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.

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.

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.

Mullins effect in a filled elastomer under uniaxial tension.

Modulus softening and permanent set in filled polymeric materials due to cyclic loading and unloading, commonly known as the Mullins effect, can have a significant impact on their use as support cushions. A quantitative analysis of such behavior is essential to ensure the effectiveness of such materials in long-term deployment. In this work we combine existing ideas of filler-induced modulus enhancement, strain amplification, and irreversible deformation within a simple non-Gaussian constitutive model to quantitatively interpret recent measurements on a relevant PDMS-based elastomeric cushion. We find that the experimental stress-strain data is consistent with the picture that during stretching (loading) two effects take place simultaneously: (1) the physical constraints (entanglements) initially present in the polymer network get disentangled, thus leading to a gradual decrease in the effective cross-link density, and (2) the effective filler volume fraction gradually decreases with increasing strain due to the irreversible pulling out of an initially occluded volume of the soft polymer domain.

Radiation-induced mechanical property changes in filled rubber.

In a recent paper we exposed a filled elastomer to controlled radiation dosages and explored changes in its cross-link density and molecular weight distribution between network junctions [A. Maiti et al., Phys. Rev. E 83, 031802 (2011)]. Here we report mechanical response measurements when the material is exposed to radiation while being under finite nonzero strain. We observe interesting hysteretic behavior and material softening representative of the Mullins effect, and materials hardening due to radiation. The net magnitude of the elastic modulus depends upon the radiation dosage, strain level, and strain-cycling history of the material. Using the framework of Tobolsky's two-stage independent network theory we develop a model that can quantitatively interpret the observed elastic modulus and its radiation and strain dependence.

Controlled manipulation of elastomers with radiation: Insights from multiquantum nuclear-magnetic-resonance data and mechanical measurements.

Filled and cross-linked elastomeric rubbers are versatile network materials with a multitude of applications ranging from artificial organs and biomedical devices to cushions, coatings, adhesives, interconnects, and seismic-isolation, thermal, and electrical barriers. External factors such as mechanical stress, temperature fluctuations, or radiation are known to create chemical changes in such materials that can directly affect the molecular weight distribution (MWD) of the polymer between cross-links and alter the structural and mechanical properties. From a materials science point of view it is highly desirable to understand, affect, and manipulate such property changes in a controlled manner. Unfortunately, that has not yet been possible due to the lack of experimental characterization of such networks under controlled environments. In this work we expose a known rubber material to controlled dosages of γ radiation and utilize a newly developed multiquantum nuclear-magnetic-resonance technique to characterize the MWD as a function of radiation. We show that such data along with mechanical stress-strain measurements are amenable to accurate analysis by simple network models and yield important insights into radiation-induced molecular-level processes.

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.

Eczema, atopy and allergen exposure in adults: a population-based study.

BACKGROUND: There are few published studies on geographical variation in prevalence of eczema in adults or its association with recognised risk factors for allergic disease. OBJECTIVE: To describe the geographical variation in prevalence of eczema in adults, assess the associations with sociodemographic risk factors, serum-specific IgE and IgG, and exposure to allergen. METHODS: A community-based sample of 8206 adults aged 27-56 years, in 25 European centres and Portland, USA, provided questionnaire information on symptoms of eczema. Serum-specific IgE to house dust mite (HDM), cat, grass and Cladosporium, and IgG and IgG4 to HDM and cat were measured. Mattress levels of mite and cat allergen were assessed. RESULTS: Overall prevalence of eczema was 7.1% (range between countries of 2.2-17.6%). Eczema was associated with female gender [odds ratio (OR) 1.25; 95% confidence interval (CI) (1.01-1.55)], family history of atopic disease (OR 1.43; 95% CI 1.18-1.74), IgE sensitization to at least one allergen (OR 1.50; 95% CI 1.19-1.90), particularly Cladosporium (OR 3.65; 95% CI 1.81-7.37), and total IgE. Eczema was negatively associated with age and no clear associations were observed with sibship size, mattress mite and cat allergen levels or with cat and HDM-specific IgG or IgG4. CONCLUSIONS: There is geographical variation in the prevalence of eczema in adults both within and between countries. Although the disease is associated with IgE sensitization, in this study it was not related to mattress mite or cat allergen levels.

Geographical variation in the prevalence of positive skin tests to environmental aeroallergens in the European Community Respiratory Health Survey I.

BACKGROUND: Many studies have reported the prevalence of sensitization using skin prick tests. However, comparisons between studies and between regions are difficult because the number and the type of allergens tested vary widely. Using the European Community Health Respiratory Survey I data, the geographical variation of sensitization to environmental allergen as measured by skin tests was established. METHODS: Adults aged 20-44 years, living in 35 centres in 15 developed countries, underwent skin tests for allergy to nine common aeroallergens: Dermatophagoides pteronyssinus, timothy grass, cat, Cladosporium herbarium, Alternaria alternata, birch, Olea europea, common ragweed and Parietaria judaica. The age-sex standardized prevalence of sensitization was determined and centres with high (95% confidence interval above and excluding study median) and low prevalence (95% confidence interval below and excluding study median) of sensitization to each allergen and to any of the nine allergens were identified. RESULTS: There was substantial geographical variation in the prevalence of sensitization to each of the nine allergens tested and in the prevalence of sensitization to any allergen (lowest 17.1%, median 36.8% and highest 54.8%). Sensitization to D. pteronyssinus, grass pollen and cat were usually the most prevalent (median between centre 21.7%, 16.9% and 8.8%, respectively). Timothy grass sensitization was higher than that for any other pollen species. CONCLUSIONS: As expected, geographical variations of sensitization to environmental allergen were observed across centres. These findings were compatible for those observed with serum-specific IgE. Skin tests can be used to assess the geographical distribution of allergens in a multicentric epidemiological survey.

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).

Incidence of asthma and net change in symptoms in relation to changes in obesity.

The incidence of asthma has been reported to be associated with obesity. An alternative analysis, of net change in prevalence, does not require exclusion of those with asthma at baseline. Follow-up data were obtained from 9,552 participants in the European Community Respiratory Health Survey and the Swiss cohort Study on Air Pollution and Lung Disease in Adults. Incidence of asthma was analysed by proportional hazards regression, and net changes in symptoms and asthma status by generalised estimating equations, by obesity group. Incidence and net change in ever having had asthma were greater in females than in males, and in participants who remained obese compared with those who were never obese (hazard ratio 2.00, 95% confidence interval 1.25-3.20; excess net change 2.8%, 0.4-5.3% per 10 yrs). The effect of being obese on net change in diagnosed asthma was greater in females than in males, but for net change in wheeze without a cold it was greater in males. The present results are consistent with asthma being more frequently diagnosed in females, especially obese females. These findings may help to explain the reports of a stronger association between asthma and obesity in females than in males.

Sources of variation in forced expiratory volume in one second and forced vital capacity.

Published prediction equations for lung function differ considerably, but the components of population variation responsible for the differences are unknown. Data were analysed for 6,323 never-smoking adults who did not report wheeze or asthma, from 42 centres participating in the European Community Respiratory Health Survey. Means and components of variance were estimated for males and females aged 20-24 yrs, and the relationships with age and height were examined in those aged 25-44 yrs. Mean lung function for those aged 20-24 yrs differed between centres, but variation could not be wholly attributed to differences in population or equipment. The maximum difference in means by equipment type was 101 mL for FVC in males. Equipment differences were not statistically significant adjusted for country, but differences in mean forced expiratory volume in one second and forced vital capacity by country, adjusted for instrument, were statistically significant in males. Differences between centres in relation to age and height had less influence on predicted values. In conclusion, there are unexplained differences in lung function between ethnically similar nonsmoking symptom-free populations. Neither national reference curves nor those based on the same ethnic group can be guaranteed to give accurate norms of lung health.

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.

Changes in active and passive smoking in the European Community Respiratory Health Survey.

The aim of the present investigation was to study changes and determinants for changes in active and passive smoking. The present study included 9,053 adults from 14 countries that participated in the European Community Respiratory Health Survey II. The mean follow-up period was 8.8 yrs. Change in the prevalence of active and passive smoking was expressed as absolute net change (95% confidence interval) standardised to a 10-yr period. Determinants of change were analysed and the results expressed as adjusted hazard risk ratio (HRR) or odds ratio (OR). The prevalence of active smoking declined by 5.9% (5.1-6.8) and exposure to passive smoking in nonsmokers declined by 18.4% (16.8-20.0). Subjects with a lower educational level (HRR: 0.73 (0.54-0.98) and subjects living with a smoker (HRR: 0.45 (0.34-0.59)) or with workplace smoking (HRR: 0.69 (0.50-0.95)) were less likely to quit. Low socio-economic groups were more likely to become exposed (OR: 2.21 (1.61-3.03)) and less likely to cease being exposed to passive smoking (OR: 0.48 (0.37-0.61)). In conclusion, the quitting rate was lower and the risk of exposure to passive smoking higher among subjects with lower socio-economic status. Exposure to other peoples smoking decreased quitting rates and increased the risk of starting to smoke.

Indoor nitrous acid and respiratory symptoms and lung function in adults.

BACKGROUND: Nitrogen dioxide (NO2) is an important pollutant of indoor and outdoor air, but epidemiological studies show inconsistent health effects. These inconsistencies may be due to failure to account for the health effects of nitrous acid (HONO) which is generated directly from gas combustion and indirectly from NO2. METHODS: Two hundred and seventy six adults provided information on respiratory symptoms and lung function and had home levels of NO2 and HONO measured as well as outdoor levels of NO2. The association of indoor HONO levels with symptoms and lung function was examined. RESULTS: The median indoor HONO level was 3.10 ppb (IQR 2.05-5.09), with higher levels in homes with gas hobs, gas ovens, and in those measured during the winter months. Non-significant increases in respiratory symptoms were observed in those living in homes with higher HONO levels. An increase of 1 ppb in indoor HONO was associated with a decrease in forced expiratory volume in 1 second (FEV1) percentage predicted (-0.96%; 95% CI -0.09 to -1.82) and a decrease in percentage FEV1/forced vital capacity (FVC) (-0.45%; 95% CI -0.06 to -0.83) after adjustment for relevant confounders. Measures of indoor NO2 were correlated with HONO (r = 0.77), but no significant association of indoor NO2 with symptoms or lung function was observed. After adjustment for NO2 measures, the association of HONO with low lung function persisted. CONCLUSION: Indoor HONO levels are associated with decrements in lung function and possibly with more respiratory symptoms. Inconsistencies between studies examining health effects of NO2 and use of gas appliances may be related to failure to account for this association.

Overweight and obesity trends from 1974 to 2003 in English children: what is the role of socioeconomic factors?

AIMS: To examine the childhood overweight and obesity prevalence trends between 1974 and 2003 and to assess whether these trends relate to parental social class and household income. METHODS: A school based and a general population health survey: the National Study of Health and Growth in 1974, 1984, and 1994, and the Health Survey for England, yearly from 1996 to 2003. Participants were 14,587 white boys and 14,014 white girls aged 5-10 years. Overweight and obesity prevalence were calculated using UK specific as well as international body mass index (kg/m2) cut-offs. Socioeconomic status was measured using the Registrar General's social class; household income (1997 onwards only) was adjusted for household size. RESULTS: The prevalence of obesity (UK specific definition) in boys increased from 1.2% in 1984 to 3.4% in 1996-97 and 6.0% in 2002-03. In girls, obesity increased from 1.8% in 1984 to 4.5% in 1996-97 and 6.6% in 2002-03. Obesity prevalence has been increasing at accelerating rates in the more recent years. Children from manual social classes had marginally higher odds (OR 1.14, 95% CI 0.98 to 1.33) and children from higher income households had lower odds (OR 0.74, 95% CI 0.61 to 0.89) to be obese than their peers from non-manual class, and lower income households, respectively. CONCLUSION: Childhood obesity is increasing rapidly into the 2000s in England and these increases are more marked among children from lower socioeconomic strata. There is an urgent need for action to prevent further increase in obesity among children.

Reproducibility of non-specific bronchial challenge in adults: implications for design, analysis and interpretation of clinical and epidemiological studies.

BACKGROUND: Poor reproducibility of an outcome measure reduces power and, in an independent variable, biases results. The intraclass correlation coefficient measures loss of power and degree of bias. Information is lacking on the intraclass correlation coefficient for bronchial responsiveness and factors affecting reproducibility. METHODS: Papers containing information on reproducibility of bronchial responsiveness were identified using a Medline search and citations. Within and between person components of variance of PD20 or PC20 were expressed in doubling dose or concentration units, and the intraclass correlation coefficient calculated when not reported. RESULTS: Results were extracted from 32 papers. Intraclass correlation coefficients were over 0.9 in short term studies of highly selected asthmatic patients, but larger and most long term studies had lower intraclass correlation coefficients, less than 0.5 in some cases, due to greater within person or lower between person variation. Reproducibility of dose or concentration-response slope was generally higher, but still less than that of forced expiratory volume in 1 second. CONCLUSIONS: Information is available to calculate sample size for studies with bronchial responsiveness as the outcome, but results when bronchial responsiveness is an explanatory variable may be misleading.