Effects of computing parameters and measurement locations on the estimation of 3D NPS in non-stationary MDCT images.

The goal of this study was to investigate the impact of computing parameters and the location of volumes of interest (VOI) on the calculation of 3D noise power spectrum (NPS) in order to determine an optimal set of computing parameters and propose a robust method for evaluating the noise properties of imaging systems. Noise stationarity in noise volumes acquired with a water phantom on a 128-MDCT and a 320-MDCT scanner were analyzed in the spatial domain in order to define locally stationary VOIs. The influence of the computing parameters in the 3D NPS measurement: the sampling distances bx,y,z and the VOI lengths Lx,y,z, the number of VOIs NVOI and the structured noise were investigated to minimize measurement errors. The effect of the VOI locations on the NPS was also investigated. Results showed that the noise (standard deviation) varies more in the r-direction (phantom radius) than z-direction plane. A 25 × 25 × 40 mm(3) VOI associated with DFOV = 200 mm (Lx,y,z = 64, bx,y = 0.391 mm with 512 × 512 matrix) and a first-order detrending method to reduce structured noise led to an accurate NPS estimation. NPS estimated from off centered small VOIs had a directional dependency contrary to NPS obtained from large VOIs located in the center of the volume or from small VOIs located on a concentric circle. This showed that the VOI size and location play a major role in the determination of NPS when images are not stationary. This study emphasizes the need for consistent measurement methods to assess and compare image quality in CT.

Country actions to meet UN commitments on non-communicable diseases: a stepwise approach.

Strong leadership from heads of state is needed to meet national commitments to the UN political declaration on non-communicable diseases (NCDs) and to achieve the goal of a 25% reduction in premature NCD mortality by 2025 (the 25 by 25 goal). A simple, phased, national response to the political declaration is suggested, with three key steps: planning, implementation, and accountability. Planning entails mobilisation of a multisectoral response to develop and support the national action plan, and to build human, financial, and regulatory capacity for change. Implementation of a few priority and feasible cost-effective interventions for the prevention and treatment of NCDs will achieve the 25 by 25 goal and will need only few additional financial resources. Accountability incorporates three dimensions: monitoring of progress, reviewing of progress, and appropriate responses to accelerate progress. A national NCD commission or equivalent, which is independent of government, is needed to ensure that all relevant stakeholders are held accountable for the UN commitments to NCDs.

Predictors of substance use reduction in an epidemiological first-episode psychosis cohort.

AIM: To assess the predictors of a significant decrease or cessation of substance use (SU) in a treated epidemiological cohort of first-episode psychosis (FEP) patients. METHOD: Participants were FEP patients of the Early Psychosis Prevention and Intervention Centre in Australia. Patients' medical files were reviewed using a standardized file audit. Data on 432 patients with FEP and baseline co-morbid substance use disorder (SUD) were available for analysis. Predictors of reduction/cessation of SU at follow up were examined using logistic regression analyses. RESULTS: In univariate analyses, a reduction/cessation of SU was predicted by baseline measures reflecting higher education, employment, accommodation with others, cannabis use disorder (CUD) only (rather than poly-SUDs), better global functioning and better premorbid social and occupational functioning, later age at onset of psychosis, and a diagnosis of non-affective psychosis. In multivariate analysis, CUD alone and better premorbid social and occupational functioning remained significant predictors. CONCLUSIONS: Addressing SUDs and social and occupational goals in people with FEP may offer opportunities to prevent SUDs becoming more severe or entrenched. Further longitudinal research on recovery from SU and FEP is needed to disentangle directions of influence and identify key targets for intervention.

Postprandial thermogenesis in lactating and non-lactating women from The Gambia.

Postprandial thermogenesis was assessed by indirect calorimetry in 32 Gambian women classified into three groups as follows: 12 non-pregnant non-lactating and 10 lactating women studied during the dry season and 10 lactating women studied during the rainy season. The test meal consisted of a typical Gambian breakfast and its energy content corresponded to 30% of the individual's resting metabolic rate (RMR)/24 h. During the dry season, the postprandial thermogenesis of the lactating women averaged 6.0 +/- 0.4% of the test meal energy content and was similar to that observed in the non-pregnant non-lactating women studied during the same season (5.8 +/- 0.3%). In contrast, the postprandial thermogenesis of lactating women studied during the rainy, nutritionally unfavourable season was found to be significantly lower (4.9 +/- 0.5%). There was no significant difference in the pre- and postprandial respiratory quotients among groups. This leads to the conclusion that lactation does not alter the thermogenic response to food and that the reduction in postprandial thermogenesis observed in lactating women during the wet season constitutes an adaptive response to energy deficit allowing a saving of energy in periods of food restriction.

Inhibition of the shade avoidance response by formation of non-DNA binding bHLH heterodimers.

In shade-intolerant plants such as Arabidopsis, a reduction in the red/far-red (R/FR) ratio, indicative of competition from other plants, triggers a suite of responses known as the shade avoidance syndrome (SAS). The phytochrome photoreceptors measure the R/FR ratio and control the SAS. The phytochrome-interacting factors 4 and 5 (PIF4 and PIF5) are stabilized in the shade and are required for a full SAS, whereas the related bHLH factor HFR1 (long hypocotyl in FR light) is transcriptionally induced by shade and inhibits this response. Here we show that HFR1 interacts with PIF4 and PIF5 and limits their capacity to induce the expression of shade marker genes and to promote elongation growth. HFR1 directly inhibits these PIFs by forming non-DNA-binding heterodimers with PIF4 and PIF5. Our data indicate that PIF4 and PIF5 promote SAS by directly binding to G-boxes present in the promoter of shade marker genes, but their action is limited later in the shade when HFR1 accumulates and forms non-DNA-binding heterodimers. This negative feedback loop is important to limit the response of plants to shade.

Fluoxetine augmentation in citalopram non-responders: pharmacokinetic and clinical consequences.

In an open trial 11 in-patients with a major depressive episode (ICD-10), extensive metabolizers of mephenytoin (CYP2C19) and dextromethorphan (CYP2D6) and who were non-responders to a 3-wk pretreatment with 40 mg/d citalopram (Cit), were co-medicated for 7 wk (days 0-49) with fluoxetine (Fluox) (10 mg/d). Plasma concentrations of S-Cit and R-Cit significantly increased from day 0 (means+/-S.D.: 28+/-9 and 47+/-11 &mgr;g/l, respectively) to day 49 (58+/-12 and 72+/-21 &mgr;g/l, respectively) (p & 0.01 for each comparison), and the S-Cit/R-Cit ratio increased from 0.61+/-0.16 to 0.82+/-0.12 (p & 0.01). Therefore, Fluox increases the pharmacologically more active S-Cit (in comparison with R-Cit) with some stereoselectivity, most probably by inhibition of CYP2D6 and CYP3A4. Eight of the 11 patients showed clinical improvement (reduction > 50% of the MADRS score) and the combined treatment was generally well tolerated.

Motion artifact reduction and vessel enhancement for free-breathing navigator-gated coronary MRA using 3D k-space reordering.

Breathing-induced bulk motion of the myocardium during data acquisition may cause severe image artifacts in coronary magnetic resonance angiography (MRA). Current motion compensation strategies include breath-holding or free-breathing MR navigator gating and tracking techniques. Navigator-based techniques have been further refined by the applications of sophisticated 2D k-space reordering techniques. A further improvement in image quality and a reduction of relative scanning duration may be expected from a 3D k-space reordering scheme. Therefore, a 3D k-space reordered acquisition scheme including a 3D navigator gated and corrected segmented k-space gradient echo imaging sequence for coronary MRA was implemented. This new zonal motion-adapted acquisition and reordering technique (ZMART) was developed on the basis of a numerical simulation of the Bloch equations. The technique was implemented on a commercial 1.5T MR system, and first phantom and in vivo experiments were performed. Consistent with the results of the theoretical findings, the results obtained in the phantom studies demonstrate a significant reduction of motion artifacts when compared to conventional (non-k-space reordered) gating techniques. Preliminary in vivo findings also compare favorably with the phantom experiments and theoretical considerations. Magn Reson Med 45:645-652, 2001.

Cannabis Users Identifying Themselves as Non-Cigarette Smokers : Who Are They?

Introduction and Aims. About 20% of cannabis consumers report not smoking cigarettes. Studies that have compared cannabis and cigarette smokers, cigarette smokers, and cannabis users who do not smoke cigarettes (CNSs) have shown that CNSs have better outcomes across a range of indicators compared to the others. Therefore, we conducted a qualitative study to determine why CNSs did not smoke cigarettes and how they managed to resist cigarette smoking in order to better inform prevention efforts. Design and Methods. We conducted five focus groups (FG) with a total of 19 CNSs between ages 16 and 25. A narrative analysis of FGs was conducted using qualitative analysis software. Results. CNSs' non-smoking choice was rooted in a negative opinion of cigarettes and a harm-reduction strategy. They were unique cases within their peer groups, but there were no CNSs groups. All participants were confronted to the mulling paradox. Discussion and Conclusions. While tobacco-use prevention seems to have been successful, CNSs need to be informed of harmful consequences of chronic cannabis use. Given their habit of adding tobacco to cannabis, CNSs need to be alerted that they may be nicotine dependent even though they do not smoke tobacco on its own. This exploratory study brings essential insight concerning this specific population of cannabis consumers which future research should continue to develop.

Towards high-quality simultaneous EEG-fMRI at 7T: Detection and reduction of EEG artifacts due to head motion.

The enhanced functional sensitivity offered by ultra-high field imaging may significantly benefit simultaneous EEG-fMRI studies, but the concurrent increases in artifact contamination can strongly compromise EEG data quality. In the present study, we focus on EEG artifacts created by head motion in the static B0 field. A novel approach for motion artifact detection is proposed, based on a simple modification of a commercial EEG cap, in which four electrodes are non-permanently adapted to record only magnetic induction effects. Simultaneous EEG-fMRI data were acquired with this setup, at 7T, from healthy volunteers undergoing a reversing-checkerboard visual stimulation paradigm. Data analysis assisted by the motion sensors revealed that, after gradient artifact correction, EEG signal variance was largely dominated by pulse artifacts (81-93%), but contributions from spontaneous motion (4-13%) were still comparable to or even larger than those of actual neuronal activity (3-9%). Multiple approaches were tested to determine the most effective procedure for denoising EEG data incorporating motion sensor information. Optimal results were obtained by applying an initial pulse artifact correction step (AAS-based), followed by motion artifact correction (based on the motion sensors) and ICA denoising. On average, motion artifact correction (after AAS) yielded a 61% reduction in signal power and a 62% increase in VEP trial-by-trial consistency. Combined with ICA, these improvements rose to a 74% power reduction and an 86% increase in trial consistency. Overall, the improvements achieved were well appreciable at single-subject and single-trial levels, and set an encouraging quality mark for simultaneous EEG-fMRI at ultra-high field.

Non-invasive prenatal testing for aneuploidy and beyond: challenges of responsible innovation in prenatal screening.

This paper contains a joint ESHG/ASHG position document with recommendations regarding responsible innovation in prenatal screening with non-invasive prenatal testing (NIPT). By virtue of its greater accuracy and safety with respect to prenatal screening for common autosomal aneuploidies, NIPT has the potential of helping the practice better achieve its aim of facilitating autonomous reproductive choices, provided that balanced pretest information and non-directive counseling are available as part of the screening offer. Depending on the health-care setting, different scenarios for NIPT-based screening for common autosomal aneuploidies are possible. The trade-offs involved in these scenarios should be assessed in light of the aim of screening, the balance of benefits and burdens for pregnant women and their partners and considerations of cost-effectiveness and justice. With improving screening technologies and decreasing costs of sequencing and analysis, it will become possible in the near future to significantly expand the scope of prenatal screening beyond common autosomal aneuploidies. Commercial providers have already begun expanding their tests to include sex-chromosomal abnormalities and microdeletions. However, multiple false positives may undermine the main achievement of NIPT in the context of prenatal screening: the significant reduction of the invasive testing rate. This document argues for a cautious expansion of the scope of prenatal screening to serious congenital and childhood disorders, only following sound validation studies and a comprehensive evaluation of all relevant aspects. A further core message of this document is that in countries where prenatal screening is offered as a public health programme, governments and public health authorities should adopt an active role to ensure the responsible innovation of prenatal screening on the basis of ethical principles. Crucial elements are the quality of the screening process as a whole (including non-laboratory aspects such as information and counseling), education of professionals, systematic evaluation of all aspects of prenatal screening, development of better evaluation tools in the light of the aim of the practice, accountability to all stakeholders including children born from screened pregnancies and persons living with the conditions targeted in prenatal screening and promotion of equity of access.

"Role of long non-coing RNAs in the stressed heart". Wisper : a novel cardiac fibroblast-enriched IncRNA that modulate fibrosis in the failing heart

LncRNAs are transcripts greater than 200 nucleotides in length with no apparent coding potential. They exert important regulatory functions in the genome. Their role in cardiac fibrosis is however unexplored. To identify IncRNAs that could modulate cardiac fibrosis, we profiled the long non-coding transcriptome in the infarcted mouse heart, and identified 1500 novel IncRNAs. These IncRNAs have unique characteristics such as high tissue and cell type specificity. Their expression is highly correlated with parameters of cardiac dimensions and function. The majority of these novel IncRNAs are conserved in human. Importantly, human IncRNAs appear to be differentially expressed in heart disease. Using a computational pipeline, we identified a super-enhancer-associated IncRNA, which is dynamically expressed after myocardial infarction. We named this particular transcript Wisper for «Wisp2 super-enhancer- derived IncRNA ». Interestingly, Wisper expression is overexpressed in cardiac fibroblasts as compared to cardiomyocytes or to fibroblasts isolated from other organs than the heart. The importance of Wisper in the biology of fibroblasts was demonstrated in knockdown experiments. Differentiation of cardiac fibroblast into myofibroblasts in vitro is significantly impaired upon Wisper knockdown. Wisper downregulation in cardiac fibroblasts results in a dramatic reduction of fibrotic gene expression, a diminished cell proliferation and an increase in apoptotic cell death. In vivo, depletion of Wisper during the acute phase of the response to infarction is detrimental via increasing the risk of cardiac rupture. On the other hand, Wisper knockdown following infarction in a prevention study reduces fibrosis and preserves cardiac function. Since WISPER is detectable in the human heart, where it is associated with severe cardiac fibrosis, these data suggest that Wisper could represent a novel therapeutic target for limiting the extent of the fibrotic response in the heart. -- Les long ARN non-codants (IncRNAs) sont des ARN de plus de 200 nucléotides qui ne codent pas pour des protéines. Ils exercent d'importantes fonctions dans le génome. Par contre, leur importance dans le développement de la fibrose cardiaque n'a pas été étudiée. Pour identifier des IncRNAs jouant un rôle dans ce processus, le transcriptome non-codant a été étudié dans le coeur de'souris après un infarctus du myocarde. Nous avons découverts 1500 nouveaux IncRNAs. Ces transcrits ont d'uniques caractéristiques. En particulier ils sont extrêmement spécifiques de sous-populations de cellules cardiaques. Par ailleurs, leur expression est remarquablement corrélée avec les paramètres définissant les dimensions du coeur et la fonction cardiaque. La majorité de ces IncRNAs sont conservés chez l'humain. Certains sont modulés dans des pathologies cardiaques. En utilisant une approche bioinformatique, nous avons identifié un IncRNA qui est associé à des séquences amplificatrices et qui est particulièrement enrichi dans les fibroblastes cardiaques. Ce transcrit a été nommé Wisper pour «Wisp2 super-enhancer-derived IncRNA ». L'importance de Wisper dans la biologie des fibroblastes cardiaques est démontrée dans des expériences de déplétion. En l'absence de Wisper, l'expression de protéines impliquées dans le développement de la fibrose est dramatiquement réduite dans les fibroblastes cardiaques. Ceux-ci montrent une prolifération réduite. Le niveau d'apoptose est largement augmenté. In vivo, la déplétion de Wisper pendant la phase aiguë de l'infarctus rehausse le risque de rupture cardiaque. Au contraire, la réduction de l'expression de Wisper pendant la phase chronique diminue la fibrose cardiaque et améliore la fonction du coeur. Puisque Wisper est exprimé dans le coeur humain, ce transcrit représente une nouvelle cible thérapeutique pour limiter la réponse fibrotique dans le coeur.