Predictors and Prevalence of Nodal Disease in Salvage Oropharyngectomy.

BACKGROUND: Patients with recurrent oropharyngeal cancer often require extensive salvage surgery. For patients with clinically N0 necks, the indication for concurrent neck dissection remains unclear. This study aimed to determine predictors, prevalence, and distribution of nodal disease in patients treated with salvage oropharyngectomy. METHODS: In a case series with data collection at a single tertiary academic National Cancer Institute (NCI)-designated comprehensive cancer center, this study analyzed patients treated with prior radiation or chemoradiation who had persistent, recurrent, or second primary squamous cell carcinoma of the oropharynx requiring oropharyngeal resection between 1998 and 2017 (n = 95). Clinical and oncologic characteristics and treatment outcomes were collected, and statistical analyses were performed. RESULTS: The overall rate of nodal positivity was 21% (24/95), and the rate of occult nodal disease was 6% (4/65). Ipsilateral and contralateral level 2 were the most common areas harboring positive nodes. Bivariate analysis showed female sex (p = 0.01), initial overall stage (p = 0.02), and N status (p = 0.03), as well as recurrent overall and T stage (p = 0.05) to be predictors of nodal disease. In the multivariate analysis, recurrent T stage continued to be significantly predictive of pathologic nodal disease. Both computed tomography (CT) and positron emission tomography-CT were moderately accurate in predicting nodal disease in the salvage setting (area under the curve, 0.79 and 0.80, respectively). CONCLUSION: Occult nodal disease is observed in few patients undergoing salvage oropharyngeal resection. This study identified factors predictive of nodal disease in patients undergoing salvage oropharyngectomy and appropriate diagnostic tests in this setting.

Prevalence and distribution of sensitization to foods in the European Community Respiratory Health Survey: a EuroPrevall analysis.

BACKGROUND: Reports of adverse reactions to foods are increasing, but there is limited information on the comparative prevalence of sensitization to food allergens using standardized methods. METHODS: Sera from the 'random sample' of young adults seen during the second phase of the European Community Respiratory Health Survey were analysed for IgE against 24 foods using ImmunoCAP. Sera were tested on five food mixes, and subsequently on individual foods in each positive mix. RESULTS: Sera from 4522 individuals living in 13 countries were tested for at least one food allergen mix. Prevalence of sensitization to any of the 24 food allergens ranged from 24.6% in Portland (USA) to 7.7% in Reykjavik (Iceland). With few exceptions, the relative prevalence of sensitization to different foods was similar in all countries. Sensitization rates to egg, fish and milk were each less than 1%, and the most common sensitizations are not represented in current commercial mixes. The prevalence of sensitization to foods was not related to that of sensitization to aeroallergens but was related to the geometric mean total IgE for the country. CONCLUSIONS: Sensitization to foods is common but highly variable. The relative prevalence of sensitization to different foods is more consistent than would be expected by chance, suggesting that quantity of consumption of specific foods does not determine prevalence. The aetiology of food sensitization is only partly similar to that for aeroallergens but is related to local levels of total IgE. This may provide an important clue to the origins of food sensitization.

Relationship between oxidative stress-related biomarkers and antioxidant status with asthma and atopy in young adults: a population-based study.

BACKGROUND AND AIM: Enhanced oxidative stress has been described in adults who suffer from symptoms of asthma and poor lung function. This study assessed the relation between markers of oxidative stress and antioxidant status and lung function, symptoms of asthma, atopy and bronchial hyperresponsiveness (BHR) in young adults. METHODS: A sub-sample of 589 individuals aged 22-28 years, selected from a total of 1232 included in a survey assessing early and current risk factors for chronic diseases, participated in the study. Participants were from an agricultural area of Chile, responded to a Spanish version of the European Community Respiratory Health Survey questionnaire, were skin tested to eight allergens, and challenged with methacholine to assess BHR. Five hundred and eighty-five individuals had measures of plasma biomarkers ferric reducing ability of plasma, uric acid, protein carbonyls and 564 had 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha)) assessed. RESULTS: All participants had detectable plasma 8-iso-PGF(2alpha) and carbonyl levels. There was no indication for an association between markers of antioxidant status or oxidative stress with any of the outcomes studied. CONCLUSION: The levels of oxidative stress-related biomarkers and antioxidant status in plasma may not be related to asthma in the general population in the absence of more severe symptoms or exacerbations.

Age-aware constitutive materials model for a 3D printed polymeric foam.

Traditional open or closed-cell stochastic elastomeric foams have wide-ranging applications in numerous industries: from thermal insulation, shock absorbing/gap-filling support cushions, packaging, to light-weight structural and positional components. Recent developments in 3D printing technologies by direct ink-write have opened the possibility of replacing stochastic foam parts by more controlled printed micro-structures with superior stress-distribution and longer functional life. For successful deployment as mechanical support or structural components, it is crucial to characterize the response of such printed materials to long-term external loads in terms of stress-strain behavior evolution and in terms of irreversible structural and load-bearing capacity changes over time. To this end, here we report a thermal-age-aware constitutive model for a 3D printed close-packed foam structure under compression. The model is based on the Ogden hyperfoam strain-energy functional within the framework of Tobolsky two-network scheme. It accurately describes experimentally measured stress-strain response, compression set, and load retention for various aging times and temperatures. Through the technique of time-temperature-superposition the model enables the prediction of long-term changes along with the quantification of uncertainty stemming from sample-to-sample variation and measurement noise. All aging parameters appear to possess the same Arrhenius activation barrier, which suggests a single dominant aging mechanism at the molecular/network level.

Optimum expression of adult lung function based on all-cause mortality: results from the Reykjavik study.

A variety of reference curves are used to derive predicted values for adult lung function, even within ethnically similar populations. Alternatives to percentage predicted value are sometimes used to allow for height in research. Strength of association with total mortality can be used to choose the optimal expression, between forced expiratory volume in 1s (FEV(1)) divided by height(2), FEV(1)/height(3), FEV(1)% predicted and difference from predicted. Data from the Reykjavik Study cohort, 1976-2002, included 5544 men and 8062 women randomly selected from the population. Total mortality was analysed by Cox proportional hazards regression in relation to each height-adjusted measure, allowing for age group, period of recruitment and body mass index, and smoking before or at baseline. FEV(1)/height(2) and FEV(1)/height(3) had stronger associations with mortality than FEV(1)% predicted and difference from predicted in men and in women. There were similar findings for forced vital capacity (FVC) in non-smokers and in women. FEV(1)/height(2) was slightly better predictive than FEV(1)/height(3) in men, but distributions of FEV(1)/height(3) in men and women were closer than those of FEV(1)/height(2). Clinical practise and epidemiological research would benefit from agreement on how to adjust lung function for height. Replication of these analyses in other cohort studies would inform the choice between FEV(1)/height(2) and FEV(1)/height(3).

Developing a strategy to define the effects of insulin-like growth factor-1 on gene expression profile in cardiomyocytes.

Insulin-like growth factor (IGF)-1 activates intracellular signaling pathways and regulates myocardial structure and function. This study used DNA microarray to define the effects of IGF-1 on gene expression in cardiomyocytes. Despite DNA microarray becoming a popular tool for profiling gene expression, the specificity of DNA microarray results is rarely addressed. Our data showed that the specificity of a DNA microarray study can be increased by repetitive experiments and by excluding minimally expressed genes. In this study, the false-positive rates were reduced to <0.2%. Future DNA microarray studies should incorporate a proper strategy to minimize false-positive results. IGF-1 modulates the expression of genes in 17 functional categories, but most genes clustered around the regulation of intracellular signaling, cell cycle, transcription/translation, cellular respiration and mitochondrial function, cell survival, ion channels and calcium signaling, and humoral factors. To further explore whether extracellular signal-regulated kinase (ERK) and phosphatidylinositol (PI) 3 kinase specifically regulate different sets of genes, the effects of IGF-1 were inhibited with PD98059 or LY294002. The results showed that the majority of genes regulated by IGF-1 required activation of both ERK and PI 3 kinase. Thus, PI 3 kinase and ERK coordinately mediate the transcriptional regulatory effects of IGF-1 in cardiac muscle cells. These findings provide novel insight into how IGF-1 signaling modulates the programming of cardiac muscle gene expression.

Definitions of childhood obesity: current practice.

OBJECTIVE: To review current practice in the definition of childhood obesity based on body mass index (BMI), in order to understand why the recommendations of the International Task Force on Obesity (IOTF) have not been fully adopted. DESIGN: Literature search using MEDLINE to identify papers on childhood obesity published in the first 4 months of 2005, and a cited reference search on the recommendations of the IOTF. RESULTS: Citations of the IOTF definition have increased since publication, but less than half of papers on childhood obesity published in the period used the definition. Most used the 95th centile of a national distribution to define obesity. CONCLUSIONS: Reasons for using centiles of a national distribution included the need for z-scores or centiles to define underweight or extreme obesity, not available in conjunction with the IOTF definition, inclusion of children under 2 years, and concerns about over- or underestimation of the prevalence of obesity. None of these preclude use of the principle underlying the IOTF definition, that of continuity with the adult definition of BMI of 30 kg/m2 or more. Adoption of either the IOTF definition or corresponding centiles of a national distribution would enable comparisons of prevalence between countries and over time.

3D printed cellular solid outperforms traditional stochastic foam in long-term mechanical response.

3D printing of polymeric foams by direct-ink-write is a recent technological breakthrough that enables the creation of versatile compressible solids with programmable microstructure, customizable shapes, and tunable mechanical response including negative elastic modulus. However, in many applications the success of these 3D printed materials as a viable replacement for traditional stochastic foams critically depends on their mechanical performance and micro-architectural stability while deployed under long-term mechanical strain. To predict the long-term performance of the two types of foams we employed multi-year-long accelerated aging studies under compressive strain followed by a time-temperature-superposition analysis using a minimum-arc-length-based algorithm. The resulting master curves predict superior long-term performance of the 3D printed foam in terms of two different metrics, i.e., compression set and load retention. To gain deeper understanding, we imaged the microstructure of both foams using X-ray computed tomography, and performed finite-element analysis of the mechanical response within these microstructures. This indicates a wider stress variation in the stochastic foam with points of more extreme local stress as compared to the 3D printed material, which might explain the latter's improved long-term stability and mechanical performance.

Intraclass correlation coefficient and outcome prevalence are associated in clustered binary data.

BACKGROUND AND OBJECTIVE: To describe the association between values for a proportion and the intraclass correlation coefficient (ICC). METHODS: Analysis of data obtained from the General Practice Research Database (GPRD) for variation between United Kingdom general practices and results from a Health Technology Assessment (HTA) review for a range of outcomes in community and health services settings. RESULTS: There were 188 ICCs from the GPRD, the median prevalence was 13.1% (interquartile range IQR 3.5 to 28.4%) and median ICC 0.051 (IQR 0.011 to 0.094). There were 136 ICCs from the HTA review, with median prevalence 6.5% (IQR 0.4 to 20.7%) and median ICC 0.006 (IQR 0.0003 to 0.036). There was a linear association of log ICC with log prevalence in both datasets (GPRD, regression coefficient 0.61, 95% confidence interval 0.53 to 0.69, P < 0.001; HTA, 0.91, 0.81 to 1.01, P < 0.001). When the prevalence was 1% the predicted ICC was 0.008 from the GPRD or 0.002 from the HTA, but when the prevalence was 40% the predicted ICC was 0.075 (GPRD) or 0.046 (HTA). CONCLUSION: The prevalence of an outcome may be used to make an informed assumption about the magnitude of the intraclass correlation coefficient.

Is methicillin-resistant Staphylococcus aureus more virulent than methicillin-susceptible S. aureus? A comparative cohort study of British patients with nosocomial infection and bacteremia.

Staphylococcus aureus is the most common cause of hospital-acquired bacteremia. From 1995 through 2000, data on age, sex, patient specialty at time of first bacteremia, primary and secondary sites of infection, delay in initiating antimicrobial therapy, and patient outcome were prospectively recorded for 815 patients with nosocomial S. aureus bacteremia. The proportion of patients whose death was attributable to methicillin-resistant S. aureus (MRSA) was significantly higher than that for methicillin-susceptible S. aureus (MSSA) (11.8% vs. 5.1%; odds ratio [OR], 2.49; 95% confidence interval [CI], 1.46-4.24; P<.001). After adjustment for host variables, the OR decreased to 1.72 (95% CI, 0.92-3.20; P=.09). There was no significant difference between rates of disseminated infection (7.1% vs. 6.2% for MRSA-infected patients and MSSA-infected patients, respectively; P=.63), though the rate of death due to disseminated infection was significantly higher than death due to uncomplicated infection (37% vs. 10% for MRSA-infected patients [P<.001] and 37% vs. 3% for MSSA-infected patients [P<.001]). There was a strong statistical trend toward death due to nosocomial MRSA infection and bacteremia, compared with MSSA.

Analysis of human lymphocyte transformation responses to graded doses of T cell mitogens by curve fitting.

The between-group comparison of complete lymphocyte transformation dose-response curves is complex. We have therefore derived a mathematical model of the dose-response characteristics of human mononuclear cells to stimulation by concanavalin A (ConA) and purified phytohaemagglutinin (PHA), in order to simplify such analyses. This model describes dose-response curves in terms of the magnitude of the peak response, the dose of mitogen that elicits the peak and an estimate of the range of mitogen doses which induce a response. Responses to ConA were described by the model more precisely than those to PHA. Furthermore, use of the model revealed differences between anorexia nervosa patients and healthy subjects in terms of the dose of mitogen necessary to elicit a peak response and the range of mitogen concentrations producing a response. It is proposed that this form of mathematical treatment may be of use for the comparison of lymphocyte transformation dose-response curves and for the valid rejection of suspect results.

Developing a new questionnaire for measuring the prevalence and distribution of asthma.

Over the last few years the International Union Against Tuberculosis (IUAT) has been developing a new questionnaire for measuring the prevalence and distribution of asthma. The methods that are being used to establish the validity of the questionnaire are described, along with some preliminary results. These results are used to illustrate a number of problems. Current work concerning the further development and testing of the questionnaire is described.

Monitoring the growth of children: conclusions from a long-term study.

BACKGROUND: The National Study of Health and Growth (NSHG) was set up in 1972 to monitor the growth of primary school children. Areas were selected in England and Scotland by stratified random sampling. Schools within these areas were visited annually until 1982, biennially thereafter, resulting in a mixed longitudinal design. The reasons for the original design and the study as it has operated are reviewed, with advantages and disadvantages compared to the monitoring system now to be implemented by the Department of Health. METHODS: Description of the statistical and interpretive problems of monitoring rates of growth and a comparison of the response rates achieved in the two types of monitoring. RESULTS: Although the design of the NSHG was selected in order to monitor rates of growth this presents statistical problems. The usable information is contained in trends in attained height rather than in rates of growth. This study has achieved an average response rate of over 95%; less than 78% can be expected from the proposed survey of households. CONCLUSIONS: The small loss of efficiency of the mixed longitudinal design compared with repeated cross-sectional studies is more than compensated for by its high response rate and the comparability of data over time, neither of which can be guaranteed by the proposed survey.

On measuring repeatability of data from self-administered questionnaires.

It is usually necessary to estimate repeatability of a self-administered questionnaire from responses by subjects on just two occasions. It is shown that it is not possible to estimate false positive and false negative classification rates separately, but that an average correct classification can be calculated. This is recommended as the appropriate absolute measure of repeatability, whereas the kappa statistic, which can be interpreted as the ratio of between subject to total variation, is a measure of repeatability relative to prevalence of responses. Both measures should be calculated to give complete information on repeatability, analogous to absolute and relative measures used for continuous variables.

Exposure to cigarette smoking and children's growth.

An analysis of data from 5903 children from a study of primary schools in England and Scotland in 1982 showed that the number of cigarettes smoked by the parents at home was significantly associated with the attained height of their children. This relation was statistically significant after allowing for parents' height, child's birthweight, mother's smoking during pregnancy, overcrowding and number of older siblings. Number of cigarettes smoked at home was more strongly related to height than number of cigarettes smoked by the mother during pregnancy. The results suggest that passive smoking may have an effect on the height of a child independent of genetic factors, the social environment and mother's smoking in pregnancy. Whether this is a direct effect of parents' smoking on the child's growth remains unclear.

The relation of the height of primary school children to population density.

The relation of the height of primary school children to population density, as measured at the 1971 census, was investigated for children in 21 study areas in England, using data from the 1972 survey of the National Study of Health and Growth. Shorter stature was found with increasing population density, and this relation remained after allowing for child's birthweight, mother's height, father's height, social class, number of siblings, and additionally a measure of home overcrowding. The results are in contrast to those found elsewhere, and are unlikely to indicate a cause-and-effect relationship between population density and height. The findings cannot be explained either by known differences between urban and rural areas in social characteristics or by plausible hypotheses of genetic heterogeneity.

Variation in physical fitness between ethnic groups in nine year olds.

BACKGROUND: There is little information on cardio-respiratory fitness of children, especially in ethnic minorities in Britain. In this study we assess the associations of social factors, ethnicity, parental health related factors, child's anthropometry, blood pressure and cholesterol measurements with cardio-respiratory fitness. METHODS: Power output against load at 85% of the maximum heart rate (PWC85%), was measured, using a cycle-ergometer test, in children aged 8-9 years in 22 randomly selected areas in England, 14 in Scotland and in 20 inner city areas in England. The subjects were 317 boys and 310 girls from the English sample, 152 boys and 140 girls from the Scottish sample and 242 boys and 261 girls from the inner city sample. RESULTS: Short stature (P < 0.001), fatness (P < 0.001), and Indian subcontinent origin (OR = 0.34, 95% CI: 0.16, 0.68 in boys and OR = 0.22, 95% CI: 0.12, 0.40 in girls) were associated with inability to finish the test. In those who finished the test PWC85% was greater in taller children and in those with lower skinfold values (P < 0.001, except height in boys P = 0.017). The PWC85% in those originating in the Indian continent was lower (-0.17 watt/kg, 95% CI :-0.32, -0.01 in boys and -0.29, 95% CI: -0.43, -0.14 in girls) than in white children. CONCLUSIONS: Shorter and obese children have poorer physical fitness than other children. Physical fitness is lower in children originating in the Indian subcontinent than other British children. This seems to be unrelated to socioeconomic disadvantage. Physical inactivity and lack of cycling skills may explain our findings.

Overweight, obesity and skinfold thicknesses of children of African or Indian descent in Trinidad and Tobago.

BACKGROUND: To evaluate distribution of body mass index (BMI) and subcutaneous fat in children of African or Indian subcontinent descent living in Trinidad and Tobago. METHODS: A cross-sectional survey was carried out in a nationally representative sample of 66 government schools. Measurements were made of children's heights, weights, triceps and subscapular skinfold thicknesses. Data were analysed by sex and ethnic group and comparison was made with international standards for overweight and obesity and with British (1990) reference curves for BMI. RESULTS: Data were analysed for 5688/6731 (85%) eligible children including 1934 Afro-Trinidadian, 1689 Indo-Trinidadian, and 1794 of mixed ethnicity. Afro-Trinidadian and mixed children were taller, but Indo-Trinidadian children were shorter than reference. Values for BMI were lower than reference: mean standard deviation score (SDS), (95% confidence interval) Afro-Trinidadian -0.34 (-0.39 to -0.28), Indo-Trinidadian -1.32 (-1.39 to -1.25), mixed -0.67 (-0.74 to -0.61). Overall 486 (8.5%, 7.8 to 9.3%) of children were overweight and 138 (2.4%, 2.0 to 2.9%) were obese. Triceps skinfold thickness values were lower than reference (-0.45, -0.48 to -0.42 SDS) but subscapular skinfold thicknesses were higher (0.45, 0.43 to 0.47 SDS). Higher BMI were associated with higher BMI in the child's parents, higher reported birthweight, older age of the child's mother, smaller family size, and with higher maternal educational attainment. CONCLUSIONS: Overweight was prevalent and distribution of subcutaneous fat was central. Work is needed to determine whether these findings are associated with adult patterns of fat distribution and metabolic abnormalities.

What symptoms predict the bronchial response to histamine? Evaluation in a community survey of the bronchial symptoms questionnaire (1984) of the International Union Against Tuberculosis and Lung Disease.

A questionnaire developed by the International Union against Tuberculosis and Lung Disease (IUATLD) to assess bronchial symptoms has been tested for its ability to predict the bronchial response to histamine in adults aged 18-64 years living in two areas of southern England. A number of questions were found to be independently associated with increased reactivity in the first randomly selected half of the subjects. These symptoms included wheeze, waking at night with shortness of breath, tightness in the chest or shortness of breath when exposed to animals, dust or feathers and the non-specific symptom of persistent problems with breathing. A predictive score based on these symptoms was more sensitive and only slightly less specific than the question on wheeze alone in predicting the response to histamine in the second half of the subjects. Questions about asthma though more specific were considerably less sensitive than either. Symptoms did not differentiate between reactivity associated with positive skin tests and that associated with smoking.

The relation between respiratory illness in primary schoolchildren and the use of gas for cooking--II. Factors affecting nitrogen dioxide levels in the home.

The study was designed to determine whether there was an association between indoor levels of nitrogen dioxide (NO2) and respiratory illness and lung function in schoolchildren. NO2 was measured for one week in the winter outside and inside the homes of children aged 6-7 years living and attending primary schools in a defined 4 square km area in Middlesbrough, Cleveland, UK. Outdoor levels of NO2 measured at 75 points within the area ranged from 14-24 ppb weekly average. Measurements were also made in 428 kitchens with gas cookers, range 5-317 ppb, mean 112.2 ppb, and in 87 kitchens with electric cookers, range 6-188 ppb, mean 18.0 ppb. In a random subsample of homes the range of NO2 levels in 107 children's bedrooms in homes where gas was used for cooking was 4-169 ppb, mean 30.5 ppb, in 18 bedrooms in electric cooking homes the range was 3-37 ppb, mean 13.9 ppb. NO2 levels in the gas cooking kitchens were positively related to the presence of pilot lights, use of gas fires for main heating, number of regular smokers, and the number of people in the home. Information from 29 homes with the highest kitchen NO2 levels paired with 29 low NO2 gas cooking homes showed that the daily number of meals eaten and the frequency with which the cooker was used for heating and drying clothes were significantly greater in the high NO2 homes.