Symptoms and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Positivity in the General Population in the United Kingdom

BACKGROUND: “Classic” symptoms (cough, fever, loss of taste/smell) prompt severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) testing in the United Kingdom. Studies have assessed the ability of different symptoms to identify infection, but few have compared symptoms over time (reflecting variants) and by vaccination status. METHODS: Using the COVID-19 Infection Survey, sampling households across the United Kingdom, we compared symptoms in PCR-positives vs PCR-negatives, evaluating sensitivity of combinations of 12 symptoms (percentage symptomatic PCR-positives reporting specific symptoms) and tests per case (TPC) (PCR-positives or PCR-negatives reporting specific symptoms/ PCR-positives reporting specific symptoms). RESULTS: Between April 2020 and August 2021, 27 869 SARS-CoV-2 PCR-positive episodes occurred in 27 692 participants (median 42 years), of whom 13 427 (48%) self-reported symptoms (“symptomatic PCR-positives”). The comparator comprised 3 806 692 test-negative visits (457 215 participants); 130 612 (3%) self-reported symptoms (“symptomatic PCR-negatives”). Symptom reporting in PCR-positives varied by age, sex, and ethnicity, and over time, reflecting changes in prevalence of viral variants, incidental changes (eg, seasonal pathogens (with sore throat increasing in PCR-positives and PCR-negatives from April 2021), schools reopening) and vaccination rollout. After May 2021 when Delta emerged, headache and fever substantially increased in PCR-positives, but not PCR-negatives. Sensitivity of symptom-based detection increased from 74% using “classic” symptoms, to 81% adding fatigue/weakness, and 90% including all 8 additional symptoms. However, this increased TPC from 4.6 to 5.3 to 8.7. CONCLUSIONS: Expanded symptom combinations may provide modest benefits for sensitivity of PCR-based case detection, but this will vary between settings and over time, and increases tests/case. Large-scale changes to targeted PCR-testing approaches require careful evaluation given substantial resource and infrastructure implications

EGFRvIII upregulates DNA mismatch repair resulting in increased temozolomide sensitivity of MGMT promoter methylated glioblastoma

The oncogene epidermal growth factor receptor variant III (EGFRvIII) is frequently expressed in glioblastomas (GBM) but its impact on therapy response is still under controversial debate. Here we wanted to test if EGFRvIII influences the sensitivity towards the alkylating agent temozolomide (TMZ). Therefore, we retrospectively analyzed the survival of 336 GBM patients, demonstrating that under standard treatment, which includes TMZ, EGFRvIII expression is associated with prolonged survival, but only in patients with O6-methylguanine-DNA methyltransferase (MGMT) promoter methylated tumors. Using isogenic GBM cell lines with endogenous EGFRvIII expression we could demonstrate that EGFRvIII increases TMZ sensitivity and results in enhanced numbers of DNA double-strand breaks and a pronounced S/G2-phase arrest after TMZ treatment. We observed a higher expression of DNA mismatch repair (MMR) proteins in EGFRvIII+ cells and patient tumor samples, which was most pronounced for MSH2 and MSH6. EGFRvIII-specific knockdown reduced MMR protein expression thereby increasing TMZ resistance. Subsequent functional kinome profiling revealed an increased activation of p38- and ERK1/2-dependent signaling in EGFRvIII expressing cells, which regulates MMR protein expression downstream of EGFRvIII. In summary, our results demonstrate that the oncoprotein EGFRvIII sensitizes a fraction of GBM to current standard of care treatment through the upregulation of DNA MMR

Subtypes of children with attention disabilities.

Subtypes of children with attentional problems were investigated using cluster analysis. Subjects were 9-year-old-elementary school children (N = 443). The test battery administered to these children comprised a comprehensive set of common attention tests, covering different aspects of attentional functioning, and a test of reading comprehension. Cluster analysis of these data yielded eight stable and reproducible clus¬ters. The test profiles of two subgroups were indicative of distinct attentional problems. One group ap¬peared deficient in speed of processing, the other in attentional control. A third subgroup showed a reading deficit. Two additional clusters had very poor and excellent performance on the whole battery, respec¬tively. Finally, three clusters were found with minor variations approximating average performance. The internal validity, that is, the adequacy and stability of the cluster solution, appeared to be reasonably good, as indicated by a variety of measures. The long-term stability over an 18-month period was also checked and found to be satisfactory

Symmetry and Topology in Superconductors - Odd-frequency pairing and edge states -

Superconductivity is a phenomenon where the macroscopic quantum coherence appears due to the pairing of electrons. This offers a fascinating arena to study the physics of broken gauge symmetry. However, the important symmetries in superconductors are not only the gauge invariance. Especially, the symmetry properties of the pairing, i.e., the parity and spin-singlet/spin-triplet, determine the physical properties of the superconducting state. Recently it has been recognized that there is the important third symmetry of the pair amplitude, i.e., even or odd parity with respect to the frequency. The conventional uniform superconducting states correspond to the even-frequency pairing, but the recent finding is that the odd-frequency pair amplitude arises in the spatially non-uniform situation quite ubiquitously. Especially, this is the case in the Andreev bound state (ABS) appearing at the surface/interface of the sample. The other important recent development is on the nontrivial topological aspects of superconductors. As the band insulators are classified by topological indices into (i) conventional insulator, (ii) quantum Hall insulator, and (iii) topological insulator, also are the gapped superconductors. The influence of the nontrivial topology of the bulk states appears as the edge or surface of the sample. In the superconductors, this leads to the formation of zero energy ABS (ZEABS). Therefore, the ABSs of the superconductors are the place where the symmetry and topology meet each other which offer the stage of rich physics. In this review, we discuss the physics of ABS from the viewpoint of the odd-frequency pairing, the topological bulk-edge correspondence, and the interplay of these two issues. It is described how the symmetry of the pairing and topological indices determines the absence/presence of the ZEABS, its energy dispersion, and properties as the Majorana fermions.Comment: 91 pages, 38 figures, Review article, references adde

Intuitive geometry and visuospatial working memory in children showing symptoms of nonverbal learning disabilities.

Visuospatial working memory (VSWM) and intuitive geometry were examined in two groups aged 11-13, one with children displaying symptoms of nonverbal learning disability (NLD; n = 16), and the other, a control group without learning disabilities (n = 16). The two groups were matched for general verbal abilities, age, gender, and socioeconomic level. The children were presented with simple storage and complex-span tasks involving VSWM and with the intuitive geometry task devised by Dehaene, Izard, Pica, and Spelke (2006 ). Results revealed that the two groups differed in the intuitive geometry task. Differences were particularly evident in Euclidean geometry and in geometrical transformations. Moreover, the performance of NLD children was worse than controls to a larger extent in complex-span than in simple storage tasks, and VSWM differences were able to account for group differences in geometry. Finally, a discriminant function analysis confirmed the crucial role of complex-span tasks involving VSWM in distinguishing between the two groups. Results are discussed with reference to the relationship between VSWM and mathematics difficulties in nonverbal learning disabilities

Evaluation of two sets of immunohistochemical and Western blot confirmatory methods in the detection of typical and atypical BSE cases

<p>Abstract</p> <p>Background</p> <p>Three distinct forms of bovine spongiform encephalopathy (BSE), defined as classical (C-), low (L-) or high (H-) type, have been detected through ongoing active and passive surveillance systems for the disease.</p> <p>The aim of the present study was to compare the ability of two sets of immunohistochemical (IHC) and Western blot (WB) BSE confirmatory protocols to detect C- and atypical (L- and H-type) BSE forms.</p> <p>Obex samples from cases of United States and Italian C-type BSE, a U.S. H-type and an Italian L-type BSE case were tested in parallel using the two IHC sets and WB methods.</p> <p>Results</p> <p>The two IHC techniques proved equivalent in identifying and differentiating between C-type, L-type and H-type BSE. The IHC protocols appeared consistent in the identification of PrP^Scdistribution and deposition patterns in relation to the BSE type examined. Both IHC methods evidenced three distinct PrP^Scphenotypes for each type of BSE: prevailing granular and linear tracts pattern in the C-type; intraglial and intraneuronal deposits in the H-type; plaques in the L-type.</p> <p>Also, the two techniques gave comparable results for PrP^Scstaining intensity on the C- and L-type BSE samples, whereas a higher amount of intraglial and intraneuronal PrP^Scdeposition on the H-type BSE case was revealed by the method based on a stronger demasking step.</p> <p>Both WB methods were consistent in identifying classical and atypical BSE forms and in differentiating the specific PrP^Scmolecular weight and glycoform ratios of each form.</p> <p>Conclusions</p> <p>The study showed that the IHC and WB BSE confirmatory methods were equally able to recognize C-, L- and H-type BSE forms and to discriminate between their different immunohistochemical and molecular phenotypes. Of note is that for the first time one of the two sets of BSE confirmatory protocols proved effective in identifying the L-type BSE form. This finding helps to validate the suitability of the BSE confirmatory tests for BSE surveillance currently in place.</p

NHR-49 Helps Germline-Less Worms Chew the Fat

In C. elegans, removal of the germline extends lifespan significantly. We demonstrate that the nuclear hormone receptor, NHR-49, enables the response to this physiological change by increasing the expression of genes involved in mitochondrial β-oxidation and fatty-acid desaturation. The coordinated augmentation of these processes is critical for germline-less animals to maintain their lipid stores and to sustain de novo fat synthesis during adulthood. Following germline ablation, NHR-49 is up-regulated in somatic cells by the conserved longevity determinants DAF-16/FOXO and TCER-1/TCERG1. Accordingly, NHR-49 overexpression in fertile animals extends their lifespan modestly. In fertile adults, nhr-49 expression is DAF-16/FOXO and TCER-1/TCERG1 independent although its depletion causes age-related lipid abnormalities. Our data provide molecular insights into how reproductive stimuli are integrated into global metabolic changes to alter the lifespan of the animal. They suggest that NHR-49 may facilitate the adaptation to loss of reproductive potential through synchronized enhancement of fatty-acid oxidation and desaturation, thus breaking down some fats ordained for reproduction and orchestrating a lipid profile conducive for somatic maintenance and longevity