Inter-reader agreement of the PI-QUAL score for prostate MRI quality in the NeuroSAFE PROOF trial

Objectives: The Prostate Imaging Quality (PI-QUAL) score assesses the quality of multiparametric MRI (mpMRI). A score of 1 means all sequences are below the minimum standard of diagnostic quality, 3 implies that the scan is of sufficient diagnostic quality, and 5 means that all three sequences are of optimal diagnostic quality. We investigated the inter-reader reproducibility of the PI-QUAL score in patients enrolled in the NeuroSAFE PROOF trial. Methods: We analysed the scans of 103 patients on different MR systems and vendors from 12 different hospitals. Two dedicated radiologists highly experienced in prostate mpMRI independently assessed the PI-QUAL score for each scan. Interobserver agreement was assessed using Cohen’s kappa with standard quadratic weighting (κw) and percent agreement. Results: The agreement for each single PI-QUAL score was strong (κw = 0.85 and percent agreement = 84%). A similar agreement (κw = 0.82 and percent agreement = 84%) was observed when the scans were clustered into three groups (PI-QUAL 1–2 vs PI-QUAL 3 vs PI-QUAL 4–5). The agreement in terms of diagnostic quality for each single sequence was highest for T2-weighted imaging (92/103 scans; 89%), followed by dynamic contrast-enhanced sequences (91/103; 88%) and diffusion-weighted imaging (80/103; 78%). Conclusion: We observed strong reproducibility in the assessment of PI-QUAL between two radiologists with high expertise in prostate mpMRI. At present, PI-QUAL offers clinicians the only available tool for evaluating and reporting the quality of prostate mpMRI in a systematic manner but further refinements of this scoring system are warranted

Mutation of Directed Graphs -- Corresponding Regular Expressions and Complexity of Their Generation

Directed graphs (DG), interpreted as state transition diagrams, are traditionally used to represent finite-state automata (FSA). In the context of formal languages, both FSA and regular expressions (RE) are equivalent in that they accept and generate, respectively, type-3 (regular) languages. Based on our previous work, this paper analyzes effects of graph manipulations on corresponding RE. In this present, starting stage we assume that the DG under consideration contains no cycles. Graph manipulation is performed by deleting or inserting of nodes or arcs. Combined and/or multiple application of these basic operators enable a great variety of transformations of DG (and corresponding RE) that can be seen as mutants of the original DG (and corresponding RE). DG are popular for modeling complex systems; however they easily become intractable if the system under consideration is complex and/or large. In such situations, we propose to switch to corresponding RE in order to benefit from their compact format for modeling and algebraic operations for analysis. The results of the study are of great potential interest to mutation testing

ASOHF: a new adaptive spherical overdensity halo finder

We present and test a new halo finder based on the spherical overdensity (SO) method. This new adaptive spherical overdensity halo finder (ASOHF) is able to identify dark matter haloes and their substructures (subhaloes) down to the scales allowed by the analysed simulations. The code has been especially designed for the adaptive mesh refinement cosmological codes, although it can be used as a stand-alone halo finder for N-body codes. It has been optimised for the purpose of building the merger tree of the haloes. In order to verify the viability of this new tool, we have developed a set of bed tests that allows us to estimate the performance of the finder. Finally, we apply the halo finder to a cosmological simulation and compare the results obtained to those given by other well known publicly available halo finders.Comment: Latex format, 16 pages, 11 postscript figures, accepted for publication in Astronomy and Astrophysic

Experiences of Interventions Aiming to Improve the Mental Health and Wellbeing of Children and Young People with a Long-Term Physical Condition: A Systematic Review and Meta-ethnography

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this recordBackground Children and young people with long term physical health conditions are at increased risk of experiencing mental health and wellbeing difficulties. However, there is a lack of research that explores the experiences of, and attitudes towards interventions aiming to improve their mental health and wellbeing. This systematic review seeks to address this gap in the literature by exploring what children and young people with long term conditions, their caregivers and health practitioners perceive to be important aspects of interventions aiming to improve their mental health and wellbeing. Methods An information specialist searched five academic databases using pre‐defined criteria for qualitative evaluations of interventions aiming to improve the mental health or wellbeing of children with long term physical conditions. Reviewers also performed supplementary citation and grey literature searches. Two reviewers independently screened titles, abstracts and full texts which met the inclusion criteria and conducted data extraction and quality assessment. Meta‐ethnography was used to synthesise the findings. Results Screening identified 60 relevant articles. We identified five overarching constructs through the synthesis: i) Getting In and Staying In, ii) Therapeutic Foundation, iii) Social Support, iv) A Hopeful Alternative and v) Empowerment. The line of argument which links these constructs together indicates that when interventions can provide an environment that allows young people to share their experiences and build empathetic relationships; it can enable participants to access social support and increase feelings of hope and empowerment. Conclusion These findings may provide a framework to inform the development of mental health interventions for this population, and evaluate existing interventions which already include some of the components or processes identified by this research. Further research is needed to establish which of the constructs identified by the line of argument are most effective in improving the mental wellbeing of young people living with long term conditions.National Institute for Health Research (NIHR

Domain-wall motion and interfacial Dzyaloshinskii-Moriya interactions in Pt/Co/Ir(tIr)/Ta multilayers

The interfacial Dzyaloshinskii-Moriya interaction (DMI) is important for chiral domain walls (DWs) and for stabilizing magnetic skyrmions. We study the effects of introducing increasing thicknesses of Ir, from zero to 2 nm, into a Pt/Co/Ta multilayer between the Co and Ta layers. There is a marked increase in magnetic moment, due to the suppression of the dead layer at the interface with Ta, but the perpendicular anisotropy is hardly affected. All samples show a universal scaling of the field-driven DW velocity across the creep and depinning regimes. Asymmetric bubble expansion shows that DWs in all of the samples have the left-handed Néel form. The value of in-plane magnetic field at which the creep velocity shows a minimum drops markedly on the introduction of Ir, as does the frequency shift of the Stokes and anti-Stokes peaks in Brillouin light scattering (BLS) measurements. Despite this qualitative similarity, there are quantitative differences in the DMI strength given by the two measurements, with BLS often returning higher values. Many features in bubble expansion velocity curves do not fit simple models commonly used, namely a lack of symmetry about the velocity minimum and no difference in velocities at high in-plane fields. These features are explained by the use of a new model in which the depinning field is allowed to vary with in-plane field in a way determined from micromagnetic simulations. This theory shows that the velocity minimum underestimates the DMI field, consistent with BLS giving higher values. Our results suggest that the DMI at an Ir/Co interface has the same sign as the DMI at a Pt/Co interface

The effects of a hot gaseous halo on disc thickening in galaxy minor mergers

We employ hydrodynamical simulations to study the effects of dissipational gas physics on the vertical heating and thickening of disc galaxies during minor mergers. For the first time we present a suite of simulations that includes a diffuse, rotating, cooling, hot gaseous halo, as predicted by cosmological hydrodynamical simulations as well as models of galaxy formation. We study the effect of this new gaseous component on the vertical structure of a Milky Way-like stellar disc during 1:10 and 1:5 mergers. For 1:10 mergers we find no increased final thin disc scale height compared to the isolated simulation, leading to the conclusion that thin discs can be present even after a 1:10 merger if a reasonable amount of hot gas is present. The reason for this is the accretion of new cold gas, leading to the formation of a massive new thin stellar disc that dominates the surface brightness profile. In a previous study, in which we included only cold gas in the disk, we showed that the presence of cold gas decreased the thickening by a minor merger relative to the no-gas case. Here, we show that the evolution of the scale height in the presences of a cooling hot halo is dominated by the formation of the new stellar disc. In this scenario, the thick disc is the old stellar disc that has been thickened in a minor merger at z>1, while the thin disc is the new stellar disc that reforms after this merger. In addition, we study the evolution of the scale height during a 1:5 merger and find that a thin disc can be present even after this merger, provided enough hot gas is available. The final scale height in our simulations depends on the mass of the hot gaseous halo, the efficiency of the winds and the merger mass ratio. We find post-merger values in the range 0.5<z0<1.0 kpc in good agreement with observational constraints by local galaxies.Comment: 14 pages, 10 figures, 2 tables, submitted to MNRA

A quantitative explanation of the observed population of Milky Way satellite galaxies

We revisit the well known discrepancy between the observed number of Milky Way (MW) dwarf satellite companions and the predicted population of cold dark matter (CDM) sub-halos, in light of the dozen new low luminosity satellites found in SDSS imaging data and our recent calibration of the SDSS satellite detection efficiency, which implies a total population far larger than these dozen discoveries. We combine a dynamical model for the CDM sub-halo population with simple, physically motivated prescriptions for assigning stellar content to each sub-halo, then apply observational selection effects and compare to the current observational census. As expected, models in which the stellar mass is a constant fraction F(Omega_b/Omega_m) of the sub-halo mass M_sat at the time it becomes a satellite fail for any choice of F. However, previously advocated models that invoke suppression of gas accretion after reionization in halos with circular velocity v_c <~ 35 km/s can reproduce the observed satellite counts for -15 < M_V < 0, with F ~ 10^{-3}. Successful models also require strong suppression of star formation BEFORE reionization in halos with v_c <~ 10 km/s; models without pre-reionization suppression predict far too many satellites with -5 < M_V < 0. Our models also reproduce the observed stellar velocity dispersions ~ 5-10 km/s of the SDSS dwarfs given the observed sizes of their stellar distributions, and model satellites have M(<300 pc) ~ 10^7 M_sun as observed even though their present day total halo masses span more than two orders of magnitude. Our modeling shows that natural physical mechanisms acting within the CDM framework can quantitatively explain the properties of the MW satellite population as it is presently known, thus providing a convincing solution to the `missing satellite' problem.Comment: 18 pages, 14 figures, accepted to ApJ. Minor changes following referees repor

Latent cluster analysis of ALS phenotypes identifies prognostically differing groups

BACKGROUND Amyotrophic lateral sclerosis (ALS) is a degenerative disease predominantly affecting motor neurons and manifesting as several different phenotypes. Whether these phenotypes correspond to different underlying disease processes is unknown. We used latent cluster analysis to identify groupings of clinical variables in an objective and unbiased way to improve phenotyping for clinical and research purposes. METHODS Latent class cluster analysis was applied to a large database consisting of 1467 records of people with ALS, using discrete variables which can be readily determined at the first clinic appointment. The model was tested for clinical relevance by survival analysis of the phenotypic groupings using the Kaplan-Meier method. RESULTS The best model generated five distinct phenotypic classes that strongly predicted survival (p<0.0001). Eight variables were used for the latent class analysis, but a good estimate of the classification could be obtained using just two variables: site of first symptoms (bulbar or limb) and time from symptom onset to diagnosis (p<0.00001). CONCLUSION The five phenotypic classes identified using latent cluster analysis can predict prognosis. They could be used to stratify patients recruited into clinical trials and generating more homogeneous disease groups for genetic, proteomic and risk factor research

Downregulation of MicroRNA-9 in iPSC-Derived Neurons of FTD/ALS Patients with TDP-43 Mutations

Transactive response DNA-binding protein 43 (TDP-43) is a major pathological protein in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). There are many disease-associated mutations in TDP-43, and several cellular and animal models with ectopic overexpression of mutant TDP-43 have been established. Here we sought to study altered molecular events in FTD and ALS by using induced pluripotent stem cell (iPSC) derived patient neurons. We generated multiple iPSC lines from an FTD/ALS patient with the TARDBP A90V mutation and from an unaffected family member who lacked the mutation. After extensive characterization, two to three iPSC lines from each subject were selected, differentiated into postmitotic neurons, and screened for relevant cell-autonomous phenotypes. Patient-derived neurons were more sensitive than control neurons to 100 nM straurosporine but not to other inducers of cellular stress. Three disease-relevant cellular phenotypes were revealed under staurosporine-induced stress. First, TDP-43 was localized in the cytoplasm of a higher percentage of patient neurons than control neurons. Second, the total TDP-43 level was lower in patient neurons with the A90V mutation. Third, the levels of microRNA-9 (miR-9) and its precursor pri-miR-9-2 decreased in patient neurons but not in control neurons. The latter is likely because of reduced TDP-43, as shRNA-mediated TDP-43 knockdown in rodent primary neurons also decreased the pri-miR-9-2 level. The reduction in miR-9 expression was confirmed in human neurons derived from iPSC lines containing the more pathogenic TARDBP M337V mutation, suggesting miR-9 downregulation might be a common pathogenic event in FTD/ALS. These results show that iPSC models of FTD/ALS are useful for revealing stress-dependent cellular defects of human patient neurons containing rare TDP-43 mutations in their native genetic contexts

Results from the Mars Phoenix Lander Robotic Arm experiment

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95618/1/jgre2693.pd