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The Man Who Mistook His Neuropsychologist For a Popstar: When Configural Processing Fails in Acquired Prosopagnosia
We report the case of an individual with acquired prosopagnosia who experiences extreme difficulties in recognizing familiar faces in everyday life despite excellent object recognition skills. Formal testing indicates that he is also severely impaired at remembering pre-experimentally unfamiliar faces and that he takes an extremely long time to identify famous faces and to match unfamiliar faces. Nevertheless, he performs as accurately and quickly as controls at identifying inverted familiar and unfamiliar faces and can recognize famous faces from their external features. He also performs as accurately as controls at recognizing famous faces when fracturing conceals the configural information in the face. He shows evidence of impaired global processing but normal local processing of Navon figures. This case appears to reflect the clearest example yet of an acquired prosopagnosic patient whose familiar face recognition deficit is caused by a severe configural processing deficit in the absence of any problems in featural processing. These preserved featural skills together with apparently intact visual imagery for faces allow him to identify a surprisingly large number of famous faces when unlimited time is available. The theoretical implications of this pattern of performance for understanding the nature of acquired prosopagnosia are discussed.DY, Avery Braun, Jacob Waite, and Nadine Wanke, Bruno Rossion, Thomas Busigny and the grant awarded by AJ by the Experimental Psychology Society (EPS
Intrarenal Resistance Index as a Prognostic Parameter in Patients with Liver Cirrhosis Compared with Other Hepatic Scoring Systems
Background and Aims: Patients with advanced liver cirrhosis who develop renal dysfunction have a poor prognosis. Elevated intrarenal resistance indices (RIs) due to renal vascular constriction have been described before in cirrhotic patients. In the current study, we prospectively investigated the course of intrarenal RIs and compared their prognostic impact with those of the Model for End-Stage Liver Disease (MELD) and the Child-Pugh scores. Methods: Sixty-three patients with liver cirrhosis underwent a baseline visit which included a sonographic examination and laboratory tests. Forty-four patients were prospectively monitored. The end points were death or survival at the day of the follow-up visit. Results: In 28 patients, a follow-up visit was performed after 22 8 months (group 1). Sixteen patients died during follow-up after 12 8 months (group 2). Group 2 patients showed a significantly higher baseline RI (0.76 +/- 0.05) than group 1 patients (RI = 0.72 +/- 0.06; p < 0.05). As shown by receiver operating characteristic analysis, the RI and the MELD score achieved similar sensitivity and specificity {[}area under the curve (AUC): 0.722; 95% confidence interval (95% CI): 0.575-0.873 vs. AUC: 0.724; 95% CI: 0.575-0.873, z = 0.029, n.s.] in predicting survival and were superior to the Child-Pugh score (AUC: 0.677; 96% Cl: 0.518-0.837). Conclusion: The RI is not inferior in sensitivity and specificity to the MELD score. Cirrhotic patients with elevated RIs have impaired short- and long-term survival. The RI may help identify high-risk patients that require special therapeutic care. Copyright (C) 2012 S. Karger AG, Base
Particle Impact Analysis of Bulk Powder During Pneumatic Conveyance
Fragmentation of powders during transportation is a common problem for manufacturers of food and pharmaceutical products. We illustrate that the primary cause of breakage is due to inter-particle collisions, rather than particle-wall impacts, and provide a statistical mechanics model giving the number of collisions resulting in fragmentation
The Multi-Fungicide Resistance Status of Aspergillus fumigatus Populations in Arable Soils and the Wider European Environment
The evolution and spread of pan-azole resistance alleles in clinical and environmental isolates of Aspergillus fumigatus is a global human health concern. The identification of hotspots for azole resistance development in the wider environment can inform optimal measures to counteract further spread by minimizing exposure to azole fungicides and reducing inoculum build-up and pathogen dispersal. We investigated the fungicide sensitivity status of soil populations sampled from arable crops and the wider environment and compared these with urban airborne populations. Low levels of azole resistance were observed for isolates carrying the CYP51A variant F46Y/M172V/E427K, all belonging to a cluster of related cell surface protein (CSP) types which included t07, t08, t13, t15, t19, and t02B, a new allele. High levels of resistance were found in soil isolates carrying CYP51A variants TR34/L98H and TR46/Y121F/T289A, all belonging to CSP types t01, t02, t04B, or t11. TR46/Y121F/M172V/T289A/G448S (CSP t01) and TR46/Y121F/T289A/S363P/I364V/G448S (CSP t01), a new haplotype associated with high levels of resistance, were isolated from Dutch urban air samples, indicating azole resistance evolution is ongoing. Based on low numbers of pan-azole resistant isolates and lack of new genotypes in soils of fungicide-treated commercial and experimental wheat crops, we consider arable crop production as a coldspot for azole resistance development, in contrast to previously reported flower bulb waste heaps. This study also shows that, in addition to azole resistance, several lineages of A. fumigatus carrying TR-based CYP51A variants have also developed acquired resistance to methyl benzimidazole carbamate, quinone outside inhibitor and succinate dehydrogenase (Sdh) inhibitor fungicides through target-site alterations in the corresponding fungicide target proteins; beta-tubulin (F200Y), cytochrome b (G143A), and Sdh subunit B (H270Y and H270R), respectively. Molecular typing showed that several multi-fungicide resistant strains found in agricultural soils in this study were clonal as identical isolates have been found earlier in the environment and/or in patients. Further research on the spread of different fungicide-resistant alleles from the wider environment to patients and vice versa can inform optimal practices to tackle the further spread of antifungal resistance in A. fumigatus populations and to safeguard the efficacy of azoles for future treatment of invasive aspergillosis
Epidemiological studies of pan-azole resistant Aspergillus fumigatus populations sampled during tulip cultivation show clonal expansion with acquisition of multi-fungicide resistance as potential driver
Pan-azole resistant isolates are found in clinical and environmental Aspergillus fumigatus (Af) populations. Azole resistance can evolve in both settings, with Af directly targeted by antifungals in patients and, in the environment, Af unintendedly exposed to fungicides used for material preservation and plant disease control. Resistance to non-azole fungi-cides, including methyl benzimidazole carbamates (MBCs), quinone outside inhibitors (QoIs) and succinate dehydrogenase inhibitors (SDHIs), have recently been reported. These fungicide groups are not used in medicine but can play an important role in further spread of pan-azole resistant genotypes. We investigated the multi-fungicide resistance status and genetic diversity of Af populations sampled from tulip field soils, tulip peel waste and flower compost heaps using fungicide sensitivity testing and a range of genotyping tools, including STRAf typing and sequencing of fungicide resistant alleles. Two major clones were present in the tulip bulb population. Comparisons with clinical isolates and literature data revealed that several common clonal lineages of TR34/L98H and TR46/Y121F/T289A strains that have expanded successfully in the environment have also acquired resistance to MBC, QoI and/or SDHI fungicides. Strains carrying multiple fungicide resistant alleles have an advantage in environments where residues of multiple fungicides belonging to different modes of action are presen
Evaluation of a patient and public involvement training programme for researchers at a large biomedical research centre in the UK
Objectives: To design, deliver and evaluate a programme of training workshops for biomedical researchers aimed at building confidence and skills in actively involving patients and the public (PPI) in research.
Design: A bespoke programme of training workshops in PPI aimed at researchers.
Setting: A large National Institute for Health Research Biomedical Research Centre in London and several partner organisations.
Participants: 721 scientists, clinicians and research managers attending dedicated training in PPI at a major London NHS (National Health Service)–university partnership.
Interventions: A programme of 72 training workshops, designed to build practical skills and confidence for researchers working with patients and the public in research, was delivered at a major research-active NHS:university partnership. An iterative approach was taken to the programme, with the content of the workshops continually reviewed and refreshed to respond to the needs of researchers. Surveys before, immediately following and 6 months after training investigated the impact on researchers’ confidence and skills in PPI work, and the kind of PPI they subsequently carried out.
Results: Training brought about immediate marked increases in researchers’ self-reported confidence to carry out PPI activities within their research, and in their knowledge of good practice. The evaluation indicates that workshop attendees were more likely to involve patients in their research following training. Researchers tended to involve patients and the public in a range of areas, including input to study design and patient information, in particular.
Conclusions: When positioned within a broader organisational strategy for PPI in research, such training has an important role to play in progressing PPI in a major research partnership. Training appeared to provide the confidence needed to carry out PPI which enabled further development of confidence and skills. Involving researchers who have attended the training in the ongoing development of the programme and bringing in patients to the training programme are key next steps
A Heteroscedastic Bayesian Generalized Logistic Regression Model with Application to Scaling Problems
Power law scaling models have been used to understand the complexity of systems as diverse as cities, neurological activity, and rainfall and lightning. In the scaling framework, power laws and standard linear regression methods are widely used to estimate model parameters with assumed normality and fixed variance. Generalized linear models (GLM) can accommodate a wider range of distributions where the chosen distribution must meet the assumptions of the data to prevent model bias. We present a widely applicable Bayesian generalized logistic regression (BGLR) framework to more flexibly model a continuous real response addressing skew and heteroscedasticity. The Generalized Logistic Distribution (GLD) was selected to flexibly model skewed continuous data. This resulted in a nonlinear posterior distribution which may not have an analytical solution which can be solved numerically with Markov Chain Monte Carlo (MCMC) methods. We compared the BGLR model to standard and Bayesian normal models having fixed and varying variance when fitting power laws to 759 days of COVID-19 data. The BGLR yielded information beyond existing methods about the evolution of skew and skedasticity while revealing parameter bias of widely used methods. The BGLR flexibly modelled the complex characteristics necessary for an improved understanding of the propagation and dynamics of this infectious disease. The model is generally applicable and can be used as a template for modeling complexity with other distributions
Human notochordal cell transcriptome unveils potential regulators of cell function in the developing intervertebral disc
The adult nucleus pulposus originates from the embryonic notochord, but loss of notochordal cells with skeletal maturity in humans is thought to contribute to the onset of intervertebral disc degeneration. Thus, defining the phenotype of human embryonic/fetal notochordal cells is essential for understanding their roles and for development of novel therapies. However, a detailed transcriptomic profiling of human notochordal cells has never been achieved. In this study, the notochord-specific marker CD24 was used to specifically label and isolate (using FACS) notochordal cells from human embryonic and fetal spines (7.5-14 weeks post-conception). Microarray analysis and qPCR validation identified CD24, STMN2, RTN1, PRPH, CXCL12, IGF1, MAP1B, ISL1, CLDN1 and THBS2 as notochord-specific markers. Expression of these markers was confirmed in nucleus pulposus cells from aged and degenerate discs. Ingenuity pathway analysis revealed molecules involved in inhibition of vascularisation (WISP2, Noggin and EDN2) and inflammation (IL1-RN) to be master regulators of notochordal genes. Importantly, this study has, for the first time, defined the human notochordal cell transcriptome and suggests inhibition of inflammation and vascularisation may be key roles for notochordal cells during intervertebral disc development. The molecules and pathways identified in this study have potential for use in developing strategies to retard/prevent disc degeneration, or regenerate tissue.This research was funded by Arthritis Research UK (reference 21165 to SMR/JAH/LW) and the Henry Smith Charity (to JAH/SMR/MH). RRP was supported by a grant from the Programme for Advanced Medical Education, sponsored by Fundacão Calouste Gulbenkian, fundação Champalimaud, Ministério da Saúde, Fundação para a Ciência e Tecnologia and Apifarma, Portugal. Support was also received from the UK Medical Research Council (MR/J003352/1 to KPH), the Wellcome Trust (NAH was a senior fellow in clinical science, 088566; additional support from grant, 097820), and the British Council (14BX15NHBG to NAH). Consumable and technical support for this project (Sonal Patel) was funded by the National Institute for Health Research Manchester Musculoskeletal Biomedical Research Unit. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research, or the Department of Health. We are very grateful to all women who consented to take part in our research programme and for the assistance of research nurses and clinical colleagues at Manchester University NHS Foundation Trust. The authors would like to thank Prof Kathy Cheah and group for advice regarding the identification of sex-specific markers within microarray datasets.info:eu-repo/semantics/publishedVersio
Ultrasonic Phased-Array Characterization for NDE Applications
Southwest Research Institute (SwRI) recently fabricated and delivered the 100-channel Ultrasonic Phased-Array Testbed System (UPATS) for NASA's Langley Research Center. NASA prepared the specifications and provided the funding to develop UPATS in order to provide a tool for the improvement of ultrasonic nondestructive evaluation (NDE) and characterization of materials. UPATS incorporates state-of-the-art phased-array concepts such as beam steering, focusing, apodization, and phase-sensitive detection which make it possible to develop more sophisticated testing methodologies. It also can be used to investigate fundamental ultrasonic propagation and detection phenomena such as refraction, diffraction, scattering, and beam broadening
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