Evaluation of organ-specific peripheral doses after 2-dimensional, 3-dimensional and hybrid intensity modulated radiation therapy for breast cancer based on Monte Carlo and convolution/superposition algorithms: implications for secondary cancer risk assessment.

To make a comprehensive evaluation of organ-specific out-of-field doses using Monte Carlo (MC) simulations for different breast cancer irradiation techniques and to compare results with a commercial treatment planning system (TPS). Three breast radiotherapy techniques using 6MV tangential photon beams were compared: (a) 2DRT (open rectangular fields), (b) 3DCRT (conformal wedged fields), and (c) hybrid IMRT (open conformal+modulated fields). Over 35 organs were contoured in a whole-body CT scan and organ-specific dose distributions were determined with MC and the TPS. Large differences in out-of-field doses were observed between MC and TPS calculations, even for organs close to the target volume such as the heart, the lungs and the contralateral breast (up to 70% difference). MC simulations showed that a large fraction of the out-of-field dose comes from the out-of-field head scatter fluence (>40%) which is not adequately modeled by the TPS. Based on MC simulations, the 3DCRT technique using external wedges yielded significantly higher doses (up to a factor 4-5 in the pelvis) than the 2DRT and the hybrid IMRT techniques which yielded similar out-of-field doses. In sharp contrast to popular belief, the IMRT technique investigated here does not increase the out-of-field dose compared to conventional techniques and may offer the most optimal plan. The 3DCRT technique with external wedges yields the largest out-of-field doses. For accurate out-of-field dose assessment, a commercial TPS should not be used, even for organs near the target volume (contralateral breast, lungs, heart).

More is not always better-comparison of three instruments measuring volume of drinking in a sample of young men and their association with consequences

OBJECTIVE: In general population survey instruments that measure volume of drinking, additional questions and shorter reference periods yield higher volumes. Comparison studies have focused on volume but not on associations between volume and consequences. METHOD: From a cohort study on substance use risk factors (Cohort Study on Substance Use Risk Factors [C-SURF]), baseline data were analyzed for 5,074 young (approximately 20-year-old) men who were drinkers in the past 12 months. Volume of drinking was measured by a generic quantity-frequency (QF) instrument, an extended QF (separately for weekends and weekdays) instrument with 12-months recall, and a retrospective past-week diary. Associations of consequences with and without attribution of alcohol as a cause, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), criteria for dependence, and DSM-5 alcohol use disorder in the past 12 months were analyzed. RESULTS: The generic QF measure resulted in lower volume compared with either the extended QF measure (more questions) or the retrospective diary (the most questions and the shortest recall period). For outcomes, however, the extended QF assessment performed the best and the diary the worst. CONCLUSIONS: Higher volume yields are not always better regarding associations with outcomes. The extended QF instrument better captures the variability of drinking. The retrospective diary performs poorly for associations because of the mismatch with the recall period for past-12-months consequences and the potential for misclassification of past-week abstainers and heavy drinkers because of an uncommon past week. Diaries are not recommended for research investigating individual associations between exposure and outcomes in young populations if consequences are measured with a sufficiently long interval to capture rare consequences. (J. Stud. Alcohol Drugs, 75, 880-888, 2014).

IEF pattern classification-derived criteria for the identification of epoetin-delta in urine.

Epoetin-delta (Dynepo Shire Pharmaceuticals, Basing stoke, UK) is a synthetic form of erythropoietin (EPO) whose resemblance with endogenous EPO makes it hard to identify using the classical identification criteria. Urine samples collected from six healthy volunteers treated with epoetin-delta injections and from a control population were immuno-purified and analyzed with the usual IEF method. On the basis of the EPO profiles integration, a linear multivariate model was computed for discriminant analysis. For each sample, a pattern classification algorithm returned a bands distribution and intensity score (bands intensity score) saying how representative this sample is of one of the two classes, positive or negative. Effort profiles were also integrated in the model. The method yielded a good sensitivity versus specificity relation and was used to determine the detection window of the molecule following multiple injections. The bands intensity score, which can be generalized to epoetin-alpha and epoetin-beta, is proposed as an alternative criterion and a supplementary evidence for the identification of EPO abuse.

Structural Validity of the Wechsler Intelligence Scale for Children (WISC-IV) in a French-speaking Swiss sample

The Wechsler Intelligence Scale for Children-fourth edition (i.e. WISC-IV) recognizes a four-factor scoring structure in addition to the Full Scale IQ (FSIQ) score: Verbal Comprehension (VCI), Perceptual Reasoning (PRI), Working Memory (WMI), and Processing Speed (PSI) indices. However, several authors suggested that models based on the Cattell-Horn-Carroll (CHC) theory with 5 or 6 factors provided a better fit to the data than does the current four-factor solution. By comparing the current four-factor structure to CHC-based models, this research aimed to investigate the factorial structure and the constructs underlying the WISC-IV subtest scores with French-speaking Swiss children (N = 249). To deal with this goal, confirmatory factor analyses (CFAs) were conducted. Results showed that a CHC-based model with five factors better fitted the French-Swiss data than did the current WISC-IV scoring structure. All together, these results support the hypothesis of the appropriateness of the CHC model with French-speaking children.

New perspectives in the use of ink evidence in forensic science: Part II. Development and testing of mathematical algorithms for the automatic comparison of ink samples analysed by HPTLC

In the first part of this research, three stages were stated for a program to increase the information extracted from ink evidence and maximise its usefulness to the criminal and civil justice system. These stages are (a) develop a standard methodology for analysing ink samples by high-performance thin layer chromatography (HPTLC) in reproducible way, when ink samples are analysed at different time, locations and by different examiners; (b) compare automatically and objectively ink samples; and (c) define and evaluate theoretical framework for the use of ink evidence in forensic context. This report focuses on the second of the three stages. Using the calibration and acquisition process described in the previous report, mathematical algorithms are proposed to automatically and objectively compare ink samples. The performances of these algorithms are systematically studied for various chemical and forensic conditions using standard performance tests commonly used in biometrics studies. The results show that different algorithms are best suited for different tasks. Finally, this report demonstrates how modern analytical and computer technology can be used in the field of ink examination and how tools developed and successfully applied in other fields of forensic science can help maximising its impact within the field of questioned documents.

Quantifying ChIP-seq data: a spiking method providing an internal reference for sample-to-sample normalization.

Chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) experiments are widely used to determine, within entire genomes, the occupancy sites of any protein of interest, including, for example, transcription factors, RNA polymerases, or histones with or without various modifications. In addition to allowing the determination of occupancy sites within one cell type and under one condition, this method allows, in principle, the establishment and comparison of occupancy maps in various cell types, tissues, and conditions. Such comparisons require, however, that samples be normalized. Widely used normalization methods that include a quantile normalization step perform well when factor occupancy varies at a subset of sites, but may miss uniform genome-wide increases or decreases in site occupancy. We describe a spike adjustment procedure (SAP) that, unlike commonly used normalization methods intervening at the analysis stage, entails an experimental step prior to immunoprecipitation. A constant, low amount from a single batch of chromatin of a foreign genome is added to the experimental chromatin. This "spike" chromatin then serves as an internal control to which the experimental signals can be adjusted. We show that the method improves similarity between replicates and reveals biological differences including global and largely uniform changes.

Health at work and risk factors related to ergonomics: some results from the Swiss sample of the 4th European working conditions survey

Introduction The European Foundation for the improvement of living and working conditions conducts a survey every 5 years since 1990. The foundation also offers the possibility to non-EU countries to be included in the survey: in 2005, Switzerland took part for the first time in the fourth edition of this survey. The Institute for Work and Health (IST) has been associated to the Swiss project conducted under the leadership of the SECO and the Fachhochschule Nordwestschweiz. The survey covers different aspects of work like job characteristics and employment conditions, health and safety, work organization, learning and development opportunities, and the balance between working and non-working life (Parent-Thirion, Fernandez Macias, Hurley, & Vermeylen, 2007). More particularly, one question assesses the worker's self-perception of the effects of work on health. We identified (for the Swiss sample) several factors affecting the risk to report health problems caused by work. The Swiss sample includes 1040 respondents. Selection of participants was based on a random multi-stage sampling and was carried out by M.I.S Trend S.A. (Lausanne). Participation rate was 59%. The database was weighted by household size, gender, age, region of domicile, occupational group, and economic sector. Specially trained interviewers carried out the interviews at the respondents home. The survey was carriedout between the 19th of September 2005 and the 30th of November 2005. As detailed in (Graf et al., 2007), 31% of the Swiss respondents identify work as the cause of health problems they experience. Most frequently reported health problems include back pain (18%), stress (17%), muscle pain (13%), and overall fatigue (11%). Ergonomic aspects associated with higher risk of reporting health problems caused by work include frequent awkward postures (odds ratio [OR] 4.7, 95% confidence interval [CI] 3.1 to 5.4), tasks involving lifting heavy loads (OR 2.7, 95% CI 2.0 to 3.6) or lifting people (OR 2.2, 95% CI 1.4 to 3.5), standing or walking (OR 1.4, 95% CI 1.1 to 1.9), as well as repetitive movements (OR 1.7, 95% CI 1.3 to 2.3). These results highlight the need to continue and intensify the prevention of work related health problems in occupations characterized by risk factors related to ergonomics.

Gender differences in premorbid, entry, treatment, and outcome characteristics in a treated epidemiological sample of 661 patients with first episode psychosis.

OBJECTIVES: Gender differences in psychotic disorder have been observed in terms of illness onset and course; however, past research has been limited by inconsistencies between studies and the lack of epidemiological representative of samples assessed. Thus, the aim of this study was to elucidate gender differences in a treated epidemiological sample of patients with first episode psychosis (FEP). METHODS: A medical file audit was used to collect data on premorbid, entry, treatment and 18-month outcome characteristics of 661 FEP consecutive patients treated at the Early Psychosis Prevention and Intervention Centre (EPPIC), Melbourne, Australia. RESULTS: Prior to onset of psychosis, females were more likely to have a history of suicide attempts (p=.011) and depression (p=.001). At service entry, females were more likely to have depressive symptoms (p=.007). Conversely, males had marked substance use problems that were evident prior to admission (p<.001) and persisted through treatment (p<.001). At service entry, males also experienced more severe psychopathology (p<.001) and lower levels of functioning (GAF, p=.008; unemployment/not studying p=.004; living with family, p=.003). Treatment non-compliance (p<.001) and frequent hospitalisations (p=.047) were also common for males with FEP. At service discharge males had significantly lower levels of functioning (GAF, p=.008; unemployment/not studying p=.040; living with family, p=.001) compared to females with FEP. CONCLUSIONS: Gender differences are evident in illness course of patients with FEP, particularly with respect to past history of psychopathology and functioning at presentation and at service discharge. Strategies to deal with these gender differences need to be considered in early intervention programs.

Tackling self-selection into treatment and self-selection into the sample biases in VAA research

Self‐selection into treatment and self‐selection into the sample are major concerns of VAA research and need to be controlled for if the aim is to deduce causal effects from VAA use in observational data. This paper focuses on the methodological aspects of VAA research and outlines omnipresent endogeneity issues, partly imposed through unobserved factors that affect both whether individuals chose to use VAAs and their electoral behavior. We promote using Heckman selection models and apply various versions of the model to data from the Swiss electorate and smartvote users in order to see to what extent selection biases interfere with the estimated effects of interest.

Metabolic equivalent: one size does not fit all.

The metabolic equivalent (MET) is a widely used physiological concept that represents a simple procedure for expressing energy cost of physical activities as multiples of resting metabolic rate (RMR). The value equating 1 MET (3.5 ml O2 x kg(-1) x min(-1) or 1 kcal x kg(-1) x h(-1)) was first derived from the resting O2 consumption (VO2) of one person, a 70-kg, 40-yr-old man. Given the extensive use of MET levels to quantify physical activity level or work output, we investigated the adequacy of this scientific convention. Subjects consisted of 642 women and 127 men, 18-74 yr of age, 35-186 kg in weight, who were weight stable and healthy, albeit obese in some cases. RMR was measured by indirect calorimetry using a ventilated hood system, and the energy cost of walking on a treadmill at 5.6 km/h was measured in a subsample of 49 men and 49 women (26-45 kg/m2; 29-47 yr). Average VO2 and energy cost corresponding with rest (2.6 +/- 0.4 ml O2 x kg(-1) x min(-1) and 0.84 +/- 0.16 kcal x kg(-1) x h(-1), respectively) were significantly lower than the commonly accepted 1-MET values of 3.5 ml O2 x kg(-1) x min(-1) and 1 kcal x kg(-1) x h(-1), respectively. Body composition (fat mass and fat-free mass) accounted for 62% of the variance in resting VO2 compared with age, which accounted for only 14%. For a large heterogeneous sample, the 1-MET value of 3.5 ml O2 x kg(-1) x min(-1) overestimates the actual resting VO2 value on average by 35%, and the 1-MET of 1 kcal/h overestimates resting energy expenditure by 20%. Using measured or predicted RMR (ml O2 x kg(-1) x min(-1) or kcal x kg(-1) x h(-1)) as a correction factor can appropriately adjust for individual differences when estimating the energy cost of moderate intensity walking (5.6 km/h).

Swain: Stata module to correct the SEM chi-square overidentification test in small sample sizes or complex models. Statistical Software Components S457617, Boston College Department of Economics.

Swain corrects the chi-square overidentification test (i.e., likelihood ratio test of fit) for structural equation models whethr with or without latent variables. The chi-square statistic is asymptotically correct; however, it does not behave as expected in small samples and/or when the model is complex (cf. Herzog, Boomsma, & Reinecke, 2007). Thus, particularly in situations where the ratio of sample size (n) to the number of parameters estimated (p) is relatively small (i.e., the p to n ratio is large), the chi-square test will tend to overreject correctly specified models. To obtain a closer approximation to the distribution of the chi-square statistic, Swain (1975) developed a correction; this scaling factor, which converges to 1 asymptotically, is multiplied with the chi-square statistic. The correction better approximates the chi-square distribution resulting in more appropriate Type 1 reject error rates (see Herzog & Boomsma, 2009; Herzog, et al., 2007).