Tuberous sclerosis complex (TSC) is an autosomal dominant tumor suppressor gene syndrome due to germline mutations in either TSC1 or TSC2. 10-15% of TSC individuals have no mutation identified (NMI) ...after thorough conventional molecular diagnostic assessment. 53 TSC subjects who were NMI were studied using next generation sequencing to search for mutations in these genes. Blood/saliva DNA including parental samples were available from all subjects, and skin tumor biopsy DNA was available from six subjects. We identified mutations in 45 of 53 subjects (85%). Mosaicism was observed in the majority (26 of 45, 58%), and intronic mutations were also unusually common, seen in 18 of 45 subjects (40%). Seventeen (38%) mutations were seen at an allele frequency < 5%, five at an allele frequency < 1%, and two were identified in skin tumor biopsies only, and were not seen at appreciable frequency in blood or saliva DNA. These findings illuminate the extent of mosaicism in TSC, indicate the importance of full gene coverage and next generation sequencing for mutation detection, show that analysis of TSC-related tumors can increase the mutation detection rate, indicate that it is not likely that a third TSC gene exists, and enable provision of genetic counseling to the substantial population of TSC individuals who are currently NMI.
We quantify the luminosity contribution of active galactic nuclei (AGNs) to the 12 m, mid-infrared (MIR; 5-38 m), and total IR (5-1000 m) emission in the local AGNs detected in the all-sky 70 month ...Swift/Burst Alert Telescope (BAT) ultrahard X-ray survey. We decompose the IR spectral energy distributions (SEDs) of 587 objects into the AGN and starburst components using templates for an AGN torus and a star-forming galaxy. This enables us to recover the emission from the AGN torus including the low-luminosity end, down to , which typically has significant host galaxy contamination. The sample demonstrates that the luminosity contribution of the AGN to the 12 m, the MIR, and the total IR bands is an increasing function of the 14-150 keV luminosity. We also find that for the most extreme cases, the IR pure-AGN emission from the torus can extend up to 90 m. The total IR AGN luminosity obtained through the IR SED decomposition enables us to estimate the fraction of the sky obscured by dust, i.e., the dust covering factor. We demonstrate that the median dust covering factor is always smaller than the median X-ray obscuration fraction above an AGN bolometric luminosity of . Considering that the X-ray obscuration fraction is equivalent to the covering factor coming from both the dust and gas, this indicates that an additional neutral gas component, along with the dusty torus, is responsible for the absorption of X-ray emission.
Psychology is currently facing a multilayered crisis stemming from the fact that the results of many psychological studies cannot be replicated (replication crisis), that psychological research has ...neglected cross-cultural and cross-temporal variation (universality crisis), and that many psychological theories are ill-developed and underspecified (theory crisis). In the present article, we use ideas derived from debates in theoretical and philosophical psychology as a basis for responding to all three crises. In short, we claim that psychological concepts are inherently vague in the sense that their meanings and the rules for their application are indeterminate. This does not imply that psychological concepts are ineffable or lack meaning. It implies, however, that hoping to arrive at a finite set of necessary and sufficient criteria that define psychological concepts once and for all is an illusion. From this, we deduce four recommendations for responding to psychology's crises. First, we argue that the replication crisis could be approached by paying more attention to the context conditions under which psychological realities and knowledge about these realities are being created. Second, we claim that the universality crisis can be alleviated by putting more effort into exploring variability across times and cultures. Third, we contend that acknowledging the language dependence of psychological research could be a fruitful way of addressing the theory crisis. Last, we show that embracing theoretical and methodological pluralism would be an antidote against psychology's crises in general. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
Critics of psychological measurement have accused quantitative psychologists of ignoring the empirical hypothesis that psychological phenomena are quantitative (Michell), or have claimed that it is ...impossible in principle to find out whether psychological phenomena are actually quantitative (Trendler). By drawing on Bennett and Hacker (2003), I argue that both criticisms do not go far enough because they sidestep the fundamental conceptual problem of the measurement debate: It is impossible to give concrete formulations of the question “Are psychological attributes quantitative?” without transgressing the boundaries of meaningful language. Conceptual confusions and questionable philosophical assumptions have contributed to the misguided idea that the quantity of psychological phenomena must or can be demonstrated empirically. First, the measurement debate is characterized by misleading examples and ambiguous terminology. Second, the idea of psychological measurement is inherently Cartesian. In summary, psychological measurement is even more problematic than Michell and Trendler have argued.
Coronavirus disease 2019 (COVID-19) is primarily a pulmonary disease, but also affects the cardiovascular system in multiple ways. In this review, we will summarise and put into perspective findings ...and debates relating to the diverse aspects of cardiovascular involvement of COVID-19. We will review evidence for the role of the renin-angiotensin-aldosterone system (RAAS), the risk of pre-existing cardiovascular disease in COVID-19 susceptibility and course, and the mechanism of acute and long-term myocardial injury. The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) uses membrane-bound angiotensin converting-enzyme-2 (ACE2) as a receptor for cell entry. ACE2 is part of an important counter-regulatory circuit antagonising the harmful effects of angiotensin II on lung and heart. Modulation of ACE2 may therefore affect disease susceptibility and disease course. However, observational clinical studies and one randomised trial have so far not yielded evidence for harmful or beneficial effects of blockers of the RAAS during COVID-19. Age, gender, and multi-morbidity all increase susceptibility to SARS-CoV-2. In contrast, pre-existing cardiovascular diseases do so only minimally, but they may aggravate the disease course. Direct SARS-CoV-2 infection of the heart tissue and myocytes is rare. Nevertheless, COVID-19 may lead to myocarditis-like acute cardiac injury, characterised by myocardial oedema, but lacking extensive myocyte loss and lymphocytic infiltration. Independent of this, increases in cardiac biomarkers (troponin, N-terminal pro-brain natriuretic peptide, D-dimer) are frequent, especially in the phase of severe systemic inflammation and acute respiratory distress syndrome, and quantitatively associated with poor outcome. The pulmonary infection may result initially in right ventricular dysfunction, but in cases with severe systemic infection hypoxia, hyperinflammation and cytokine storm heart failure may eventually ensue. Unlike other infections and inflammatory states, COVID-19 does not appear to trigger acute coronary syndromes. In children, even mild COVID-19 can induce a multisystem inflammatory syndrome with Kawasaki-like symptoms frequently accompanied by cardiogenic shock.
Established measurement practices have been criticized from various theoretical perspectives. The purpose of this article is to argue that quantitative research could be more defensible if contested ...assumptions about measurement were abandoned, and to illustrate this thesis with the example of the better-than-average-effect (BTAE). If research on the BTAE is conceptualized as an interpretive endeavor, one can provide arguments that do not rely on psychological measurement for the claim that the BTAE is evidence for self-delusion in people. I outline these arguments and elaborate them by discussing a typical study on the BTAE. Furthermore, I show how a measurement-free characterization of the BTAE reveals an important research gap and points to the specific scientific value of research on the BTAE. Finally, I offer three general suggestions for conducting future interpretive quantitative research: justifying why a quantitative method is suitable for investigating a certain phenomenon, providing a comprehensive interpretation of the numerical results, and exploring participants’ understanding of the study material.
Dual-antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor is the standard treatment for patients undergoing percutaneous coronary intervention. The availability of different P2Y12 ...receptor inhibitors (clopidogrel, prasugrel, ticagrelor) with varying levels of potency has enabled physicians to contemplate individualized treatment regimens, which may include escalation or de-escalation of P2Y12-inhibiting therapy. Indeed, individualized and alternative DAPT strategies may be chosen according to the clinical setting (stable coronary artery disease vs. acute coronary syndrome), the stage of the disease (early- vs. long-term treatment), and patient risk for ischemic and bleeding complications. A tailored DAPT approach may be potentially guided by platelet function testing (PFT) or genetic testing. Although the routine use of PFT or genetic testing in percutaneous coronary intervention–treated patients is not recommended, recent data have led to an update in guideline recommendations that allow considering selective use of PFT for DAPT de-escalation. However, guidelines do not expand on when to implement the selective use of such assays into decision making for personalized treatment approaches. Therefore, an international expert consensus group of key leaders from North America, Asia, and Europe with expertise in the field of antiplatelet treatment was convened. This document updates 2 prior consensus papers on this topic and summarizes the contemporary updated expert consensus recommendations for the selective use of PFT or genotyping in patients undergoing percutaneous coronary intervention.
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•Different P2Y12 inhibitors have enabled physicians to contemplate individualized treatment regimens.•In selective scenarios, PFT and genotyping may be used as optional tools for guiding treatment.•Further studies on DAPT de-escalation and escalation are needed to refine existing treatment options.
Proton transfer across single-layer graphene proceeds with large computed energy barriers and is therefore thought to be unfavourable at room temperature unless nanoscale holes or dopants are ...introduced, or a potential bias is applied. Here we subject single-layer graphene supported on fused silica to cycles of high and low pH, and show that protons transfer reversibly from the aqueous phase through the graphene to the other side where they undergo acid-base chemistry with the silica hydroxyl groups. After ruling out diffusion through macroscopic pinholes, the protons are found to transfer through rare, naturally occurring atomic defects. Computer simulations reveal low energy barriers of 0.61-0.75 eV for aqueous proton transfer across hydroxyl-terminated atomic defects that participate in a Grotthuss-type relay, while pyrylium-like ether terminations shut down proton exchange. Unfavourable energy barriers to helium and hydrogen transfer indicate the process is selective for aqueous protons.
Wood is a major pool of organic carbon that is highly resistant to decay, owing largely to the presence of lignin. The only organisms capable of substantial lignin decay are white rot fungi in the ...Agaricomycetes, which also contains non-lignin-degrading brown rot and ectomycorrhizal species. Comparative analyses of 31 fungal genomes (12 generated for this study) suggest that lignin-degrading peroxidases expanded in the lineage leading to the ancestor of the Agaricomycetes, which is reconstructed as a white rot species, and then contracted in parallel lineages leading to brown rot and mycorrhizal species. Molecular clock analyses suggest that the origin of lignin degradation might have coincided with the sharp decrease in the rate of organic carbon burial around the end of the Carboniferous period.
The profound and stimulating comments by Michell (2022), Tafreshi (2022), and Trendler (2022) push the measurement debate forward. Tafreshi provides arguments that are in line with my own position. ...While Michell is right in claiming that conceptualizations of psychological measurement are not necessarily Cartesian, I argue that the continuing influence of Cartesian thinking on conceptualizations of psychological measurement is evident in current definitions of psychological constructs. Moreover, I show that, contrary to Michell, it is meaningless to ask whether intelligence is quantitative. Michell and Trendler could counter this claim, but only at the cost of contradicting their stance that conceptual questions are not primary to the empirical questions surrounding psychological measurement. Beyond that, I contend that Trendler’s epistemological distinction of extensive versus intensive quantities does not compensate for the conceptual confusions inherent in his and Michell’s examples. Finally, I emphasize that all disputants agree that psychological measurement is a highly questionable idea.
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