Electron-multiplying CCDs for future soft X-ray spectrometers

CCDs have been used in several high resolution soft X-ray spectrometers for both space and terrestrial applications such as the Reflection Grating Spectrometer on XMM-Newton and the Super Advanced X-ray Emission Spectrometer at the Paul Scherrer Institut in Switzerland. However, with their ability to use multiplication gain to amplify signal and suppress readout noise, EM-CCDs are being considered instead of CCDs for future soft X-ray spectrometers. When detecting low energy X-rays, EM-CCDs are able to increase the Signal-to-Noise ratio of the device, making the X-rays much easier to detect. If the signal is also significantly split between neighbouring pixels, the increase in the size of the signal will make complete charge collection and techniques such as centroiding easier to accomplish. However, multiplication gain from an EM-CCD does cause a degradation of the energy resolution of the device and there are questions about how the high field region in an EM-CCD will behave over time in high radiation environments. This paper analyses the possible advantages and disadvantages of using EM-CCDs for high resolution soft X-ray spectroscopy and suggests in which situations using them would not only be possible, but also beneficial to the instrument

A data-driven model of brain volume changes in progressive supranuclear palsy

Supplementary material: Supplementary material is available at Brain Communications online.Copyright © The Author(s) 2022. The most common clinical phenotype of progressive supranuclear palsy is Richardson syndrome, characterized by levodopa unresponsive symmetric parkinsonism, with a vertical supranuclear gaze palsy, early falls and cognitive impairment. There is currently no detailed understanding of the full sequence of disease pathophysiology in progressive supranuclear palsy. Determining the sequence of brain atrophy in progressive supranuclear palsy could provide important insights into the mechanisms of disease progression, as well as guide patient stratification and monitoring for clinical trials. We used a probabilistic event-based model applied to cross-sectional structural MRI scans in a large international cohort, to determine the sequence of brain atrophy in clinically diagnosed progressive supranuclear palsy Richardson syndrome. A total of 341 people with Richardson syndrome (of whom 255 had 12-month follow-up imaging) and 260 controls were included in the study. We used a combination of 12-month follow-up MRI scans, and a validated clinical rating score (progressive supranuclear palsy rating scale) to demonstrate the longitudinal consistency and utility of the event-based model’s staging system. The event-based model estimated that the earliest atrophy occurs in the brainstem and subcortical regions followed by progression caudally into the superior cerebellar peduncle and deep cerebellar nuclei, and rostrally to the cortex. The sequence of cortical atrophy progresses in an anterior to posterior direction, beginning in the insula and then the frontal lobe before spreading to the temporal, parietal and finally the occipital lobe. This in vivo ordering accords with the post-mortem neuropathological staging of progressive supranuclear palsy and was robust under cross-validation. Using longitudinal information from 12-month follow-up scans, we demonstrate that subjects consistently move to later stages over this time interval, supporting the validity of the model. In addition, both clinical severity (progressive supranuclear palsy rating scale) and disease duration were significantly correlated with the predicted subject event-based model stage (P < 0.01). Our results provide new insights into the sequence of atrophy progression in progressive supranuclear palsy and offer potential utility to stratify people with this disease on entry into clinical trials based on disease stage, as well as track disease progression.We thank the research participants for their contribution to the study. The Dementia Research Centre is supported by Alzheimer’s Research UK, Alzheimer’s Society, Brain Research UK and The Wolfson Foundation. This work was supported by the National Institute of Health Research UCLH Biomedical Research Centre, the Leonard Wolfson Experimental Neurology Centre Clinical Research Facility and the UK Dementia Research Institute (DRI), which receives its funding from UK DRI Ltd, funded by the UK Medical Research Council, Alzheimer’s Society and Alzheimer’s Research UK. The Progressive Supranuclear Palsy-Cortico-Basal Syndrome-Multiple System Atrophy (PROSPECT) study is funded by the PSP Association and CBD Solutions. The 4-repeat tauopathy neuroimaging initiative (4RTNI) and frontotemporal lobar degeneration neuroimaging initiative (FTLDNI) are funded by the National Institutes of Health Grant R01 AG038791 and through generous contributions from the Tau Research Consortium. Both are coordinated through the University of California, San Francisco, Memory and Aging Center. 4RTNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. W.J.S. is supported by a Wellcome Trust Clinical PhD fellowship (220582/Z/20/Z). M.B. is supported by a Fellowship award from the Alzheimer’s Society, UK (AS-JF-19a-004-517) and the UK Dementia Research Institute. N.P.O. is a UK Research and Innovation Future Leaders Fellow (MR/S03546X/1). D.C.A. is supported by the Engineering and Physical Sciences Research Council (EP/M020533/1); Medical Research Council (MR/T046422/1); Wellcome Trust (UNS113739). D.M.C. is supported by the UK Dementia Research Institute, as well as Alzheimer’s Research UK (ARUK-PG2017-1946) and the UCL/UCLH National Institute of Health Research Biomedical Research Centre. H.R.M. is supported by Parkinson’s UK, Cure Parkinson’s Trust, PSP Association, CBD Solutions, Drake Foundation, Medical Research Council, and the Michael J Fox Foundation. H.H. is supported by the National Institute of Health (R01AG038791, U19AG063911). L.V.V. is supported by National Institute of Health (R01AG038791). J.B.R. is supported by the Wellcome Trust (220258); National Institute of Health Research Cambridge Biomedical Research Centre (BRC-1215-20014); PSP Association; Evelyn Trust; Medical Research Council (SUAG051 R101400). A.B. is supported by National Institute of U19AG063911, R01AG038791, R01AG073482, U24AG057437, the Rainwater Charitable Foundation, the Bluefield Project to Cure FTD, the Alzheimer’s Association and the Association for Frontotemporal Degeneration. J.D.R. is supported by the Miriam Marks Brain Research UK Senior Fellowship and has received funding from a Medical Research Council Clinician Scientist Fellowship (MR/M008525/1) and the National Institute of Health Research Rare Disease Translational Research Collaboration (BRC149/NS/MH). P.A.W. is supported by a Medical Research Council Skills Development Fellowship (MR/T027770/1)

The transmission spectrum of Earth through lunar eclipse observations

Of the 342 planets discovered so far orbiting other stars, 58 "transit" the stellar disk, meaning that they can be detected by a periodic decrease in the starlight flux. The light from the star passes through the atmosphere of the planet, and in a few cases the basic atmospheric composition of the planet can be estimated. As we get closer to finding analogues of Earth, an important consideration toward the characterization of exoplanetary atmospheres is what the transmission spectrum of our planet looks like. Here we report the optical and near-infrared transmission spectrum of the Earth, obtained during a lunar eclipse. Some biologically relevant atmospheric features that are weak in the reflected spectrum (such as ozone, molecular oxygen, water, carbon dioxide and methane) are much stronger in the transmission spectrum, and indeed stronger than predicted by modelling. We also find the fingerprints of the Earth's ionosphere and of the major atmospheric constituent, diatomic nitrogen (N2), which are missing in the reflected spectrum.Comment: Published in Nature, 11 July 2009. This file also contains the on-line materia

The Open-Access European Prevention of Alzheimer's Dementia (EPAD) MRI dataset and processing workflow

The European Prevention of Alzheimer Dementia (EPAD) is a multi-center study that aims to characterize the preclinical and prodromal stages of Alzheimer's Disease. The EPAD imaging dataset includes core (3D T1w, 3D FLAIR) and advanced (ASL, diffusion MRI, and resting-state fMRI) MRI sequences. Here, we give an overview of the semi-automatic multimodal and multisite pipeline that we developed to curate, preprocess, quality control (QC), and compute image-derived phenotypes (IDPs) from the EPAD MRI dataset. This pipeline harmonizes DICOM data structure across sites and performs standardized MRI preprocessing steps. A semi-automated MRI QC procedure was implemented to visualize and flag MRI images next to site-specific distributions of QC features - i.e. metrics that represent image quality. The value of each of these QC features was evaluated through comparison with visual assessment and step-wise parameter selection based on logistic regression. IDPs were computed from 5 different MRI modalities and their sanity and potential clinical relevance were ascertained by assessing their relationship with biological markers of aging and dementia. The EPAD v1500.0 data release encompassed core structural scans from 1356 participants 842 fMRI, 831 dMRI, and 858 ASL scans. From 1356 3D T1w images, we identified 17 images with poor quality and 61 with moderate quality. Five QC features - Signal to Noise Ratio (SNR), Contrast to Noise Ratio (CNR), Coefficient of Joint Variation (CJV), Foreground-Background energy Ratio (FBER), and Image Quality Rate (IQR) - were selected as the most informative on image quality by comparison with visual assessment. The multimodal IDPs showed greater impairment in associations with age and dementia biomarkers, demonstrating the potential of the dataset for future clinical analyses

Assessing weight perception accuracy to promote weight loss among U.S. female adolescents: A secondary analysis

<p>Abstract</p> <p>Background</p> <p>Overweight and obesity have become a global epidemic. The prevalence of overweight and obesity among U.S. adolescents has almost tripled in the last 30 years. Results from recent systematic reviews demonstrate that no single, particular intervention or strategy successfully assists overweight or obese adolescents in losing weight. An understanding of factors that influence healthy weight-loss behaviors among overweight and obese female adolescents promotes effective, multi-component weight-loss interventions. There is limited evidence demonstrating associations between demographic variables, body-mass index, and weight perception among female adolescents trying to lose weight. There is also a lack of previous studies examining the association of the accuracy of female adolescents' weight perception with their efforts to lose weight. This study, therefore, examined the associations of body-mass index, weight perception, and weight-perception accuracy with trying to lose weight and engaging in exercise as a weight-loss method among a representative sample of U.S. female adolescents.</p> <p>Methods</p> <p>A nonexperimental, descriptive, comparative secondary analysis design was conducted using data from Wave II (1996) of the National Longitudinal Study of Adolescent Health (Add Health). Data representative of U.S. female adolescents (N = 2216) were analyzed using STATA statistical software. Descriptive statistics and survey weight logistic regression were performed to determine if demographic and independent (body-mass index, weight perception, and weight perception accuracy) variables were associated with trying to lose weight and engaging in exercise as a weight-loss method.</p> <p>Results</p> <p>Age, Black or African American race, body-mass index, weight perception, and weight perceptions accuracy were consistently associated with the likeliness of trying to lose weight among U.S. female adolescents. Age, body-mass index, weight perception, and weight-perception accuracy were positively associated (<it>p </it>< 0.05) with trying to lose weight. Black/African American subjects were significantly less likely than their White counterparts to be trying to lose weight. There was no association between demographic or independent variables and engaging in exercise as a weight-loss method.</p> <p>Conclusions</p> <p>Findings suggest that factors influencing weight-loss efforts, including age, race, body-mass index, weight perception, and weight-perception accuracy, should be incorporated into existing or new multi-component weight-loss interventions for U.S. adolescent females in order to help reduce the national epidemic of overweight and obesity among U.S. female adolescents.</p

Global DNA Hypomethylation in Peripheral Blood Leukocytes as a Biomarker for Cancer Risk: A Meta-Analysis

BACKGROUND: Good biomarkers for early detection of cancer lead to better prognosis. However, harvesting tumor tissue is invasive and cannot be routinely performed. Global DNA methylation of peripheral blood leukocyte DNA was evaluated as a biomarker for cancer risk. METHODS: We performed a meta-analysis to estimate overall cancer risk according to global DNA hypomethylation levels among studies with various cancer types and analytical methods used to measure DNA methylation. Studies were systemically searched via PubMed with no language limitation up to July 2011. Summary estimates were calculated using a fixed effects model. RESULTS: The subgroup analyses by experimental methods to determine DNA methylation level were performed due to heterogeneity within the selected studies (p<0.001, I(2): 80%). Heterogeneity was not found in the subgroup of %5-mC (p = 0.393, I(2): 0%) and LINE-1 used same target sequence (p = 0.097, I(2): 49%), whereas considerable variance remained in LINE-1 (p<0.001, I(2): 80%) and bladder cancer studies (p = 0.016, I(2): 76%). These results suggest that experimental methods used to quantify global DNA methylation levels are important factors in the association study between hypomethylation levels and cancer risk. Overall, cancer risks of the group with the lowest DNA methylation levels were significantly higher compared to the group with the highest methylation levels [OR (95% CI): 1.48 (1.28-1.70)]. CONCLUSIONS: Global DNA hypomethylation in peripheral blood leukocytes may be a suitable biomarker for cancer risk. However, the association between global DNA methylation and cancer risk may be different based on experimental methods, and region of DNA targeted for measuring global hypomethylation levels as well as the cancer type. Therefore, it is important to select a precise and accurate surrogate marker for global DNA methylation levels in the association studies between global DNA methylation levels in peripheral leukocyte and cancer risk

Characterization of K-Complexes and Slow Wave Activity in a Neural Mass Model

NREM sleep is characterized by two hallmarks, namely K-complexes (KCs) during sleep stage N2 and cortical slow oscillations (SOs) during sleep stage N3. While the underlying dynamics on the neuronal level is well known and can be easily measured, the resulting behavior on the macroscopic population level remains unclear. On the basis of an extended neural mass model of the cortex, we suggest a new interpretation of the mechanisms responsible for the generation of KCs and SOs. As the cortex transitions from wake to deep sleep, in our model it approaches an oscillatory regime via a Hopf bifurcation. Importantly, there is a canard phenomenon arising from a homoclinic bifurcation, whose orbit determines the shape of large amplitude SOs. A KC corresponds to a single excursion along the homoclinic orbit, while SOs are noise-driven oscillations around a stable focus. The model generates both time series and spectra that strikingly resemble real electroencephalogram data and points out possible differences between the different stages of natural sleep

A Systematic Review of the Effectiveness of Acceptance and Commitment Therapy (ACT) for Body Image Dissatisfaction and Weight Self-Stigma in Adults

© 2018, The Author(s). Body image dissatisfaction (BID) and weight self-stigma are prevalent and associated with physical and psychological ill-health. Acceptance and Commitment Therapy (ACT) is increasingly employed for both, yet little is known about its effectiveness. Searches of 12 databases identified six studies using online, face-to-face or self-help ACT interventions for BID or weight self-stigma, of varying duration and intensity. Their effectiveness and quality were evaluated. Two reported improved BID, three improved weight self-stigma, and one reported no impact on weight self-stigma. Methodological issues (small sample sizes, lack of allocation concealment, attention control and long-term follow up) impacted the validity of findings. Due to the small number of studies and poor study quality, the effectiveness of ACT for BID and weight self-stigma remains unclear. Nonetheless findings suggest psychological flexibility may facilitate reduction in BID and weight self-stigma and indicate that brief online as well as lengthy face-to-face delivery may be useful. Suggestions for further research are made

A Unique Regulator Contributes to Quorum Sensing and Virulence in Burkholderia cenocepacia

Burkholderia cenocepacia causes chronic and life-threatening respiratory infections in immunocompromized people. The B. cenocepacia N-acyl-homoserine lactone (AHL)-dependent quorum sensing system relies on the production of AHLs by the synthases CepI and CciI while CepR, CciR and CepR2 control expression of many genes important for pathogenesis. Downstream from, and co-transcribed with cepI, lies BCAM1871 encoding a hypothetical protein that was uncharacterized prior to this study. Orthologs of B. cenocepacia BCAM1871 are uniquely found in Burkholderia spp and are conserved in their genomic locations in pathogenic Burkholderia. We observed significant effects on AHL activity upon mutation or overexpression of BCAM1871, although these effects were more subtle than those observed for CepI indicating BCAM1871 acts as an enhancer of AHL activity. Transcription of cepI, cepR and cciIR was significantly reduced in the BCAM1871 mutant. Swimming and swarming motilities as well as transcription of fliC, encoding flagellin, were significantly reduced in the BCAM1871 mutant. Protease activity and transcription of zmpA and zmpB, encoding extracellular zinc metalloproteases, were undetectable in the BCAM1871 mutant indicating a more significant effect of mutating BCAM1871 than cepI. Exogenous addition of OHL restored cepI, cepR and fliC transcription but had no effect on motility, protease activity or zmpA or zmpB transcription suggesting AHL-independent effects. The BCAM1871 mutant exhibited significantly reduced virulence in rat chronic respiratory and nematode infection models. Gene expression and phenotypic assays as well as vertebrate and invertebrate infection models showed that BCAM1871 significantly contributes to pathogenesis in B. cenocepacia