The COVID-19 pandemic has had an enormous impact on human activity worldwide, in part due to many governments issuing stay-at-home orders and limiting the types of social interactions in which ...citizens can engage. Previous research has shown that social isolation can contribute to psychological distress. The impact of increased social isolation on mental health functioning during the COVID-19 crisis, as well as potential mechanisms to buffer this impact, have yet to be investigated. The current study explored the moderating role of psychological flexibility and related constructs on the relationships between social isolation and mental health outcomes during the COVID-19 pandemic. Cross-sectional data from 278 participants, the majority residing in the United States, were collected during a 3-week period from mid-April to early May 2020 via online survey. A series of hierarchical linear regression analyses indicated statistically significant relationships between social isolation and psychological distress (depression, anxiety, and stress), well-being, and valued living. Psychological inflexibility, intolerance of uncertainty, and emotional suppression significantly moderated these relationships in a number of instances. Greater psychological flexibility and acceptance of difficult experiences appeared to act as a buffer against the negative effects of increased social isolation, while amplifying the benefits of social connectedness. Implications for promoting mental health and buffering against the harmful effects of social isolation during the COVID-19 pandemic and beyond are discussed.
•Social isolation predicts negative psychological distress during COVID-19.•Psychological flexibility buffers negative impacts of isolation on distress.•Tolerance of uncertainty buffers negative impacts of social isolation on distress.•Psychological flexibility enhances beneficial effects of connectedness.•Psychological flexibility is a promising treatment target during COVID-19.
The
connectome provides large-scale connectivity and morphology information for the majority of the central brain of
. Using this data set, we provide a complete description of the
olfactory system, ...covering all first, second and lateral horn-associated third-order neurons. We develop a generally applicable strategy to extract information flow and layered organisation from connectome graphs, mapping olfactory input to descending interneurons. This identifies a range of motifs including highly lateralised circuits in the antennal lobe and patterns of convergence downstream of the mushroom body and lateral horn. Leveraging a second data set we provide a first quantitative assessment of inter- versus intra-individual stereotypy. Comparing neurons across two brains (three hemispheres) reveals striking similarity in neuronal morphology across brains. Connectivity correlates with morphology and neurons of the same morphological type show similar connection variability within the same brain as across two brains.
OBJECTIVETo update the 2001 American Academy of Neurology (AAN) guideline on mild cognitive impairment (MCI).
METHODSThe guideline panel systematically reviewed MCI prevalence, prognosis, and ...treatment articles according to AAN evidence classification criteria, and based recommendations on evidence and modified Delphi consensus.
RESULTSMCI prevalence was 6.7% for ages 60–64, 8.4% for 65–69, 10.1% for 70–74, 14.8% for 75–79, and 25.2% for 80–84. Cumulative dementia incidence was 14.9% in individuals with MCI older than age 65 years followed for 2 years. No high-quality evidence exists to support pharmacologic treatments for MCI. In patients with MCI, exercise training (6 months) is likely to improve cognitive measures and cognitive training may improve cognitive measures.
MAJOR RECOMMENDATIONSClinicians should assess for MCI with validated tools in appropriate scenarios (Level B). Clinicians should evaluate patients with MCI for modifiable risk factors, assess for functional impairment, and assess for and treat behavioral/neuropsychiatric symptoms (Level B). Clinicians should monitor cognitive status of patients with MCI over time (Level B). Cognitively impairing medications should be discontinued where possible and behavioral symptoms treated (Level B). Clinicians may choose not to offer cholinesterase inhibitors (Level B); if offering, they must first discuss lack of evidence (Level A). Clinicians should recommend regular exercise (Level B). Clinicians may recommend cognitive training (Level C). Clinicians should discuss diagnosis, prognosis, long-term planning, and the lack of effective medicine options (Level B), and may discuss biomarker research with patients with MCI and families (Level C).
To examine practice patterns and compare survival outcomes between total laryngectomy (TL) and larynx preservation chemoradiation (LP-CRT) in the setting of T4a larynx cancer, using a large national ...cancer registry.
Using the National Cancer Database, we identified 969 patients from 2003 to 2006 with T4a squamous cell larynx cancer receiving definitive treatment with either initial TL plus adjuvant therapy or LP-CRT. Univariate and multivariable logistic regression were used to assess predictors of undergoing surgery. Survival outcomes were compared using Kaplan-Meier and propensity score-adjusted and inverse probability of treatment-weighted Cox proportional hazards methods. Sensitivity analyses were performed to account for unmeasured confounders.
A total of 616 patients (64%) received LP-CRT, and 353 (36%) received TL. On multivariable logistic regression, patients with advanced nodal disease were less likely to receive TL (N2 vs N0, 26.6% vs 43.4%, odds ratio OR 0.52, 95% confidence interval CI 0.37-0.73; N3 vs N0, 19.1% vs 43.4%, OR 0.23, 95% CI 0.07-0.77), whereas patients treated in high case-volume facilities were more likely to receive TL (46.1% vs 31.5%, OR 1.78, 95% CI 1.27-2.48). Median survival for TL versus LP was 61 versus 39 months (P<.001). After controlling for potential confounders, LP-CRT had inferior overall survival compared with TL (hazard ratio 1.31, 95% CI 1.10-1.57), and with the inverse probability of treatment-weighted model (hazard ratio 1.25, 95% CI 1.05-1.49). This survival difference was shown to be robust on additional sensitivity analyses.
Most patients with T4a larynx cancer receive LP-CRT, despite guidelines suggesting TL as the preferred initial approach. Patients receiving LP-CRT had more advanced nodal disease and worse overall survival. Previous studies of (non-T4a) locally advanced larynx cancer showing no difference in survival between LP-CRT and TL may not apply to T4a disease, and patients should be counseled accordingly.
This Article seeks to provide in property legal theory an alternative to law-and-economics theory, the dominant mode of theorizing about property in contemporary legal scholarship. I call this ...alternative the social-obligation theory.
I argue that American property law, both on the private and public sides, includes a social-obligation norm, but that this norm has never been explicitly recognized as such nor systemically developed. I argue that a proper understanding of the social obligation explains a remarkably wide array of existing legal doctrine in American property law, ranging from the power of eminent domain to the modern public trust doctrine. In some cases, social obligation reaches the same result as law and economics, but in other cases it does not. Even if it reaches the same result as law and economics, social-obligation theory provides a superior explanation.
At a normative level, I argue that the version of the social-obligation norm that I develop here is morally superior to other candidates for the social-obligation norm. It is superior because it best promotes human flourishing, i.e., enabling individuals to live lives worthy of human dignity.
Drawing on Amartya Sen and Martha Nussbaum's capabilities approach (which itself is based on the Aristotelian notion that the human being is a social and political animal, not alone self-sufficient), the social-obligation theory holds that all individuals have an obligation to others in their respective communities to promote the capabilities that are essential to human flourishing (e.g., freedom, practical reasoning). For property owners, this has important consequences. If we accept the existence of an obligation to foster the capabilities necessary for human flourishing, and if we understand that obligation as extending to an obligation to share property, at least in surplus resources, then it follows that to enhance the abilities of others to flourish, in the predictable absence of adequate voluntary transfers, the state should be empowered and may even be obligated to compel the wealthy to share their surplus with the poor so that the latter can develop the necessary capabilities. None of this is meant to suggest that the state's power, even as it touches on the facilitation of the capabilities we are discussing, is unbounded. But the limits to the state's proper domain are supplied by the same principles that justify its action: the demands generated by the capabilities that facilitate human flourishing-freedom, practical rationality, and sociality, among others.
Brain extraction, or skull-stripping, is an essential pre-processing step in neuro-imaging that has a direct impact on the quality of all subsequent processing and analyses steps. It is also a key ...requirement in multi-institutional collaborations to comply with privacy-preserving regulations. Existing automated methods, including Deep Learning (DL) based methods that have obtained state-of-the-art results in recent years, have primarily targeted brain extraction without considering pathologically-affected brains. Accordingly, they perform sub-optimally when applied on magnetic resonance imaging (MRI) brain scans with apparent pathologies such as brain tumors. Furthermore, existing methods focus on using only T1-weighted MRI scans, even though multi-parametric MRI (mpMRI) scans are routinely acquired for patients with suspected brain tumors. In this study, we present a comprehensive performance evaluation of recent deep learning architectures for brain extraction, training models on mpMRI scans of pathologically-affected brains, with a particular focus on seeking a practically-applicable, low computational footprint approach, generalizable across multiple institutions, further facilitating collaborations. We identified a large retrospective multi-institutional dataset of n=3340 mpMRI brain tumor scans, with manually-inspected and approved gold-standard segmentations, acquired during standard clinical practice under varying acquisition protocols, both from private institutional data and public (TCIA) collections. To facilitate optimal utilization of rich mpMRI data, we further introduce and evaluate a novel ‘‘modality-agnostic training’’ technique that can be applied using any available modality, without need for model retraining. Our results indicate that the modality-agnostic approach11Publicly available source code: https://github.com/CBICA/BrainMaGe obtains accurate results, providing a generic and practical tool for brain extraction on scans with brain tumors.
•Accurate brain extraction on MRI scans in presence of diffuse gliomas is critical.•Comprehensive evaluation of prominent deep learning architectures, BET & FreeSurfer.•Multi-institutional data to test generalizability and to facilitate collaborations.•A novel “modality-agnostic” strategy to promote widespread application.
Purpose To evaluate whether compartmental analysis by using hybrid multidimensional magnetic resonance (MR) imaging can be used to diagnose prostate cancer and determine its aggressiveness. Materials ...and Methods Twenty-two patients with prostate cancer underwent preoperative 3.0-T MR imaging. Axial images were obtained with hybrid multidimensional MR imaging by using all combinations of echo times (47, 75, 100 msec) and b values of 0, 750, 1500 sec/mm
, resulting in a 3 × 3 array of data associated with each voxel. Volumes of the tissue components stroma, epithelium, and lumen were calculated by fitting the hybrid data to a three-compartment signal model, with distinct, paired apparent diffusion coefficient (ADC) and T2 values associated with each compartment. Volume fractions and conventional ADC and T2 were measured for regions of interest in sites of prostatectomy-verified malignancy (n = 28) and normal tissue (n = 71). Receiver operating characteristic (ROC) analysis was used to evaluate the performance of various parameters in differentiating prostate cancer from benign tissue. Results Compared with normal tissue, prostate cancer showed significantly increased fractional volumes of epithelium (23.2% ± 7.1 vs 48.8% ± 9.2, respectively) and reduced fractional volumes of lumen (26.4% ± 14.1 vs 14.0% ± 5.2) and stroma (50.5% ± 15.7 vs 37.2% ± 9.1) by using hybrid multidimensional MR imaging. The fractional volumes of tissue components show a significantly higher Spearman correlation coefficient with Gleason score (epithelium: ρ = 0.652, P = .0001; stroma: ρ = -0.439, P = .020; lumen: ρ = -0.390, P = .040) compared with traditional T2 values (ρ = -0.292, P = .132) and ADCs (ρ = -0.315, P = .102). The area under the ROC curve for differentiation of cancer from normal prostate was highest for fractional volume of epithelium (0.991), followed by fractional volumes of lumen (0.800) and stroma (0.789). Conclusion Fractional volumes of prostatic lumen, stroma, and epithelium change significantly when cancer is present. These parameters can be measured noninvasively by using hybrid multidimensional MR imaging and have the potential to improve the diagnosis of prostate cancer and determine its aggressiveness.
RSNA, 2018 Online supplemental material is available for this article.
This book surveys the leading modern theories of property – Lockean, libertarian, utilitarian/law-and-economics, personhood, Kantian and human flourishing – and then applies those theories to ...concrete contexts in which property issues have been especially controversial. These include redistribution, the right to exclude, regulatory takings, eminent domain and intellectual property. The book highlights the Aristotelian human flourishing theory of property, providing the most comprehensive and accessible introduction to that theory to date. The book's goal is neither to cover every conceivable theory nor to discuss every possible facet of the theories covered. Instead, it aims to make the major property theories comprehensible to beginners, without sacrificing accuracy or sophistication. The book will be of particular interest to students seeking an accessible introduction to contemporary theories of property, but even specialists will benefit from the book's lucid descriptions of contemporary debates.
BackgroundIvacaftor is the first cystic fibrosis transmembrane conductance regulator (CFTR) modulator demonstrating clinical benefit in patients with cystic fibrosis (CF). As ivacaftor is intended ...for chronic, lifelong use, understanding long-term effects is important for patients and healthcare providers.ObjectiveThis ongoing, observational, postapproval safety study evaluates clinical outcomes and disease progression in ivacaftor-treated patients using data from the US and the UK CF registries following commercial availability.MethodsAnnual analyses compare ivacaftor-treated and untreated matched comparator patients for: risks of death, transplantation, hospitalisation, pulmonary exacerbation; prevalence of CF-related complications and microorganisms and lung function changes in a subset of patients who initiated ivacaftor in the first year of commercial availability. Results from the 2014 analyses (2 and 3 years following commercial availability in the UK and USA, respectively) are presented here.ResultsAnalyses included 1256 ivacaftor-treated and 6200 comparator patients from the USA and 411 ivacaftor-treated and 2069 comparator patients from the UK. No new safety concerns were identified based on the evaluation of clinical outcomes included in the analyses. As part of safety evaluations, ivacaftor-treated US patients were observed to have significantly lower risks of death (0.6% vs 1.6%, p=0.0110), transplantation (0.2% vs 1.1%, p=0.0017), hospitalisation (27.5% vs 43.1%, p<0.0001) and pulmonary exacerbation (27.8% vs 43.3%, p<0.0001) relative to comparators; trends were similar in the UK. In both registries, ivacaftor-treated patients had a lower prevalence of CF-related complications and select microorganisms and had better preserved lung function.ConclusionsWhile general limitations of observational research apply, analyses revealed favourable results for clinically important outcomes among ivacaftor-treated patients, adding to the growing body of literature supporting disease modification by CFTR modulation with ivacaftor.EU PAS registration numberEUPAS4270
This paper presents a fully actuated robotic system for percutaneous prostate therapy under continuously acquired live magnetic resonance imaging (MRI) guidance. The system is composed of modular ...hardware and software to support the surgical workflow of intraoperative MRI-guided surgical procedures. We present the development of a 6-degree-of-freedom (DOF) needle placement robot for transperineal prostate interventions. The robot consists of a 3-DOF needle driver module and a 3-DOF Cartesian motion module. The needle driver provides needle cannula translation and rotation (2-DOF) and stylet translation (1-DOF). A custom robot controller consisting of multiple piezoelectric motor drivers provides precision closed-loop control of piezoelectric motors and enables simultaneous robot motion and MR imaging. The developed modular robot control interface software performs image-based registration, kinematics calculation, and exchanges robot commands and coordinates between the navigation software and the robot controller with a new implementation of the open network communication protocol OpenIGTLink. Comprehensive compatibility of the robot is evaluated inside a 3-T MRI scanner using standard imaging sequences and the signal-to-noise ratio loss is limited to 15%. The image deterioration due to the present and motion of robot demonstrates unobservable image interference. Twenty-five targeted needle placements inside gelatin phantoms utilizing an 18-gauge ceramic needle demonstrated 0.87-mm root-mean-square (RMS) error in 3-D Euclidean distance based on MRI volume segmentation of the image-guided robotic needle placement procedure.