Risk factors for head and neck cancer in young adults: a pooled analysis in the INHANCE consortium.

BACKGROUND: Increasing incidence of head and neck cancer (HNC) in young adults has been reported. We aimed to compare the role of major risk factors and family history of cancer in HNC in young adults and older patients. METHODS: We pooled data from 25 case-control studies and conducted separate analyses for adults ≤45 years old ('young adults', 2010 cases and 4042 controls) and >45 years old ('older adults', 17 700 cases and 22 704 controls). Using logistic regression with studies treated as random effects, we estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The young group of cases had a higher proportion of oral tongue cancer (16.0% in women; 11.0% in men) and unspecified oral cavity / oropharynx cancer (16.2%; 11.1%) and a lower proportion of larynx cancer (12.1%; 16.6%) than older adult cases. The proportions of never smokers or never drinkers among female cases were higher than among male cases in both age groups. Positive associations with HNC and duration or pack-years of smoking and drinking were similar across age groups. However, the attributable fractions (AFs) for smoking and drinking were lower in young when compared with older adults (AFs for smoking in young women, older women, young men and older men, respectively, = 19.9% (95% CI = 9.8%, 27.9%), 48.9% (46.6%, 50.8%), 46.2% (38.5%, 52.5%), 64.3% (62.2%, 66.4%); AFs for drinking = 5.3% (-11.2%, 18.0%), 20.0% (14.5%, 25.0%), 21.5% (5.0%, 34.9%) and 50.4% (46.1%, 54.3%). A family history of early-onset cancer was associated with HNC risk in the young [OR = 2.27 (95% CI = 1.26, 4.10)], but not in the older adults [OR = 1.10 (0.91, 1.31)]. The attributable fraction for family history of early-onset cancer was 23.2% (8.60% to 31.4%) in young compared with 2.20% (-2.41%, 5.80%) in older adults. CONCLUSIONS: Differences in HNC aetiology according to age group may exist. The lower AF of cigarette smoking and alcohol drinking in young adults may be due to the reduced length of exposure due to the lower age. Other characteristics, such as those that are inherited, may play a more important role in HNC in young adults compared with older adults.

Natural vitamin C intake and the risk of head and neck cancer : a pooled analysis in the International Head and Neck Cancer Epidemiology Consortium

Evidence of associations between single nutrients and head and neck cancer (HNC) is still more limited and less consistent than that for fruit and vegetables. However, clarification of the protective mechanisms of fruit and vegetables is important to our understanding of HNC etiology. We investigated the association between vitamin C intake from natural sources and cancer of the oral cavity/pharynx and larynx using individual-level pooled data from ten case-control studies (5,959 cases and 12,248 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium. After harmonization of study-specific exposure information via the residual method, adjusted odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using unconditional multiple logistic regression models on quintile categories of 'non-alcohol energy-adjusted' vitamin C intake. In the presence of heterogeneity of the estimated ORs among studies, we derived those estimates from generalized linear mixed models. Higher intakes of vitamin C were inversely related to oral and pharyngeal (OR = 0.54, 95% CI: 0.45-0.65, for the fifth quintile category versus the first one, p for trend<0.001) and laryngeal cancers (OR = 0.52, 95% CI: 0.40-0.68, p for trend = 0.006), although in the presence of heterogeneity among studies for both sites. Inverse associations were consistently observed for the anatomical subsites of oral and pharyngeal cancer, and across strata of age, sex, education, body mass index, tobacco, and alcohol, for both cancer sites. The inverse association of vitamin C intake from foods with HNC may reflect a protective effect on these cancers; however, we cannot rule out other explanations.

Vitamin E intake from natural sources and head and neck cancer risk : a pooled analysis in the International Head and Neck Cancer Epidemiology consortium.

BACKGROUND: Evidence for the possible effect of vitamin E on head and neck cancers (HNCs) is limited. METHODS: We used individual-level pooled data from 10 case-control studies (5959 cases and 12 248 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium to assess the association between vitamin E intake from natural sources and cancer of the oral cavity/pharynx and larynx. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression models applied to quintile categories of nonalcohol energy-adjusted vitamin E intake. RESULTS: Intake of vitamin E was inversely related to oral/pharyngeal cancer (OR for the fifth vs the first quintile category=0.59, 95% CI: 0.49-0.71; P for trend <0.001) and to laryngeal cancer (OR=0.67, 95% CI: 0.54-0.83, P for trend <0.001). There was, however, appreciable heterogeneity of the estimated effect across studies for oral/pharyngeal cancer. Inverse associations were generally observed for the anatomical subsites of oral and pharyngeal cancer and within covariate strata for both sites. CONCLUSION: Our findings suggest that greater vitamin E intake from foods may lower HNC risk, although we were not able to explain the heterogeneity observed across studies or rule out certain sources of bias.

An inertial sensor-based system for spatio-temporal analysis in classic cross-country skiing diagonal technique.

The present study proposes a method based on ski fixed inertial sensors to automatically compute spatio-temporal parameters (phase durations, cycle speed and cycle length) for the diagonal stride in classical cross-country skiing. The proposed system was validated against a marker-based motion capture system during indoor treadmill skiing. Skiing movement of 10 junior to world-cup athletes was measured for four different conditions. The accuracy (i.e. median error) and precision (i.e. interquartile range of error) of the system was below 6ms for cycle duration and ski thrust duration and below 35ms for pole push duration. Cycle speed precision (accuracy) was below 0.1m/s (0.005m/s) and cycle length precision (accuracy) was below 0.15m (0.005m). The system was sensitive to changes of conditions and was accurate enough to detect significant differences reported in previous studies. Since capture volume is not limited and setup is simple, the system would be well suited for outdoor measurements on snow.

Impact of early valve surgery on outcome of Staphylococcus aureus prosthetic valve infective endocarditis: analysis in the International Collaboration of Endocarditis-Prospective Cohort Study.

BACKGROUND: The impact of early valve surgery (EVS) on the outcome of Staphylococcus aureus (SA) prosthetic valve infective endocarditis (PVIE) is unresolved. The objective of this study was to evaluate the association between EVS, performed within the first 60 days of hospitalization, and outcome of SA PVIE within the International Collaboration on Endocarditis-Prospective Cohort Study. METHODS: Participants were enrolled between June 2000 and December 2006. Cox proportional hazards modeling that included surgery as a time-dependent covariate and propensity adjustment for likelihood to receive cardiac surgery was used to evaluate the impact of EVS and 1-year all-cause mortality on patients with definite left-sided S. aureus PVIE and no history of injection drug use. RESULTS: EVS was performed in 74 of the 168 (44.3%) patients. One-year mortality was significantly higher among patients with S. aureus PVIE than in patients with non-S. aureus PVIE (48.2% vs 32.9%; P = .003). Staphylococcus aureus PVIE patients who underwent EVS had a significantly lower 1-year mortality rate (33.8% vs 59.1%; P = .001). In multivariate, propensity-adjusted models, EVS was not associated with 1-year mortality (risk ratio, 0.67 [95% confidence interval, .39-1.15]; P = .15). CONCLUSIONS: In this prospective, multinational cohort of patients with S. aureus PVIE, EVS was not associated with reduced 1-year mortality. The decision to pursue EVS should be individualized for each patient, based upon infection-specific characteristics rather than solely upon the microbiology of the infection causing PVIE.

Mercury analysis in hair: comparability and quality assessment within the transnational COPHES/DEMOCOPHES project

Human biomonitoring (HBM) is an effective tool for assessing actual exposure to chemicals that takes into account all routes of intake. Although hair analysis is considered to be an optimal biomarker for assessing mercury exposure, the lack of harmonization as regards sampling and analytical procedures has often limited the comparison of data at national and international level. The European-funded projects COPHES and DEMOCOPHES developed and tested a harmonized European approach to Human Biomonitoring in response to the European Environment and Health Action Plan. Herein we describe the quality assurance program (QAP) for assessing mercury levels in hair samples from more than 1800 mother-child pairs recruited in 17 European countries. To ensure the comparability of the results, standard operating procedures (SOPs) for sampling and for mercury analysis were drafted and distributed to participating laboratories. Training sessions were organized for field workers and four external quality-assessment exercises (ICI/EQUAS), followed by the corresponding web conferences, were organized between March 2011 and February 2012. ICI/EQUAS used native hair samples at two mercury concentration ranges (0.20-0.71 and 0.80-1.63) per exercise. The results revealed relative standard deviations of 7.87-13.55% and 4.04-11.31% for the low and high mercury concentration ranges, respectively. A total of 16 out of 18 participating laboratories the QAP requirements and were allowed to analyze samples from the DEMOCOPHES pilot study. Web conferences after each ICI/EQUAS revealed this to be a new and effective tool for improving analytical performance and increasing capacity building. The procedure developed and tested in COPHES/DEMOCOPHES would be optimal for application on a global scale as regards implementation of the Minamata Convention on Mercury.

Effect of Smoking on Blood Pressure and Resting Heart Rate: A Mendelian Randomization Meta-Analysis in the CARTA Consortium.

BACKGROUND: Smoking is an important cardiovascular disease risk factor, but the mechanisms linking smoking to blood pressure are poorly understood. METHODS AND RESULTS: Data on 141 317 participants (62 666 never, 40 669 former, 37 982 current smokers) from 23 population-based studies were included in observational and Mendelian randomization meta-analyses of the associations of smoking status and smoking heaviness with systolic and diastolic blood pressure, hypertension, and resting heart rate. For the Mendelian randomization analyses, a genetic variant rs16969968/rs1051730 was used as a proxy for smoking heaviness in current smokers. In observational analyses, current as compared with never smoking was associated with lower systolic blood pressure and diastolic blood pressure and lower hypertension risk, but with higher resting heart rate. In observational analyses among current smokers, 1 cigarette/day higher level of smoking heaviness was associated with higher (0.21 bpm; 95% confidence interval 0.19; 0.24) resting heart rate and slightly higher diastolic blood pressure (0.05 mm Hg; 95% confidence interval 0.02; 0.08) and systolic blood pressure (0.08 mm Hg; 95% confidence interval 0.03; 0.13). However, in Mendelian randomization analyses among current smokers, although each smoking increasing allele of rs16969968/rs1051730 was associated with higher resting heart rate (0.36 bpm/allele; 95% confidence interval 0.18; 0.54), there was no strong association with diastolic blood pressure, systolic blood pressure, or hypertension. This would suggest a 7 bpm higher heart rate in those who smoke 20 cigarettes/day. CONCLUSIONS: This Mendelian randomization meta-analysis supports a causal association of smoking heaviness with higher level of resting heart rate, but not with blood pressure. These findings suggest that part of the cardiovascular risk of smoking may operate through increasing resting heart rate.

Typology of "Fatigue" by Heart Rate Variability Analysis in Elite Nordic-skiers.

This study investigated changes in heart rate variability (HRV) in elite Nordic-skiers to characterize different types of "fatigue" in 27 men and 30 women surveyed from 2004 to 2008. R-R intervals were recorded at rest during 8 min supine (SU) followed by 7 min standing (ST). HRV parameters analysed were powers of low (LF), high (HF) frequencies, (LF+HF) (ms(2)) and heart rate (HR, bpm). In the 1 063 HRV tests performed, 172 corresponded to a "fatigue" state and the first were considered for analysis. 4 types of "fatigue" (F) were identified: 1. F(HF(-)LF(-))SU_ST for 42 tests: decrease in LFSU (- 46%), HFSU (- 70%), LFST (- 43%), HFST (- 53%) and increase in HRSU (+ 15%), HRST (+ 14%). 2. F(LF(+) SULF(-) ST) for 8 tests: increase in LFSU (+ 190%) decrease in LFST (- 84%) and increase in HRST (+ 21%). 3. F(HF(-) SUHF(+) ST) for 6 tests: decrease in HFSU (- 72%) and increase in HFST (+ 501%). 4. F(HF(+) SU) for only 1 test with an increase in HFSU (+ 2161%) and decrease in HRSU (- 15%). Supine and standing HRV patterns were independently modified by "fatigue". 4 "fatigue"-shifted HRV patterns were statistically sorted according to differently paired changes in the 2 postures. This characterization might be useful for further understanding autonomic rearrangements in different "fatigue" conditions.

Timing History: The Introduction of Graphical Analysis in 19th Century British Economics

The introduction of time-series graphs into British economics in the 19th century depended on the « timing » of history. This involved reconceptualizing history into events which were both comparable and measurable and standardized by time unit. Yet classical economists in Britain in the early 19th century viewed history as a set of heterogenous and complex events and statistical tables as giving unrelated facts. Both these attitudes had to be broken down before time-series graphs could be brought into use for revealing regularities in economic events by the century's end.

Identification and ethnic diversity underlie support for multicultural rights : a multilevel analysis in Bulgaria

Bulgaria is historically a multicultural society, composed of the Bulgarian (ethnic) majority and a number of ethnic minorities among which Bulgarian Turks and Roma are the largest. Both minority communities are stigmatized in contemporary Bulgaria, though to different degrees and for different reasons. Ethnic minorities' rights to preserve their culture, customs, and language are a topic of contentious debate. The purpose of this study was to examine individual- and context-level antecedents of the ethnic Bulgarian majority's support for multicultural rights of ethnic minorities. Multilevel regression analyses were conducted with International Social Survey Programme ISSP 2003 data (N = 920 in 28 Bulgarian districts). At the individual-level, an ethnic conception of the nation and anti-Roma symbolic prejudice were negatively related to support for multicultural rights, whereas national identification was positively related to the support of these rights. Over and above individual-level effects, and in line with recent extensions of intergroup contact theory, thepercentage ofBulgarianTurks withindistricts was positively related to support for multicultural rights. Importantly, support for multicultural rights was particularly high in districts characterized by ethnic diversity, that is, in districts with high proportions of both Bulgarian Turks and Roma. The beneficial effects of ethnic diversity and theoretical implications of findings are discussed.

The use of the likelihood ratio for evaluative and investigative purposes in comparative forensic handwriting examination

This paper extends previous research and discussion on the use of multivariate continuous data, which are about to become more prevalent in forensic science. As an illustrative example, attention is drawn here on the area of comparative handwriting examinations. Multivariate continuous data can be obtained in this field by analysing the contour shape of loop characters through Fourier analysis. This methodology, based on existing research in this area, allows one describe in detail the morphology of character contours throughout a set of variables. This paper uses data collected from female and male writers to conduct a comparative analysis of likelihood ratio based evidence assessment procedures in both, evaluative and investigative proceedings. While the use of likelihood ratios in the former situation is now rather well established (typically, in order to discriminate between propositions of authorship of a given individual versus another, unknown individual), focus on the investigative setting still remains rather beyond considerations in practice. This paper seeks to highlight that investigative settings, too, can represent an area of application for which the likelihood ratio can offer a logical support. As an example, the inference of gender of the writer of an incriminated handwritten text is forwarded, analysed and discussed in this paper. The more general viewpoint according to which likelihood ratio analyses can be helpful for investigative proceedings is supported here through various simulations. These offer a characterisation of the robustness of the proposed likelihood ratio methodology.

Characterizing aging in the human brainstem using quantitative multimodal MRI analysis.

Aging is ubiquitous to the human condition. The MRI correlates of healthy aging have been extensively investigated using a range of modalities, including volumetric MRI, quantitative MRI (qMRI), and diffusion tensor imaging. Despite this, the reported brainstem related changes remain sparse. This is, in part, due to the technical and methodological limitations in quantitatively assessing and statistically analyzing this region. By utilizing a new method of brainstem segmentation, a large cohort of 100 healthy adults were assessed in this study for the effects of aging within the human brainstem in vivo. Using qMRI, tensor-based morphometry (TBM), and voxel-based quantification (VBQ), the volumetric and quantitative changes across healthy adults between 19 and 75 years were characterized. In addition to the increased R2* in substantia nigra corresponding to increasing iron deposition with age, several novel findings were reported in the current study. These include selective volumetric loss of the brachium conjunctivum, with a corresponding decrease in magnetization transfer and increase in proton density (PD), accounting for the previously described "midbrain shrinkage." Additionally, we found increases in R1 and PD in several pontine and medullary structures. We consider these changes in the context of well-characterized, functional age-related changes, and propose potential biophysical mechanisms. This study provides detailed quantitative analysis of the internal architecture of the brainstem and provides a baseline for further studies of neurodegenerative diseases that are characterized by early, pre-clinical involvement of the brainstem, such as Parkinson's and Alzheimer's diseases.

Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project.

We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.