Purpose
Normative scores (norms) allow for comparisons between population(s) of interest and the general population, which is useful for burden of disease studies and cost-effectiveness analysis. The ...primary aim of this study was to estimate US visual analogue scale (EQ VAS) and utility-based norms for the EQ-5D-5L using the face-to-face sample. The secondary aim was to compare norms estimated in the face-to-face and online populations.
Methods
This study estimated population norms from two general population surveys: (a) face-to-face and (b) online. In these surveys, respondents provided their health state using the EQ-5D-5L health classifier and the EQ VAS. Descriptive statistics, including mean, standard deviation (SD), 95% confidence interval, and median for the 5L utility and EQ VAS were estimated for each sample and across relevant respondent characteristics to serve as the basis for US EQ-5D-5L norms
Results
Face-to-face sample respondents (
n
= 1134) were representative of the US adult general population. In this sample, mean (SD) utility decreased with increasing age until age 45 or greater (age 45–54: 0.816 (0.249) age 55–64: 0.815 (0.243) age 65–74: 0.824 (0.217) age 75 + : 0.811 (0.218)). With increasing age, more problems were reported on all dimensions except anxiety/depression; a smaller proportion of respondents age 65 and older reported problems with anxiety/depression (23.8%) as compared to the youngest respondents (42.1%). Online (
n
= 2018) mean utility and EQ VAS values were consistently lower than the face-to-face sample.
Conclusions
The availability of US EQ-5D-5L norms facilitates interpretation and understanding of general population and patient health.
Small extracellular vesicles (EVs) are 50–200 nm vesicles secreted by most cells. They are considered as mediators of intercellular communication, and EVs from specific cell types, in particular ...mesenchymal stem/stromal cells (MSCs), offer powerful therapeutic potential, and can provide a novel therapeutic strategy. They appear promising and safe (as EVs are non‐self‐replicating), and eventually MSC‐derived EVs (MSC‐EVs) may be developed to standardized, off‐the‐shelf allogeneic regenerative and immunomodulatory therapeutics. Promising pre‐clinical data have been achieved using MSCs from different sources as EV‐producing cells. Similarly, a variety EV isolation and characterization methods have been applied. Interestingly, MSC‐EVs obtained from different sources and prepared with different methods show in vitro and in vivo therapeutic effects, indicating that isolated EVs share a common potential. Here, well‐characterized and controlled, publicly available proteome profiles of MSC‐EVs are compared to identify a common MSC‐EV protein signature that might be coupled to the MSC‐EVs’ common therapeutic potential. This protein signature may be helpful in developing MSC‐EV quality control platforms required to confirm the identity and test for the purity of potential therapeutic MSC‐EVs.
Most of the theoretical and computational descriptions of the phase behavior of block copolymers describe the chain ensembles of perfect and uniform polymers. In contrast, experimental studies on ...block copolymers always employ materials with disperse molecular makeup. Although most polymers are so-called monodisperse, they still have a molecular weight dispersity. Here, we describe the synthesis and properties of a series of discrete length diblock co-oligomers, based on oligo-dimethylsiloxane (oDMS) and oligo-lactic acid (oLA), diblock co-oligomers with highly noncompatible blocks. By utilizing an iterative synthetic protocol, co-oligomers with molar masses up to 6901 Da, ultralow molar mass dispersities ( Đ ≤ 1.00002), and unique control over the co-oligomer composition are synthesized and characterized. This specific block co-oligomer required the development of a new divergent strategy for the oDMS structures by which both bis- and monosubstituted oDMS derivatives up to 59 Si-atoms became available. The incompatibility of the two blocks makes the final coupling more demanding the longer the blocks become. These optimized synthetic procedures granted access to multigram quantities of most of the block co-oligomers, useful to study the lower limits of block copolymer phase segregation in detail. Cylindrical, gyroid, and lamellar nanostructures, as revealed by DSC, SAXS, and AFM, were generated. The small oligomeric size of the block co-oligomers resulted in exceptionally small feature sizes (down to 3.4 nm) and long-range organization.
Kidney transplant recipients (KTR) may be at increased risk of adverse COVID‐19 outcomes, due to prevalent comorbidities and immunosuppressed status. Given the global differences in COVID‐19 policies ...and treatments, a robust assessment of all evidence is necessary to evaluate the clinical course of COVID‐19 in KTR. Studies on mortality and acute kidney injury (AKI) in KTR in the World Health Organization COVID‐19 database were systematically reviewed. We selected studies published between March 2020 and January 18th 2021, including at least five KTR with COVID‐19. Random‐effects meta‐analyses were performed to calculate overall proportions, including 95% confidence intervals (95% CI). Subgroup analyses were performed on time of submission, geographical region, sex, age, time after transplantation, comorbidities, and treatments. We included 74 studies with 5559 KTR with COVID‐19 (64.0% males, mean age 58.2 years, mean 73 months after transplantation) in total. The risk of mortality, 23% (95% CI: 21%–27%), and AKI, 50% (95% CI: 44%–56%), is high among KTR with COVID‐19, regardless of sex, age and comorbidities, underlining the call to accelerate vaccination programs for KTR. Given the suboptimal reporting across the identified studies, we urge researchers to consistently report anthropometrics, kidney function at baseline and discharge, (changes in) immunosuppressive therapy, AKI, and renal outcome among KTR.
This systematic review and meta‐analysis on COVID‐19 in kidney transplant recipients reveals high global mortality rates and provides recommendations for reporting of studies in future pandemics.
Microtubules are essential for polarized transport in neurons, but how their organization guides motor proteins to axons or dendrites is unclear. Because different motors recognize distinct ...microtubule properties, we used optical nanoscopy to examine the relationship between microtubule orientations, stability, and modifications. Nanometric tracking of motors to super-resolve microtubules and determine their polarity revealed that in dendrites, stable and acetylated microtubules are mostly oriented minus-end out, while dynamic and tyrosinated microtubules are oriented oppositely. In addition, microtubules with similar orientations and modifications form bundles that bias transport. Importantly, because the plus-end-directed Kinesin-1 selectively interacts with acetylated microtubules, this organization guides this motor out of dendrites and into axons. In contrast, Kinesin-3 prefers tyrosinated microtubules and can enter both axons and dendrites. This separation of distinct microtubule subsets into oppositely oriented bundles constitutes a key architectural principle of the neuronal microtubule cytoskeleton that enables polarized sorting by different motor proteins.
•Motor-based nanoscopy enables direct observation of microtubule (MT) polarity•In neurons, MTs organize into polarized bundles that locally bias transport•In dendrites, bundles of opposite orientation differ in stability and composition•Dendritic MTs bias Kinesin-1 transport toward the soma, ensuring axon selectivity
Tas et al. use optical nanoscopy to show that dendritic microtubules of opposite orientation differ in stability and composition and recruit different motor proteins. This explains why some motor proteins can move into dendrites while others can only enter axons.
Monodisperse oligodimethylsiloxanes end-functionalized with the hydrogen-bonding ureidopyrimidinone (UPy) motif undergo phase separation between their aromatic end groups and dimethylsiloxane ...midblocks to form ordered nanostructures with domain spacings of <5 nm. The self-assembly behavior of these well-defined oligomers resembles that of high degree of polymerization (N)–high block interaction parameter (χ) linear diblock copolymers despite their small size. Specifically, the phase morphology varies from lamellar to hexagonal to body-centered cubic with increasing asymmetry in molecular volume fraction. Mixing molecules with different molecular weights to give dispersity >1.13 results in disorder, showing importance of molecular monodispersity for ultrasmall ordered phase separation. In contrast, oligodimethylsiloxanes end-functionalized with an O-benzylated UPy derivative self-assemble into lamellar nanostructures regardless of volume fraction because of the strong preference of the end groups to aggregate in a planar geometry. Thus, these molecules display more classically liquid-crystalline self-assembly behavior where the lamellar bilayer thickness is determined by the siloxane midblock. Here the lamellar nanostructure is tolerant to molecular polydispersity. We show the importance of end groups in high χ–low N block molecules, where block-copolymer-like self-assembly in our UPy-functionalized oligodimethylsiloxanes relies upon the dominance of phase separation effects over directional end group aggregation.
Angioedema is defined as localized and self‐limiting edema of the subcutaneous and submucosal tissue, due to a temporary increase in vascular permeability caused by the release of vasoactive ...mediator(s). When angioedema recurs without significant wheals, the patient should be diagnosed to have angioedema as a distinct disease. In the absence of accepted classification, different types of angioedema are not uniquely identified. For this reason, the European Academy of Allergy and Clinical Immunology gave its patronage to a consensus conference aimed at classifying angioedema. Four types of acquired and three types of hereditary angioedema were identified as separate forms from the analysis of the literature and were presented in detail at the meeting. Here, we summarize the analysis of the data and the resulting classification of angioedema.
Purpose
Veno-arterial extracorporeal life support (ECLS) is increasingly used in patients during cardiac arrest and cardiogenic shock, to support both cardiac and pulmonary function. We performed a ...systematic review and meta-analysis of cohort studies comparing mortality in patients treated with and without ECLS support in the setting of refractory cardiac arrest and cardiogenic shock complicating acute myocardial infarction.
Methods
We systematically searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and the publisher subset of PubMed updated to December 2015. Thirteen studies were included of which nine included cardiac arrest patients (
n
= 3098) and four included patients with cardiogenic shock after acute myocardial infarction (
n
= 235). Data were pooled by a Mantel-Haenzel random effects model and heterogeneity was examined by the
I
2
statistic.
Results
In cardiac arrest, the use of ECLS was associated with an absolute increase of 30 days survival of 13 % compared with patients in which ECLS was not used 95 % CI 6–20 %;
p
< 0.001; number needed to treat (NNT) 7.7 and a higher rate of favourable neurological outcome at 30 days (absolute risk difference 14 %; 95 % CI 7–20 %;
p
< 0.0001; NNT 7.1). Propensity matched analysis, including 5 studies and 438 patients (219 in both groups), showed similar results. In cardiogenic shock, ECLS showed a 33 % higher 30-day survival compared with IABP (95 % CI, 14–52 %;
p
< 0.001; NNT 13) but no difference when compared with TandemHeart/Impella (−3 %; 95 % CI −21 to 14 %;
p
= 0.70; NNH 33).
Conclusions
In cardiac arrest, the use of ECLS was associated with an increased survival rate as well as an increase in favourable neurological outcome. In the setting of cardiogenic shock there was an increased survival with ECLS compared with IABP.
•This paper surveys over 200 papers using explainable artificial intelligence (XAI) in deep learning-based medical image analysis.•The surveyed papers are classified according to an XAI ...framework.•Trends and future perspectives for XAI in medical image analysis are identified.
With an increase in deep learning-based methods, the call for explainability of such methods grows, especially in high-stakes decision making areas such as medical image analysis. This survey presents an overview of explainable artificial intelligence (XAI) used in deep learning-based medical image analysis. A framework of XAI criteria is introduced to classify deep learning-based medical image analysis methods. Papers on XAI techniques in medical image analysis are then surveyed and categorized according to the framework and according to anatomical location. The paper concludes with an outlook of future opportunities for XAI in medical image analysis.
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Smart energy grids and smart meters are commonly expected to promote more sustainable ways of living. This paper presents a conceptual framework for analysing the different ways in which smart grid ...developments shape – and are shaped by – the everyday lives of residents. Drawing upon theories of social practices and the concept of informational governance, the framework discerns three categories of ‘information flows’: flows between household-members, flows between households and energy service providers, and flows between local and distant households. Based on interviews with Dutch stakeholders and observations at workshops we examine, for all three information flows, the changes in domestic energy practices and the social relations they help to create. The analysis reveals that new information flows may not produce more sustainable practices in linear and predictable ways. Instead, changes are contextual and emergent. Second, new possibilities for information sharing between households open up a terrain for new practices. Third, information flows affect social relationships in ways as illustrated by the debates on consumer privacy in the Netherlands. An exclusive focus on privacy, however, deviates attention from opportunities for information disclosure by energy providers, and from the significance of transparency issues in redefining relationships both within and between households.
•Smart grids generate three key new information flows that affect social relations.•Practice theory can reveal the ways in which households handle/govern information.•Householders show ambivalence about the workings of the different information flows.•Policies should account for the ‘bright’ as well as the ‘dark’ sides of information.
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