Misleading assertions, unjustified assumptions, and additional limitations of a study by Patone et al., described in the article "Risk of Myocarditis After Sequential Doses of COVID-19 Vaccine and SARS-CoV-2 Infection by Age and Sex"

We describe several shortcomings of a study by Patone et al, whose findings were recently published in the American Heart Association Journal Circulation, including the following: * The study's principal conclusion, as initially stated, begins "Overall, the risk of myocarditis is greater after SARS-CoV-2 infection than after COVID-19 vaccination ...." However, Patone et al never attempt to assess the incidence of myocarditis in their study population following SARS-CoV-2 infection. Rather, they make an untenable assumption that all infections occurring in their study population are associated with (reported) positive COVID-19 tests. Using publicly available data from the UK's ONS and NHS, we show that Patone et al's estimates, for the unvaccinated, of myocarditis incidence associated with infection are likely overestimated by a factor of at least 1.58. * The method Patone et al use to compute the incidence of myocarditis among the unvaccinated after a positive COVID test may overestimate risk. The authors assume, without justification, that unvaccinated persons hospitalized during the study period with positive-test-associated myocarditis would later choose to vaccinate with the same probability as unvaccinated persons who have had a positive COVID test. We present a plausibility argument that suggests a possible further exaggeration of myocarditis risk post infection by a factor of 1.5. * Patone et al fail to discuss important limitations of their study with respect to guiding public health recommendations. For instance, at most 0.18% of SARS-CoV-2 cases that contributed to the study's finding were Omicron-variant cases. Thus, the study's estimates of myocarditis risk following infection do not speak to the risk following Omicron infection, which is recognized to be milder than that of previous variants.Comment: New section added (Section 4), conclusion updated (Section 6), 12 pages, 8 figure

Adjoints of rationally induced composition operators

We give an elementary proof of a formula recently obtained by Hammond, Moorhouse, and Robbins for the adjoint of a rationally induced composition operator on the Hardy space H^2. We discuss some variants and implications of this formula, and use it to provide a sufficient condition for a rationally induced composition operator adjoint to be a compact perturbation of a weighted composition operator.Comment: 21 pages, Published Versio

Varicella-Zoster viruses associated with post-herpetic neuralgia induce sodium current density increases in the ND7-23 Nav-1.8 neuroblastoma cell line

Post-herpetic neuralgia (PHN) is the most significant complication of herpes zoster caused by reactivation of latent Varicella-Zoster virus (VZV). We undertook a heterologous infection in vitro study to determine whether PHN-associated VZV isolates induce changes in sodium ion channel currents known to be associated with neuropathic pain. Twenty VZV isolates were studied blind from 11 PHN and 9 non-PHN subjects. Viruses were propagated in the MeWo cell line from which cell-free virus was harvested and applied to the ND7/23-Nav1.8 rat DRG x mouse neuroblastoma hybrid cell line which showed constitutive expression of the exogenous Nav 1.8, and endogenous expression of Nav 1.6 and Nav 1.7 genes all encoding sodium ion channels the dysregulation of which is associated with a range of neuropathic pain syndromes. After 72 hrs all three classes of VZV gene transcripts were detected in the absence of infectious virus. Single cell sodium ion channel recording was performed after 72 hr by voltage-clamping. PHN-associated VZV significantly increased sodium current amplitude in the cell line when compared with non-PHN VZV, wild-type (Dumas) or vaccine VZV strains ((POka, Merck and GSK). These sodium current increases were unaffected by acyclovir pre-treatment but were abolished by exposure to Tetrodotoxin (TTX) which blocks the TTX-sensitive fast Nav 1.6 and Nav 1.7 channels but not the TTX-resistant slow Nav 1.8 channel. PHN-associated VZV sodium current increases were therefore mediated in part by the Nav 1.6 and Nav 1.7 sodium ion channels. An additional observation was a modest increase in message levels of both Nav1.6 and Nav1.7 mRNA but not Nav 1.8 in PHN virally infected cells

Visualization of Genomic Changes by Segmented Smoothing Using an L0 Penalty

Copy number variations (CNV) and allelic imbalance in tumor tissue can show strong segmentation. Their graphical presentation can be enhanced by appropriate smoothing. Existing signal and scatterplot smoothers do not respect segmentation well. We present novel algorithms that use a penalty on the norm of differences of neighboring values. Visualization is our main goal, but we compare classification performance to that of VEGA

Molecular study of the perforin gene in familial hematological malignancies

Perforin gene (PRF1) mutations have been identified in some patients diagnosed with the familial form of hemophagocytic lymphohistiocytosis (HLH) and in patients with lymphoma. The aim of the present study was to determine whether patients with a familial aggregation of hematological malignancies harbor germline perforin gene mutations. For this purpose, 81 unrelated families from Tunisia and France with aggregated hematological malignancies were investigated. The variants detected in the PRF1 coding region amounted to 3.7% (3/81). Two of the three variants identified were previously described: the p.Ala91Val pathogenic mutation and the p.Asn252Ser polymorphism. A new p.Ala 211Val missense substitution was identified in two related Tunisian patients. In order to assess the pathogenicity of this new variation, bioinformatic tools were used to predict its effects on the perforin protein structure and at the mRNA level. The segregation of the mutant allele was studied in the family of interest and a control population was screened. The fact that this variant was not found to occur in 200 control chromosomes suggests that it may be pathogenic. However, overexpression of mutated PRF1 in rat basophilic leukemia cells did not affect the lytic function of perforin differently from the wild type protein