Automated deep learning segmentation of high-resolution 7 T postmortem MRI for quantitative analysis of structure-pathology correlations in neurodegenerative diseases

Postmortem MRI allows brain anatomy to be examined at high resolution and to link pathology measures with morphometric measurements. However, automated segmentation methods for brain mapping in postmortem MRI are not well developed, primarily due to limited availability of labeled datasets, and heterogeneity in scanner hardware and acquisition protocols. In this work, we present a high resolution of 135 postmortem human brain tissue specimens imaged at 0.3 mm$^{3}$ isotropic using a T2w sequence on a 7T whole-body MRI scanner. We developed a deep learning pipeline to segment the cortical mantle by benchmarking the performance of nine deep neural architectures, followed by post-hoc topological correction. We then segment four subcortical structures (caudate, putamen, globus pallidus, and thalamus), white matter hyperintensities, and the normal appearing white matter. We show generalizing capabilities across whole brain hemispheres in different specimens, and also on unseen images acquired at 0.28 mm^3 and 0.16 mm^3 isotropic T2*w FLASH sequence at 7T. We then compute localized cortical thickness and volumetric measurements across key regions, and link them with semi-quantitative neuropathological ratings. Our code, Jupyter notebooks, and the containerized executables are publicly available at: https://pulkit-khandelwal.github.io/exvivo-brain-upennComment: Preprint submitted to NeuroImage Project website: https://pulkit-khandelwal.github.io/exvivo-brain-upen

Neuroanatomical and cellular degeneration associated with a social disorder characterized by new ritualistic belief systems in a TDP-C patient vs. a Pick patient

Frontotemporal dementia (FTD) is a spectrum of clinically and pathologically heterogenous neurodegenerative dementias. Clinical and anatomical variants of FTD have been described and associated with underlying frontotemporal lobar degeneration (FTLD) pathology, including tauopathies (FTLD-tau) or TDP-43 proteinopathies (FTLD-TDP). FTD patients with predominant degeneration of anterior temporal cortices often develop a language disorder of semantic knowledge loss and/or a social disorder often characterized by compulsive rituals and belief systems corresponding to predominant left or right hemisphere involvement, respectively. The neural substrates of these complex social disorders remain unclear. Here, we present a comparative imaging and postmortem study of two patients, one with FTLD-TDP (subtype C) and one with FTLD-tau (subtype Pick disease), who both developed new rigid belief systems. The FTLD-TDP patient developed a complex set of values centered on positivity and associated with specific physical and behavioral features of pigs, while the FTLD-tau patient developed compulsive, goal-directed behaviors related to general themes of positivity and spirituality. Neuroimaging showed left-predominant temporal atrophy in the FTLD-TDP patient and right-predominant frontotemporal atrophy in the FTLD-tau patient. Consistent with antemortem cortical atrophy, histopathologic examinations revealed severe loss of neurons and myelin predominantly in the anterior temporal lobes of both patients, but the FTLD-tau patient showed more bilateral, dorsolateral involvement featuring greater pathology and loss of projection neurons and deep white matter. These findings highlight that the regions within and connected to anterior temporal lobes may have differential vulnerability to distinct FTLD proteinopathies and serve important roles in human belief systems

AVONET: morphological, ecological and geographical data for all birds

Functional traits offer a rich quantitative framework for developing and testing theories in evolutionary biology, ecology and ecosystem science. However, the potential of functional traits to drive theoretical advances and refine models of global change can only be fully realised when species‐level information is complete. Here we present the AVONET dataset containing comprehensive functional trait data for all birds, including six ecological variables, 11 continuous morphological traits, and information on range size and location. Raw morphological measurements are presented from 90,020 individuals of 11,009 extant bird species sampled from 181 countries. These data are also summarised as species averages in three taxonomic formats, allowing integration with a global phylogeny, geographical range maps, IUCN Red List data and the eBird citizen science database. The AVONET dataset provides the most detailed picture of continuous trait variation for any major radiation of organisms, offering a global template for testing hypotheses and exploring the evolutionary origins, structure and functioning of biodiversity

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Preventive Democracy in South Asia: Parliamentary Government in Bangladesh, India and Sri Lanka

Digital subtraction radiography serves angiography [1] and other medical applications successfully to extract minute x-ray signals from noisy backgrounds. Verhoeven [2] demonstrated that detecting surprisingly small changes in x-ray absorption makes this technique useful for industrial applications as well. I detect very small areal density differences and also wires as small as 2 µm in diameter although the spatial resolution of my x-ray apparatus is 1 mm

Impact of physician-assisted triage on timing of antibiotic delivery in patients admitted to the hospital with community-acquired pneumonia (CAP).

BACKGROUND: Time to antibiotic delivery in patients with diagnosis of pneumonia is a publicly reported quality measure. OBJECTIVE: We aim to describe the impact of emergency department (ED) physician-assisted triage (PAT) on The Joint Commission (TJC) and Centers for Medicare and Medicaid Services (CMS) pneumonia core quality measures of timing to antibiotic delivery. METHODS: Retrospective case series studies of patients admitted to the hospital through the ED with diagnosis of community-acquired pneumonia were identified over a period of 48 months. Patients were included in the study if they met TJC/CMS PN-5 (antibiotic timing) criteria. We compared antibiotic delivery timing before and after implementation of PAT in moderate-acuity patients using Wilcoxon rank sum tests. A linear regression analysis was done to account for age, sex, ED volume, and acuity level. RESULTS: A total of 659 patients were identified: 497 patients and 162 patients enrolled pre- and post-implementation of a PAT, respectively. The median antibiotic delivery times for moderate-acuity patients during open hours of operation of PAT were 180min (pre) and 195min (post), p=0.027; this was unchanged when ED volume, age, sex, and acuity level were accounted for. A total of 43 patients (9%) and 13 patients (8%) failed to receive antibiotics within 6h of ED presentation before and after implementation of PAT, respectively. CONCLUSION: In this study, implementation of PAT did not result in overall decrease in antibiotic delivery time in patients admitted to the hospital with CAP. We postulate several explanations for this delay in antibiotic delivery time

T1-2 anal carcinoma requires elective inguinal radiation treatment: The results of Trans Tasman Radiation Oncology Group study TROG 99.02

Background and purpose: Elective inguinal irradiation increases morbidity. We describe outcomes of moderate intensity chemoradiation treating anal canal and adjacent pelvic nodes only. Material and methods: Forty patients with T1-2, N0 anal carcinoma were enrolled between March 1999 and March 2003. Inguinal nodes were NOT electively irradiated. The anal canal and regional pelvic nodes received 36 Gy/20# over 4 weeks, and 2 weeks later the anal canal was boosted with 14.4 Gy/8#. Chemotherapy was 5 fluorouracil 800 mg/m /day on days 1-4 and 36-39, and Mitomycin C 10 mg/m on day 1. Results: Median follow-up was 44 months. Complete response was 95%. Four year results were; overall survival 71%, local control 82%, and colostomy-free survival (including salvage) 85%. Inguinal failure occurred in 22.5% but was isolated in only 12.5%. Treatment was well tolerated acutely with no toxic deaths. Severe late toxicity occurred in 7.5%. Conclusions: This moderate dose 'non inguinal' chemoradiation regimen resulted in modest acute toxicity, minimal long term morbidity and local control in line with other series. However staging failed to identify 12.5% of patients whose isolated inguinal failure might have been prevented by elective irradiation. Without more effective staging, all patients should receive elective inguinal irradiation