Prevalence and Clinical Outcomes for Patients With ALK-Positive Resected Stage I to III Adenocarcinoma: Results From the European Thoracic Oncology Platform Lungscape Project.

PURPOSE: The prevalence of anaplastic lymphoma kinase (ALK) gene fusion (ALK positivity) in early-stage non-small-cell lung cancer (NSCLC) varies by population examined and detection method used. The Lungscape ALK project was designed to address the prevalence and prognostic impact of ALK positivity in resected lung adenocarcinoma in a primarily European population. METHODS: Analysis of ALK status was performed by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) in tissue sections of 1,281 patients with adenocarcinoma in the European Thoracic Oncology Platform Lungscape iBiobank. Positive patients were matched with negative patients in a 1:2 ratio, both for IHC and for FISH testing. Testing was performed in 16 participating centers, using the same protocol after passing external quality assessment. RESULTS: Positive ALK IHC staining was present in 80 patients (prevalence of 6.2%; 95% CI, 4.9% to 7.6%). Of these, 28 patients were ALK FISH positive, corresponding to a lower bound for the prevalence of FISH positivity of 2.2%. FISH specificity was 100%, and FISH sensitivity was 35.0% (95% CI, 24.7% to 46.5%), with a sensitivity value of 81.3% (95% CI, 63.6% to 92.8%) for IHC 2+/3+ patients. The hazard of death for FISH-positive patients was lower than for IHC-negative patients (P = .022). Multivariable models, adjusted for patient, tumor, and treatment characteristics, and matched cohort analysis confirmed that ALK FISH positivity is a predictor for better overall survival (OS). CONCLUSION: In this large cohort of surgically resected lung adenocarcinomas, the prevalence of ALK positivity was 6.2% using IHC and at least 2.2% using FISH. A screening strategy based on IHC or H-score could be envisaged. ALK positivity (by either IHC or FISH) was related to better OS.

Theory of mind and cognitive processes in aging and Alzheimer type dementia: a systematic review.

OBJECTIVES: Theory of mind (ToM) performance in aging and dementia of the Alzheimer type (DAT) has been a growing interest of researchers and recently, theoretical trends in ToM development have led to a focus on determining the cognitive skills involved in ToM performance. The aim of the present review is to answer three main questions: How is ToM assessed in aging and DAT? How does ToM performance evolve in aging and DAT? Do cognitive processes influence ToM performance in aging and DAT? METHOD: A systematic review was conducted to provide a targeted overview of recent studies relating ToM performance with cognitive processes in aging and DAT. RESULTS: RESULTS suggest a decrease in ToM performance, more pronounced in complex ToM tasks. Moreover, the review points up the strong involvement of executive functions, especially inhibition, and reasoning skills in ToM task achievement. CONCLUSION: Current data suggest that the structure of ToM tasks itself could lead to poor performance, especially in populations with reduced cognitive abilities.

Hyperactivity and attention problems in a Swiss sample of school-aged children: effects of school achievement, child gender, and informants.

OBJECTIVE: The sensitivity and tolerance regarding ADHD symptoms obviously differ from one culture to another and according to the informants (parents, teachers, or children). This stimulates the comparison of data across informants and countries. METHOD: Parents and teachers of more than 1,000 school-aged Swiss children (5 to 17 years old) fill in Conners's questionnaires on ADHD. Children who are older than 10 years old also fill in a self-report questionnaire. Results are compared to data from a North American sample. RESULTS: Swiss parents and teachers tend to report more ADHD symptoms than American parents and teachers as far as the oldest groups of children are concerned. Interactions are evidenced between school achievement, child gender, and informants. A relatively low rate of agreement between informants is found. CONCLUSION: These results strengthen the importance to take into account all informants in the pediatric and the child psychiatry clinic, as well as in the epidemiological studies.

Self-paced Movement Intention Detection from Human Brain Signals: Invasive and Non-invasive EEG

Neural signatures of humans' movement intention can be exploited by future neuroprosthesis. We propose a method for detecting self-paced upper limb movement intention from brain signals acquired with both invasive and noninvasive methods. In the first study with scalp electroencephalograph (EEG) signals from healthy controls, we report single trial detection of movement intention using movement related potentials (MRPs) in a frequency range between 0.1 to 1 Hz. Movement intention can be detected above chance level (p<0.05) on average 460 ms before the movement onset with low detection rate during the on-movement intention period. Using intracranial EEG (iEEG) from one epileptic subject, we detect movement intention as early as 1500 ms before movement onset with accuracy above 90% using electrodes implanted in the bilateral supplementary motor area (SMA). The coherent results obtained with non-invasive and invasive method and its generalization capabilities across different days of recording, strengthened the theory that self-paced movement intention can be detected before movement initiation for the advancement in robot-assisted neurorehabilitation.

Application of real-time PCR for total airborne bacterial assessment : comparison with epifluorescence microscopy and culture-dependent methods

Traditional culture-dependent methods to quantify and identify airborne microorganisms are limited by factors such as short-duration sampling times and inability to count nonculturableor non-viable bacteria. Consequently, the quantitative assessment of bioaerosols is often underestimated. Use of the real-time quantitative polymerase chain reaction (Q-PCR) to quantify bacteria in environmental samples presents an alternative method, which should overcome this problem. The aim of this study was to evaluate the performance of a real-time Q-PCR assay as a simple and reliable way to quantify the airborne bacterial load within poultry houses and sewage treatment plants, in comparison with epifluorescencemicroscopy and culture-dependent methods. The estimates of bacterial load that we obtained from real-time PCR and epifluorescence methods, are comparable, however, our analysis of sewage treatment plants indicate these methods give values 270-290 fold greater than those obtained by the ''impaction on nutrient agar'' method. The culture-dependent method of air impaction on nutrient agar was also inadequate in poultry houses, as was the impinger-culture method, which gave a bacterial load estimate 32-fold lower than obtained by Q-PCR. Real-time quantitative PCR thus proves to be a reliable, discerning, and simple method that could be used to estimate airborne bacterial load in a broad variety of other environments expected to carry high numbers of airborne bacteria. [Authors]

The profiling of false identity documents: a promising method to fight identity fraud

Under the influence of intelligence-led policing models, crime analysis methods have known of important developments in recent years. Applications have been proposed in several fields of forensic science to exploit and manage various types of material evidence in a systematic and more efficient way. However, nothing has been suggested so far in the field of false identity documents.This study seeks to fill this gap by proposing a simple and general method for profiling false identity documents which aims to establish links based on their visual forensic characteristics. A sample of more than 200 false identity documents including French stolen blank passports, counterfeited driving licenses from Iraq and falsified Bulgarian driving licenses was gathered from nine Swiss police departments and integrated into an ad hoc developed database called ProfID. Links detected automatically and systematically through this database were exploited and analyzed to produce strategic and tactical intelligence useful to the fight against identity document fraud.The profiling and intelligence process established for these three types of false identity documents has confirmed its efficiency, more than 30% of documents being linked. Identity document fraud appears as a structured and interregional criminality, against which material and forensic links detected between false identity documents might serve as a tool for investigation.

Low income, community poverty and risk of end stage renal disease

BACKGROUND: The risk of end stage renal disease (ESRD) is increased among individuals with low income and in low income communities. However, few studies have examined the relation of both individual and community socioeconomic status (SES) with incident ESRD. METHODS: Among 23,314 U.S. adults in the population-based Reasons for Geographic and Racial Differences in Stroke study, we assessed participant differences across geospatially-linked categories of county poverty [outlier poverty, extremely high poverty, very high poverty, high poverty, neither (reference), high affluence and outlier affluence]. Multivariable Cox proportional hazards models were used to examine associations of annual household income and geospatially-linked county poverty measures with incident ESRD, while accounting for death as a competing event using the Fine and Gray method. RESULTS: There were 158 ESRD cases during follow-up. Incident ESRD rates were 178.8 per 100,000 person-years (105 py) in high poverty outlier counties and were 76.3 /105 py in affluent outlier counties, p trend = 0.06. In unadjusted competing risk models, persons residing in high poverty outlier counties had higher incidence of ESRD (which was not statistically significant) when compared to those persons residing in counties with neither high poverty nor affluence [hazard ratio (HR) 1.54, 95% Confidence Interval (CI) 0.75-3.20]. This association was markedly attenuated following adjustment for socio-demographic factors (age, sex, race, education, and income); HR 0.96, 95% CI 0.46-2.00. However, in the same adjusted model, income was independently associated with risk of ESRD [HR 3.75, 95% CI 1.62-8.64, comparing the < $20,000 income group to the > $75,000 group]. There were no statistically significant associations of county measures of poverty with incident ESRD, and no evidence of effect modification. CONCLUSIONS: In contrast to annual family income, geospatially-linked measures of county poverty have little relation with risk of ESRD. Efforts to mitigate socioeconomic disparities in kidney disease may be best appropriated at the individual level.

A rapid and effective vignetting correction for quantitative microscopy

Images acquired using optical microscopes are inherently subject to vignetting effects due to imperfect illumination and image acquisition. However, such vignetting effects hamper accurate extraction of quantitative information from biological images, leading to less effective image segmentation and increased noise in the measurements. Here, we describe a rapid and effective method for vignetting correction, which generates an estimate for a correction function from the background fluorescence without the need to acquire additional calibration images. We validate the usefulness of this algorithm using artificially distorted images as a gold standard for assessing the accuracy of the applied correction and then demonstrate that this correction method enables the reliable detection of biologically relevant variation in cell populations. A simple user interface called FlattifY was developed and integrated into the image analysis platform YeastQuant to facilitate easy application of vignetting correction to a wide range of images.

Alcohol consumption in late adolescence and early adulthood - where is the problem?

Risky single-occasion drinking (RSOD) is more common in late adolescence and early adulthood (approximately between the ages of 16 and 30) than in any other period in life. This is also the age when young people in Switzerland and many other European countries are legally allowed to buy and drink alcohol, but they usually do not yet have adult responsibilities. This paper reviews evidence from the international literature and provides examples of studies conducted in Switzerland demonstrating that (a) RSOD is by far most prevalent on Saturday evenings followed by Friday evenings, usually because young people go out and do not have any work or study responsibilities the next day; (b) RSOD results from drinking in private before going out ("predrinking") and accelerating the pace of drinking (i.e. increasing the number of drinks consumed per hour); (c) RSOD is often not accidental but purposeful,. to seek excitement, to have fun and to feel the effects of alcohol; (d) RSOD occurs predominantly outside the home, mostly in bars, pubs, discos or at special events and festivals; (e) RSOD often results in intended and unintended injuries and other acute consequences, which are leading risk factors for mortality and morbidity in this age group. Effective prevention strategies should include attempts to reduce opportunities to engage in heavy drinking as well as strategies to reduce its harmful consequences.

Care complexity, mood, and quality of life in liver pre-transplant patients.

RATIONALE: This study was intended to document the frequency of care complexity in liver transplant candidates, and its association with mood disturbance and poor health-related quality of life (HRQoL). METHODS: Consecutive patients fulfilling inclusion criteria, recruited in three European hospitals, were assessed with INTERMED, a reliable and valid method for the early assessment of bio-psychosocial health risks and needs. Blind to the results, they were also assessed with the Hospital Anxiety and Depression Scale (HADS). HRQoL was documented with the EuroQol and the SF36. Statistical analysis included multivariate and multilevel techniques. RESULTS: Among patients fulfilling inclusion criteria, 60 patients (75.9%) completed the protocol and 38.3% of them were identified as "complex" by INTERMED, but significant between-center differences were found. In support of the working hypothesis, INTERMED scores were significantly associated with all measures of both the SF36 and the EuroQol, and also with the HADS. A one point increase in the INTERMED score results in a reduction in 0.93 points in EuroQol and a 20% increase in HADS score. CONCLUSIONS: INTERMED-measured case complexity is frequent in liver transplant candidates but varies widely between centers. The use of this method captures in one instrument multiple domains of patient status, including mood disturbances and reduced HRQoL.

Method for performing cerebral perfusion-weighted MRI in neonates

Cerebral perfusion-weighted imaging (PWI) in neonates is known to be technically difficult and there are very few published studies on its use in preterm infants. In this paper, we describe one convenient method to perform PWI in neonates, a method only recently used in newborns. A device was used to manually inject gadolinium contrast material intravenously in an easy, quick and reproducible way. We studied 28 newborn infants, with various gestational ages and weights, including both normal infants and those suffering from different brain pathologies. A signal intensity-time curve was obtained for each infant, allowing us to build perfusion maps. This technique offered a fast and easy method to manually inject a bolus gadolinium contrast material, which is essential in performing PWI in neonates. Cerebral PWI is technically feasible and reproducible in neonates of various gestational age and with various pathologies.

Development of motor speed and associated movements from 5 to 18 years.

AIM: To study the development of motor speed and associated movements in participants aged 5 to 18 years for age, sex, and laterality. METHOD: Ten motor tasks of the Zurich Neuromotor Assessment (repetitive and alternating movements of hands and feet, repetitive and sequential finger movements, the pegboard, static and dynamic balance, diadochokinesis) were administered to 593 right-handed participants (286 males, 307 females). RESULTS: A strong improvement with age was observed in motor speed from age 5 to 10, followed by a levelling-off between 12 and 18 years. Simple tasks and the pegboard matured early and complex tasks later. Simple tasks showed no associated movements beyond early childhood; in complex tasks associated movements persisted until early adulthood. The two sexes differed only marginally in speed, but markedly in associated movements. A significant laterality (p<0.001) in speed was found for all tasks except for static balance; the pegboard was most lateralized, and sequential finger movements least. Associated movements were lateralized only for a few complex tasks. We also noted a substantial interindividual variability. INTERPRETATION: Motor speed and associated movements improve strongly in childhood, weakly in adolescence, and are both of developmental relevance. Because they correlate weakly, they provide complementary information.

A fast 3D approach for coronary MRA.

Two-dimensional (2D)-breath-hold coronary magnetic resonance angiography (MRA) has been shown to be a fast and reliable method to depict the proximal coronary arteries. Recent developments, however, allow for free-breathing navigator gated and navigator corrected three-dimensional (3D) coronary MRA. These 3D approaches have potential for improved signal-to-noise ratio (SNR) and allow for the acquisition of adjacent thin slices without the misregistration problems known from 2D approaches. Still, a major impediment of a 3D acquisition is the increased scan time. The purpose of this study was the implementation of a free-breathing navigator gated and corrected ultra-fast 3D coronary MRA technique, which allows for scan times of less than 5 minutes. Twelve healthy adult subjects were examined in the supine position using a navigator gated and corrected ECG triggered ultra-fast 3D interleaved gradient echo planar imaging sequence (TFE-EPI). A 3D slab, consisting of 20 slices with a reconstructed slice thickness of 1.5 mm, was acquired with free-breathing. The diastolic TFE-EPI acquisition block was preceded by a T2prep pre-pulse, a diaphragmatic navigator pulse, and a fat suppression pre-pulse. With a TR of 19 ms and an effective TE of 5.4 ms, the duration of the data acquisition window duration was 38 ms. The in-plane spatial resolution was 1.0-1.3 mm*1.5-1.9 mm. In all cases, the entire left main (LM) and extensive portions of the left anterior descending (LAD) and right coronary artery (RCA) could be visualized with an average scan time for the entire 3D-volume data set of 2:57 +/- 0:51 minutes. Average contiguous vessel length visualized was 53 +/- 11 mm (range: 42 to 75 mm) for the LAD and 84 +/- 14 mm (range: 62 to 112 mm) for the RCA. Contrast-to-noise between coronary blood and myocardium was 5.0 +/- 2.3 for the LM/LAD and 8.0 +/- 2.9 for the RCA, resulting in an excellent suppression of myocardium. We present a new approach for free-breathing 3D coronary MRA, which allows for scan times superior to corresponding 2D coronary MRA approaches, and which takes advantage of the enhanced SNR of 3D acquisitions and the post-processing benefits of thin adjacent slices. The robust image quality and the short average scanning time suggest that this approach may be useful for screening the major coronary arteries or identification of anomalous coronary arteries. J. Magn. Reson. Imaging 1999;10:821-825.

Therapeutic drug monitoring of seven psychotropic drugs and four metabolites in human plasma by HPLC-MS.

A simple and sensitive LC-MS method was developed and validated for the simultaneous quantification of aripiprazole (ARI), atomoxetine (ATO), duloxetine (DUL), clozapine (CLO), olanzapine (OLA), sertindole (STN), venlafaxine (VEN) and their active metabolites dehydroaripiprazole (DARI), norclozapine (NCLO), dehydrosertindole (DSTN) and O-desmethylvenlafaxine (OVEN) in human plasma. The above mentioned compounds and the internal standard (remoxipride) were extracted from 0.5 mL plasma by solid-phase extraction (mix mode support). The analytical separation was carried out on a reverse phase liquid chromatography at basic pH (pH 8.1) in gradient mode. All analytes were monitored by MS detection in the single ion monitoring mode and the method was validated covering the corresponding therapeutic range: 2-200 ng/mL for DUL, OLA, and STN, 4-200 ng/mL for DSTN, 5-1000 ng/mL for ARI, DARI and finally 2-1000 ng/mL for ATO, CLO, NCLO, VEN, OVEN. For all investigated compounds, good performance in terms of recoveries, selectivity, stability, repeatability, intermediate precision, trueness and accuracy, was obtained. Real patient plasma samples were then successfully analysed.

A systematic review of longitudinal population-based studies on the predictors of smoking cessation in adolescent and young adult smokers.

OBJECTIVE: To describe the determinants of self-initiated smoking cessation of duration of at least 6 months as identified in longitudinal population-based studies of adolescent and young adult smokers. METHODS: A systematic search of the PubMed and EMBASE databases using smoking, tobacco, cessation, quit and stop as keywords was performed. Limits included articles related to humans, in English, published between January 1984 and August 2010, and study population aged 10-29 years. A total of 4502 titles and 871 abstracts were reviewed independently by 2 and 3 reviewers, respectively. Nine articles were retained for data abstraction. Data on study location, timeframe, duration of follow-up, number of data collection points, sample size, age/grade of participants, number of quitters, smoking status at baseline, definition of cessation, covariates and analytic method were abstracted from each article. The number of studies that reported a statistically significant association between each determinant investigated and cessation were tabulated, from among all studies that assessed the determinant. RESULTS: Despite heterogeneity in methods across studies, five factors robustly predicted quitting across studies in which the factor was investigated: not having friends who smoke, not having intentions to smoke in the future, resisting peer pressure to smoke, being older at first use of cigarette and having negative beliefs about smoking. CONCLUSIONS: The literature on longitudinal predictors of cessation in adolescent and young adult smokers is not well developed. Cessation interventions for this population will remain less than optimally effective until there is a solid evidence base on which to develop interventions.