Control systems have come to play an important role in the performance of modern vehicles with regards to meeting goals on low emissions and low fuel consumption. To achieve these goals, modeling, ...simulation, and analysis have become standard tools for the development of control systems in the automotive industry.
SARS-CoV-2-specific memory T cells will likely prove critical for long-term immune protection against COVID-19. Here, we systematically mapped the functional and phenotypic landscape of ...SARS-CoV-2-specific T cell responses in unexposed individuals, exposed family members, and individuals with acute or convalescent COVID-19. Acute-phase SARS-CoV-2-specific T cells displayed a highly activated cytotoxic phenotype that correlated with various clinical markers of disease severity, whereas convalescent-phase SARS-CoV-2-specific T cells were polyfunctional and displayed a stem-like memory phenotype. Importantly, SARS-CoV-2-specific T cells were detectable in antibody-seronegative exposed family members and convalescent individuals with a history of asymptomatic and mild COVID-19. Our collective dataset shows that SARS-CoV-2 elicits broadly directed and functionally replete memory T cell responses, suggesting that natural exposure or infection may prevent recurrent episodes of severe COVID-19.
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•Acute-phase SARS-CoV-2-specific T cells display an activated cytotoxic phenotype•Convalescent-phase SARS-CoV-2-specific T cells generate broad responses•Polyfunctional SARS-CoV-2-specific T cells also occur in seronegative individuals
Sekine et al. provide a functional and phenotypic map of SARS-CoV-2-specific T cells across the full spectrum of exposure, infection, and COVID-19 severity. They observe that SARS-CoV-2 elicits broadly directed and functionally replete memory T cells that may protect against recurrent episodes of severe COVID-19.
Cognitive recovery after anaesthesia and surgery is a concern for older adults, their families, and caregivers. Reports of patients who were ‘never the same’ prompted a scientific inquiry into the ...nature of what patients have experienced. In June 2018, the ASA Brain Health Initiative held a summit to discuss the state of the science on perioperative cognition, and to create an implementation plan for patients and providers leveraging the current evidence. This group included representatives from the AARP (formerly the American Association of Retired Persons), American College of Surgeons, American Heart Association, and Alzheimer's Association Perioperative Cognition and Delirium Professional Interest Area. This paper summarises the state of the relevant clinical science, including risk factors, identification and diagnosis, prognosis, disparities, outcomes, and treatment of perioperative neurocognitive disorders. Finally, we discuss gaps in current knowledge with suggestions for future directions and opportunities for clinical and translational projects.
The aim of the present study was to investigate the predictive ability for lung cancer of symptoms reported in an adaptive e-questionnaire, separately for never smokers, former smokers, and current ...smokers. Consecutive patients referred for suspected lung cancer were recruited between September 2014 and November 2015 from the lung clinic at the Karolinska University Hospital, Stockholm, Sweden. A total of 504 patients were later diagnosed with lung cancer (n = 310) or no cancer (n = 194). All participants answered an adaptive e-questionnaire with a maximum of 342 items, covering background variables and symptoms/sensations suspected to be associated with lung cancer. Stochastic gradient boosting, stratified on smoking status, was used to train and test a model for predicting the presence of lung cancer. Among never smokers, 17 predictors contributed to predicting lung cancer with 82% of the patients being correctly classified, compared with 26 predictors with an accuracy of 77% among current smokers and 36 predictors with an accuracy of 63% among former smokers. Age, sex, and education level were the most important predictors in all models.
With the increased interest in new PET tracers, gene-targeted therapy, immunoPET, and theranostics, other radioisotopes will be increasingly used in clinical PET scanners, in addition to
18
F. Some ...of the most interesting radioisotopes with prospective use in the new fields are not pure short-range β
+
emitters but can be associated with gamma emissions in coincidence with the annihilation radiation (prompt gamma), gamma-gamma cascades, intense Bremsstrahlung radiation, high-energy positrons that may escape out of the patient skin, and high-energy gamma rays that result in some
e
+
/
e
−
pair production. The high level of sophistication in data correction and excellent quantitative accuracy that has been reached for
18
F in recent years can be questioned by these effects. In this work, we review the physics and the scientific literature and evaluate the effect of these additional phenomena on the PET data for each of a series of radioisotopes:
11
C,
13
N,
15
O,
18
F,
64
Cu,
68
Ga,
76
Br,
82
Rb,
86
Y,
89
Zr,
90
Y, and
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I. In particular, we discuss the present complications arising from the prompt gammas, and we review the scientific literature on prompt gamma correction. For some of the radioisotopes considered in this work, prompt gamma correction is definitely needed to assure acceptable image quality, and several approaches have been proposed in recent years. Bremsstrahlung photons and
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Lu background were also evaluated.
Epidemics have historically been accompanied by stigma and discrimination. Disease-related stigma has often been shown to have severe consequences for physical, mental and social wellbeing and lead ...to barriers to diagnosis, treatment and prevention. The aims of this study were to investigate if a HIV-related stigma measure could be adapted and valid and reliable to measure COVID-19-related stigma, and also to investigate levels of self-reported stigma and related factors among people in Sweden with experience of COVID-19 and compare levels of COVID-19-related stigma versus HIV-related stigma among persons living with HIV who had experienced a COVID-19 event.
Cognitive interviews (n = 11) and cross-sectional surveys were made after the acute phase of the illness using a new 12-item COVID-19 Stigma Scale and the established 12-item HIV Stigma Scale in two cohorts (people who had experienced COVID-19 (n = 166/209, 79%) and people living with HIV who had experienced a COVID-19 event (n = 50/91, 55%). Psychometric analysis of the COVID-19 Stigma Scale was performed by calculating floor and ceiling effects, Cronbach's α and exploratory factor analysis. Levels of COVID-19 stigma between groups were analysed using the Mann-Whitney U test. Levels of COVID-19 and HIV stigma among people living with HIV with a COVID-19 event were compared using the Wilcoxon signed-rank test.
The COVID-19 cohort consisted of 88 (53%) men and 78 (47%) women, mean age 51 (19-80); 143 (87%) living in a higher and 22 (13%) in a lower income area. The HIV + COVID-19 cohort consisted of 34 (68%) men and 16 (32%) women, mean age 51 (26-79); 20 (40%) living in a higher and 30 (60%) in a lower income area. The cognitive interviews showed that the stigma items were easy to understand. Factor analysis suggested a four-factor solution accounting for 77% of the total variance. There were no cross loadings, but two items loaded on factors differing from the original scale. All subscales had acceptable internal consistency, showed high floor and no ceiling effects. There was no statistically significant difference between COVID-19 stigma scores between the two cohorts or between genders. People living in lower income areas reported more negative self-image and concerns about public attitudes related to COVID-19 than people in higher income areas (median score 3 vs 3 and 4 vs 3 on a scale from 3-12, Z = -1.980, p = 0.048 and Z = -2.023, p = 0.024, respectively). People from the HIV + COVID-19 cohort reported more HIV than COVID-19 stigma.
The adapted 12-item COVID-19 Stigma Scale may be valid and reliable for measurement of COVID-19-related stigma. However, specific items may need to be rephrased or replaced to better correspond to the COVID-19 context. People who had experienced COVID-19 reported low levels of COVID-19-related stigma in general but people from lower income areas had higher levels of negative self-image and concerns about public attitudes related to COVID-19 than people from areas with higher income, which may call for targeted interventions. Although exhibiting more pronounced HIV stigma levels, people living with HIV who had experienced COVID-19 reported COVID-19-related stigma of the same low magnitude as their peers not living with HIV.
The Covid-19 pandemic has had unprecedented effects on individual lives and livelihoods as well as on social, health, economic and political systems and structures across the world. This article ...derives from a unique collaboration between researchers and museums using rapid response crowdsourcing to document contemporary life among the general public during the pandemic crisis in Sweden.
We use qualitative analysis to explore the narrative crowdsourced submissions of the same 88 individuals at two timepoints, during the 1st and 2nd pandemic waves, about what they most fear in relation to the Covid-19 pandemic, and how their descriptions changed over time. In this self-selected group, we found that aspects they most feared generally concerned responses to the pandemic on a societal level, rather than to the Covid-19 disease itself or other health-related issues. The most salient fears included a broad array of societal issues, including general societal collapse and fears about effects on social and political interactions among people with resulting impact on political order. Notably strong support for the Swedish pandemic response was expressed, despite both national and international criticism.
This analysis fills a notable gap in research literature that lacks subjective and detailed investigation of experiences of the general public, despite recognition of the widespread effects of Covid-19 and its' management strategies. Findings address controversy about the role of experts in formulating and communicating strategy, as well as implications of human responses to existential threats. Based on this analysis, we call for broader focus on societal issues related to this existential threat and the responses to it.
Dendritic cells (DCs) and monocytes are crucial mediators of innate and adaptive immune responses during viral infection, but misdirected responses by these cells may contribute to immunopathology. ...Here, we performed high-dimensional flow cytometry-analysis focusing on mononuclear phagocyte (MNP) lineages in SARS-CoV-2-infected patients with moderate and severe COVID-19. We provide a deep and comprehensive map of the MNP landscape in COVID-19. A redistribution of monocyte subsets toward intermediate monocytes and a general decrease in circulating DCs was observed in response to infection. Severe disease coincided with the appearance of monocytic myeloid-derived suppressor cell-like cells and a higher frequency of pre-DC2. Furthermore, phenotypic alterations in MNPs, and their late precursors, were cell-lineage-specific and associated either with the general response against SARS-CoV-2 or COVID-19 severity. This included an interferon-imprint in DC1s observed in all patients and a decreased expression of the coinhibitory molecule CD200R in pre-DCs, DC2s, and DC3 subsets of severely sick patients. Finally, unsupervised analysis revealed that the MNP profile, alone, pointed to a cluster of COVID-19 nonsurvivors. This study provides a reference for the MNP response to SARS-CoV-2 infection and unravels mononuclear phagocyte dysregulations associated with severe COVID-19.
Valid and reliable instruments for the measurement of enacted, anticipated and internalised stigma in people living with HIV are crucial for mapping trends in the prevalence of HIV-related stigma and ...tracking the effectiveness of stigma-reducing interventions. Although longer instruments exist, e.g., the commonly used 40-item HIV Stigma Scale by Berger et al., a shorter instrument would be preferable to facilitate the inclusion of HIV stigma in more and broader surveys. Therefore, the aim of this work was to develop a substantially shorter, but still valid, version of the HIV Stigma Scale.
Data from a psychometric evaluation of the Swedish 40-item HIV Stigma Scale were reanalysed to create a short version with 12 items (three from each of the four stigma subscales: personalised stigma, disclosure concerns, concerns with public attitudes and negative self-image). The short version of the HIV stigma scale was then psychometrically tested using data from a national survey investigating stigma and quality of life among people living with HIV in Sweden (n = 880, mean age 47.9 years, 26% female).
The hypothesized factor structure of the proposed short version was replicated in exploratory factor analysis without cross loadings and confirmatory factor analysis supported construct validity with high standardised effects (>0.7) of items on the intended scales. The χ
test was statistically significant (χ
= 154.2, df = 48, p < 0.001), but alternate fit measures indicated acceptable fit (comparative fit index: 0.963, Tucker-Lewis index: 0.950 and root mean square error of approximation: 0.071). Corrected item-total correlation coefficients were >0.4 for all items, with a variation indicating that the broadness of the concept of stigma had been captured. All but two aspects of HIV-related stigma that the instrument is intended to cover were captured by the selected items in the short version. The aspects that did not lose any items were judged to have acceptable psychometric properties. The short version of the instrument showed higher floor and ceiling effects than the full-length scale, indicating a loss of sensitivity in the short version. Cronbach's α for the subscales were all >0.7.
Although being less sensitive in measurement, the proposed 12-item short version of the HIV Stigma Scale has comparable psychometric properties to the full-length scale and may be used when a shorter instrument is needed.
Objective:
Cognitive decline accompanies acute illness and surgery, especially in the elderly. Surgery engages the innate immune system that launches a systemic inflammatory response that, if ...unchecked, can cause multiple organ dysfunction. We sought to understand the mechanisms whereby the brain is targeted by the inflammatory response and how this can be resolved.
Methods:
C57BL/6J, Ccr2RFP/+Cx3cr1GFP/+, IkkF/F mice and LysM‐Cre/IkkF/F mice underwent stabilized tibial fracture operation under analgesia and general anesthesia. Separate cohorts of mice were tested for systemic and hippocampal inflammation, integrity of the blood–brain barrier (BBB), and cognition. The putative resolving effects of the cholinergic pathway on these postoperative responses were also studied.
Results:
Peripheral surgery disrupts the BBB via release of tumor necrosis factor‐alpha (TNFα), which facilitates the migration of macrophages into the hippocampus. Macrophage‐specific deletion of Ikappa B kinase (IKK)β, a central coordinator of TNFα signaling through activation of nuclear factor (NF) κB, prevents BBB disruption and macrophage infiltration in the hippocampus following surgery. Activation of the α7 subtype of nicotinic acetylcholine receptors, an endogenous inflammation‐resolving pathway, prevents TNFα‐induced NF‐κB activation, macrophage migration into the hippocampus, and cognitive decline following surgery.
Interpretation:
These data reveal the mechanisms for bidirectional communication between the brain and immune system following aseptic trauma. Pivotal molecular mechanisms can be targeted to prevent and/or resolve postoperative neuroinflammation and cognitive decline. ANN NEUROL 2011;70:986–995
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