The relationship between three anxiety related clusters in projective drawings and anxiety and ego-strength scales of the Minnesota multiphasic personality inventory-2

Based on the shortcomings of past research, the need for understanding and investigation of the general relationship between self-report measures and human figure drawings required understanding and investigation (Riethmiller & Handler, 1997b; Waehler, 1997) while utilising a quantitative, configural scoring approach. Riethmiller and Handler (1997a; 1997b) hypothesised that subjects have one of two typical approach styles to anxiety/stress that influences their execution of the Human Figure Drawing (HFD) Test: “Avoidance” or “Coping” as measured by composite scoring index clusters. They argue that these two approach styles had to be taken into account when investigating anxiety on the HFD Test. According to Handler and Reyher (1965) those who experience more intense anxiety typically rely on an “Avoidant” approach, while those with lower anxiety typically rely on a “Coping” approach. The “Coping” response is hypothesised to suggest good ego-strength, and the “Avoidant” response poor ego-strength. Handler and Reyher (1964; 1965; 1966) also argued that there are two sources of anxiety on projective drawings: internal and external sources of anxiety. They hypothesised that the “External” anxiety cluster (measured by utilising the car drawing) and self-report measures both assess ‘external’ anxiety. Using Handler’s (1967) HFD index scoring manual, this research therefore inve stigated the level of correlation of the two MMPI-2 anxiety scale scores with (a) the hypothesised Stress Approach HFD cluster scores, as well as with (b) the “External” anxiety cluster score, while the hypothesised Stress Approach HFD cluster scores were compared with the (c) MMPI-2 ego strength scale score. The results of the investigated relationships yielded non-significant correlations overall. The differences in nature of the two measurement instruments, and the potential weaknesses of this study, as two likely explanations for these correlations, are discussed. In the consideration of the differences of the two measurement instruments, the weaknesses of SR measures and criterion-related validity are discussed while self- attributed and implicit motives are contrasted with each other. Potential extraneous variables and possible truncated range are discussed as potential weaknesses of this study

Methylation of migraine-related genes in different tissues of the rat

17β-Estradiol, an epigenetic modulator, is involved in the increased prevalence of migraine in women. Together with the prophylactic efficacy of valproate, which influences DNA methylation and histone modification, this points to the involvement of epigenetic mechanisms. Epigenetic studies are often performed on leukocytes, but it is unclear to what extent methylation is similar in other tissues. Therefore, we investigated methylation of migraine-related genes that might be epigenetically regulated (CGRP-ergic pathway, estrogen receptors, endothelial NOS, as well as MTHFR) in different migraine-related tissues and compared this to methylation in rat as well as human leukocytes. Further, we studied whether 17β-estradiol has a prominent role in methylation of these genes. Female rats (n = 35) were ovariectomized or shamoperated and treated with 17b-estradiol or placebo. DNA was isolated and methylation was assessed through bisulphite treatment and mass spectrometry. Human methylation data were obtained using the Illumina 450k genome-wide methylation array in 395 female subjects from a population-based cohort study. We showed that methylation of the Crcp, Calcrl, Esr1 and Nos3 genes is tissue-specific and that methylation in leukocytes was not correlated to that in other tissues. Interestingly, the interindividual variation in methylation differed considerably between genes and tissues. Furthermore we showed that methylation in human leukocytes was similar to that in rat leukocytes in our genes of interest, suggesting that rat may be a good model to study human DNA methylation in tissues that are difficult to obtain. In none of the genes a significant effect of estradiol treatment was observed

Differences between outdoor and indoor sound levels for open, tilted, and closed windows

Noise exposure prediction models for health effect studies normally estimate free field exposure levels outside. However, to assess the noise exposure inside dwellings, an estimate of indoor sound levels is necessary. To date, little field data is available about the difference between indoor and outdoor noise levels and factors affecting the damping of outside noise. This is a major cause of uncertainty in indoor noise exposure prediction and may lead to exposure misclassification in health assessments. This study aims to determine sound level differences between the indoors and the outdoors for different window positions and how this sound damping is related to building characteristics. For this purpose, measurements were carried out at home in a sample of 102 Swiss residents exposed to road traffic noise. Sound pressure level recordings were performed outdoors and indoors, in the living room and in the bedroom. Three scenarios-of open, tilted, and closed windows-were recorded for three minutes each. For each situation, data on additional parameters such as the orientation towards the source, floor, and room, as well as sound insulation characteristics were collected. On that basis, linear regression models were established. The median outdoor-indoor sound level differences were of 10 dB(A) for open, 16 dB(A) for tilted, and 28 dB(A) for closed windows. For open and tilted windows, the most relevant parameters affecting the outdoor-indoor differences were the position of the window, the type and volume of the room, and the age of the building. For closed windows, the relevant parameters were the sound level outside, the material of the window frame, the existence of window gaskets, and the number of windows

Epithelial calcineurin controls microbiota-dependent intestinal tumor development.

Inflammation-associated pathways are active in intestinal epithelial cells (IECs) and contribute to the pathogenesis of colorectal cancer (CRC). Calcineurin, a phosphatase required for the activation of the nuclear factor of activated T cells (NFAT) family of transcription factors, shows increased expression in CRC. We therefore investigated the role of calcineurin in intestinal tumor development. We demonstrate that calcineurin and NFAT factors are constitutively expressed by primary IECs and selectively activated in intestinal tumors as a result of impaired stratification of the tumor-associated microbiota and toll-like receptor signaling. Epithelial calcineurin supports the survival and proliferation of cancer stem cells in an NFAT-dependent manner and promotes the development of intestinal tumors in mice. Moreover, somatic mutations that have been identified in human CRC are associated with constitutive activation of calcineurin, whereas nuclear translocation of NFAT is associated with increased death from CRC. These findings highlight an epithelial cell-intrinsic pathway that integrates signals derived from the commensal microbiota to promote intestinal tumor development.This work was supported by the Deutsche Forschungsgemeinschaft (DFG) grants ZE814/5-1 (S.Z.), BA2863/5-1 (J.F.B.) and CH279/5-1 (T.C.), the European Research Council (ERC) starting grant 336528 (S.Z.), a Postdoctoral Fellowship Award from the Crohn's and Colitis Foundation of America (S.Z.), the European Commission (Marie Curie International Reintegration grant 256363; S.Z.), the DFG Excellence Cluster 'Inflammation at Interfaces' (S.Z. and J.F.B.), the DFG Excellence Cluster 'Center for Regenerative Therapies' (S.Z.); the US National Institutes of Health grants DK044319 (R.S.B.), DK051362 (R.S.B.), DK053056 (R.S.B.) and DK088199 (R.S.B.), the Harvard Digestive Diseases Center (HDDC) grant DK0034854 (R.S.B.), and the AIRC grant IG-14233 (M.E.B.).This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/nm.407

The EffecTs of Amlodipine and other Blood PREssure Lowering Agents on Microvascular FuncTion in Small Vessel Diseases (TREAT-SVDs) trial: Study protocol for a randomised crossover trial

Background: Hypertension is the leading modifiable risk factor for cerebral small vessel diseases (SVDs). Yet, it is unknown whether antihypertensive drug classes differentially affect microvascular function in SVDs. Aims: To test whether amlodipine has a beneficial effect on microvascular function when compared to either losartan or atenolol, and whether losartan has a beneficial effect when compared to atenolol in patients with symptomatic SVDs. Design: TREAT-SVDs is an investigator-led, prospective, open-label, randomised crossover trial with blinded endpoint assessment (PROBE design) conducted at five study sites across Europe. Patients aged 18 years or older with symptomatic SVD who have an indication for antihypertensive treatment and are suffering from either sporadic SVD and a history of lacunar stroke or vascular cognitive impairment (group A) or CADASIL (group B) are randomly allocated 1:1:1 to one of three sequences of antihypertensive treatment. Patients stop their regular antihypertensive medication for a 2-week run-in period followed by 4-week periods of monotherapy with amlodipine, losartan and atenolol in random order as open-label medication in standard dose. Outcomes: The primary outcome measure is cerebrovascular reactivity (CVR) as determined by blood oxygen level dependent brain MRI signal response to hypercapnic challenge with change in CVR in normal appearing white matter as primary endpoint. Secondary outcome measures are mean systolic blood pressure (BP) and BP variability (BPv). Discussion: TREAT-SVDs will provide insights into the effects of different antihypertensive drugs on CVR, BP, and BPv in patients with symptomatic sporadic and hereditary SVDs. Funding: European Union's Horizon 2020 programme

Preoperative Brain Tumor Imaging: Models and Software for Segmentation and Standardized Reporting

For patients suffering from brain tumor, prognosis estimation and treatment decisions are made by a multidisciplinary team based on a set of preoperative MR scans. Currently, the lack of standardized and automatic methods for tumor detection and generation of clinical reports, incorporating a wide range of tumor characteristics, represents a major hurdle. In this study, we investigate the most occurring brain tumor types: glioblastomas, lower grade gliomas, meningiomas, and metastases, through four cohorts of up to 4,000 patients. Tumor segmentation models were trained using the AGU-Net architecture with different preprocessing steps and protocols. Segmentation performances were assessed in-depth using a wide-range of voxel and patient-wise metrics covering volume, distance, and probabilistic aspects. Finally, two software solutions have been developed, enabling an easy use of the trained models and standardized generation of clinical reports: Raidionics and Raidionics-Slicer. Segmentation performances were quite homogeneous across the four different brain tumor types, with an average true positive Dice ranging between 80 and 90%, patient-wise recall between 88 and 98%, and patient-wise precision around 95%. In conjunction to Dice, the identified most relevant other metrics were the relative absolute volume difference, the variation of information, and the Hausdorff, Mahalanobis, and object average symmetric surface distances. With our Raidionics software, running on a desktop computer with CPU support, tumor segmentation can be performed in 16–54 s depending on the dimensions of the MRI volume. For the generation of a standardized clinical report, including the tumor segmentation and features computation, 5–15 min are necessary. All trained models have been made open-access together with the source code for both software solutions and validation metrics computation. In the future, a method to convert results from a set of metrics into a final single score would be highly desirable for easier ranking across trained models. In addition, an automatic classification of the brain tumor type would be necessary to replace manual user input. Finally, the inclusion of post-operative segmentation in both software solutions will be key for generating complete post-operative standardized clinical reports.publishedVersio

Common genetic determinants of intraocular pressure and primary open-angle Glaucoma

10.1371/journal.pgen.1002611PLoS Genetics85

The ERCC6 Gene and Age-Related Macular Degeneration

Background: Age-related macular degeneration (AMD) is the leading cause of irreversible visual loss in the developed countries and is caused by both environmental and genetic factors. A recent study (Tuo et al., PNAS) reported an association between AMD and a single nucleotide polymorphism (SNP) (rs3793784) in the ERCC6 (NM_000124) gene. The risk allele also increased ERCC6 expression. ERCC6 is involved in DNA repair and mutations in ERCC6 cause Cockayne syndrome (CS). Amongst others, photosensitivity and pigmentary retinopathy are hallmarks of CS. Methodology/Principal Findings: Separate and combined data from three large AMD case-control studies and a prospective population-based study (The Rotterdam Study) were used to analyse the genetic association between ERCC6 and AMD (2682 AMD cases and 3152 controls). We also measured ERCC6 mRNA levels in retinal pigment epithelium (RPE) cells of healthy and early AMD affected human donor eyes. Rs3793784 conferred a small increase in risk for late AMD in the Dutch population (The Rotterdam and AMRO-NL study), but this was not replicated in two non-European studies (AREDS, Columbia University). In addition, the AMRO-NL study revealed no significant association for 9 other variants spanning ERCC6. Finally, we determined that ERCC6 expression in the human RPE did not depend on rs3793784 genotype, but, interestingly, on AMD status: Early AMD-affected donor eyes had a 50% lower ERCC6 expression than healthy donor eyes (P = 0.018). Conclusions/Significance: Our meta analysis of four Caucasian cohorts does not replicate the reported association between SNPs in ERCC6 and AMD. Nevertheless, our findings on ERCC6 expression in the RPE suggest that ERCC6 may be functionally involved in AMD. Combining our data with those of the literature, we hypothesize that the AMD-related reduced transcriptional activity of ERCC6 may be caused by diverse, small and heterogeneous genetic and/or environmental determinants

Utilising phytanic acid diastereomers for the characterisation of archaeological lipid residues in pottery samples

Phytanic acid diastereomers, 3S,7R,11R,15-phytanic acid (SRR) and 3R,7R,11R,15-phytanic acid (RRR), were determined by GC-MS in extracts of archaeological ceramic. The SRR% was higher in pottery from coastal sites corresponding with 13C enriched n-alkanoic acid corroborating a predominantly marine origin for the food residues. Conversely, low SRR% and 13C depleted n-alkanoic acid were found at inland sites, which are most likely derived from ruminant products. These observations are explained by differences in the bacterial transformation of phytol to phytanic acid between ruminant and aquatic organisms and allow these products to be easily distinguished in archaeological contexts