiber-years (ff/ml-years) were calculated for each subject by linking the matrix with individual occupational histories. We fit unconditional logistic regression models to estimate odds ratios (ORs), 95% confidence intervals (CIs), and trends. RESULTS: The fully adjusted OR for ever-exposure to asbestos was 1.24 (95% CI, 1.18, 1.31) in men and 1.12 (95% CI, 0.95, 1.31) in women. In men, increasing lung cancer risk was observed with increasing exposure in all smoking categories and for all three major lung cancer subtypes. In women, lung cancer risk for all subtypes was increased in current smokers (ORs ~two-fold). The joint effect of asbestos exposure and smoking did not deviate from multiplicativity among men, and was more than additive among women. CONCLUSIONS: Our results in men showed an excess risk of lung cancer and its subtypes at low cumulative exposure levels, with a steeper exposure-response slope in this exposure range than at higher, previously studied levels. (See video abstract at, http://links.lww.com/EDE/B161.).
- MeSH
- Asbestos * MeSH
- Adult MeSH
- Smoking epidemiology MeSH
- Middle Aged MeSH
- Humans MeSH
- Logistic Models MeSH
- Small Cell Lung Carcinoma epidemiology MeSH
- Lung Neoplasms epidemiology MeSH
- Odds Ratio MeSH
- Occupational Exposure statistics & numerical data MeSH
- Aged MeSH
- Carcinoma, Squamous Cell epidemiology MeSH
- Case-Control Studies MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Europe epidemiology MeSH
- Canada epidemiology MeSH
Developments in managing CF continue to drive dramatic improvements in survival. As newborn screening rolls-out across Europe, CF centres are increasingly caring for cohorts of patients who have minimal lung disease on diagnosis. With the introduction of mutation-specific therapies and the prospect of truly personalised medicine, patients have the potential to enjoy good quality of life in adulthood with ever-increasing life expectancy. The landmark Standards of Care published in 2005 set out what high quality CF care is and how it can be delivered throughout Europe. This underwent a fundamental re-write in 2014, resulting in three documents; center framework, quality management and best practice guidelines. This document is a revision of the latter, updating standards for best practice in key aspects of CF care, in the context of a fast-moving and dynamic field. In continuing to give a broad overview of the standards expected for newborn screening, diagnosis, preventative treatment of lung disease, nutrition, complications, transplant/end of life care and psychological support, this consensus on best practice is expected to prove useful to clinical teams both in countries where CF care is developing and those with established CF centres. The document is an ECFS product and endorsed by the CF Network in ERN LUNG and CF Europe.
- MeSH
- Cystic Fibrosis complications diagnosis therapy MeSH
- Child MeSH
- Adult MeSH
- Infant MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Infant, Newborn MeSH
- Neonatal Screening MeSH
- Terminal Care MeSH
- Child, Preschool MeSH
- Practice Guidelines as Topic MeSH
- Social Support MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Infant MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Infant, Newborn MeSH
- Child, Preschool MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Geographicals
- Europe MeSH