Pathologist Concordance for Ovarian Carcinoma Subtype Classification and Identification of Relevant Histologic Features Using Microscope and Whole Slide Imaging.

CONTEXT.—: Despite several studies focusing on the validation of whole slide imaging (WSI) across organ systems or subspecialties, the use of WSI for specific primary diagnosis tasks has been underexamined. OBJECTIVE.—: To assess pathologist performance for the histologic subtyping of individual sections of ovarian carcinomas using a light microscope and WSI. DESIGN.—: A panel of 3 experienced gynecologic pathologists provided reference subtype diagnoses for 212 histologic sections from 109 ovarian carcinomas based on optical microscopy review. Two additional attending pathologists provided diagnoses and also identified the presence of a set of 8 histologic features important for ovarian tumor subtyping. Two experienced gynecologic pathologists and 2 fellows reviewed the corresponding WSI images for subtype classification and feature identification. RESULTS.—: Across pathologists specialized in gynecologic pathology, concordance with the reference diagnosis for the 5 major ovarian carcinoma subtypes was significantly higher for a pathologist reading on a microscope than each of 2 pathologists reading on WSI. Differences were primarily due to more frequent classification of mucinous carcinomas as endometrioid with WSI. Pathologists had generally low agreement in identifying histologic features important to ovarian tumor subtype classification with either an optical microscopy or WSI. This result suggests the need for refined histologic criteria for identifying such features. Interobserver agreement was particularly low for identifying intracytoplasmic mucin with WSI. Inconsistencies in evaluating nuclear atypia and mitoses with WSI were also observed. CONCLUSIONS.—: Further research is needed to specify the reasons for these diagnostic challenges and to inform users and manufacturers of WSI technology

Impurity-induced stabilization of solitons in arrays of parametrically driven nonlinear oscillators

Chains of parametrically driven, damped pendula are known to support soliton-like clusters of in-phase motion which become unstable and seed spatiotemporal chaos for sufficiently large driving amplitudes. We show that the pinning of the soliton on a "long" impurity (a longer pendulum) expands dramatically its stability region whereas "short" defects simply repel solitons producing effective partition of the chain. We also show that defects may spontaneously nucleate solitons.Comment: 4 pages in RevTeX; 7 figures in ps forma

Locking bandwidth of two laterally coupled semiconductor lasers subject to optical injection

We report here for the first time (to our knowledge), a new and universal mechanism by which a two-element laser array is locked to external optical injection and admits stably injection-locked states within a nontrivial trapezoidal region. The rate equations for the system are studied both analytically and numerically. We derive a simple mathematical expression for the locking conditions, which reveals that two parallel saddle-node bifurcation branches, not reported for conventional single lasers subject to optical injection, delimit the injection locking range and its width. Important parameters are the linewidth enhancement factor, the laser separation, and the frequency offset between the two laterally-coupled lasers; the influence of these parameters on locking conditions is explored comprehensively. Our analytic approximations are validated numerically by using a path continuation technique as well as direct numerical integration of the rate equations. More importantly, our results are not restricted by waveguiding structures and uncover a generic locking behavior in the lateral arrays in the presence of injection

Functional immune responses against SARS-CoV-2 variants of concern after fourth COVID-19 vaccine dose or infection in patients with blood cancer

Patients with blood cancer continue to have a greater risk of inadequate immune responses following three COVID-19 vaccine doses and risk of severe COVID-19 disease. In the context of the CAPTURE study (NCT03226886), we report immune responses in 80 patients with blood cancer who received a fourth dose of BNT162b2. We measured neutralizing antibody titers (NAbTs) using a live virus microneutralization assay against wild-type (WT), Delta, and Omicron BA.1 and BA.2 and T cell responses against WT and Omicron BA.1 using an activation-induced marker (AIM) assay. The proportion of patients with detectable NAb titers and T cell responses after the fourth vaccine dose increased compared with that after the third vaccine dose. Patients who received B cell-depleting therapies within the 12 months before vaccination have the greatest risk of not having detectable NAbT. In addition, we report immune responses in 57 patients with breakthrough infections after vaccination

Adaptive immunity and neutralizing antibodies against SARS-CoV-2 variants of concern following vaccination in patients with cancer: the CAPTURE study

Coronavirus disease 2019 (COVID-19) antiviral response in a pan-tumor immune monitoring (CAPTURE) (NCT03226886) is a prospective cohort study of COVID-19 immunity in patients with cancer. Here we evaluated 585 patients following administration of two doses of BNT162b2 or AZD1222 vaccines, administered 12 weeks apart. Seroconversion rates after two doses were 85% and 59% in patients with solid and hematological malignancies, respectively. A lower proportion of patients had detectable titers of neutralizing antibodies (NAbT) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) versus wild-type (WT) SARS-CoV-2. Patients with hematological malignancies were more likely to have undetectable NAbT and had lower median NAbT than those with solid cancers against both SARS-CoV-2 WT and VOC. By comparison with individuals without cancer, patients with hematological, but not solid, malignancies had reduced neutralizing antibody (NAb) responses. Seroconversion showed poor concordance with NAbT against VOC. Previous SARS-CoV-2 infection boosted the NAb response including against VOC, and anti-CD20 treatment was associated with undetectable NAbT. Vaccine-induced T cell responses were detected in 80% of patients and were comparable between vaccines or cancer types. Our results have implications for the management of patients with cancer during the ongoing COVID-19 pandemic

Functional antibody and T cell immunity following SARS-CoV-2 infection, including by variants of concern, in patients with cancer: the CAPTURE study

Patients with cancer have higher COVID-19 morbidity and mortality. Here we present the prospective CAPTURE study, integrating longitudinal immune profiling with clinical annotation. Of 357 patients with cancer, 118 were SARS-CoV-2 positive, 94 were symptomatic and 2 died of COVID-19. In this cohort, 83% patients had S1-reactive antibodies and 82% had neutralizing antibodies against wild type SARS-CoV-2, whereas neutralizing antibody titers against the Alpha, Beta and Delta variants were substantially reduced. S1-reactive antibody levels decreased in 13% of patients, whereas neutralizing antibody titers remained stable for up to 329 days. Patients also had detectable SARS-CoV-2-specific T cells and CD4+ responses correlating with S1-reactive antibody levels, although patients with hematological malignancies had impaired immune responses that were disease and treatment specific, but presented compensatory cellular responses, further supported by clinical recovery in all but one patient. Overall, these findings advance the understanding of the nature and duration of the immune response to SARS-CoV-2 in patients with cancer

Neutralising antibodies after COVID-19 vaccination in UK haemodialysis patients

Vaccination against COVID-19 induces highly protective immune responses in most people. As some countries switch from suppression to acceptance of transmission of SARS-CoV-2 within a largely vaccinated adult population, vulnerable patient groups that have not mounted adequate immune responses to vaccination might experience significant morbidity and mortality. There is an urgent need to identify such patient groups and to optimise medical advice and vaccination strategies for them

A faithful compass: rethinking the term restorative justice to find clarity

In the field of restorative justice (rj) there is regular debate regarding the terms restorative and justice. In spite of efforts to come to a common vision, this ongoing discussion illustrates how theoretical and practical disagreements have resulted in rj being characterized as ambiguous and inconsistent within the judicial context and beyond (Gavrielides, 2008; Sullivan & Tifft, 2005; Johnstone & Van Ness, 2007). Arising out of research conducted in an education context (Vaandering, 2009), this paper identifies the impact of this ambiguity on educators. More importantly, however, it examines the term justice and discovers that an overemphasis on justice as fairness and individual rights has pulled the field off-course. The paper identifies that what is needed is a broader understanding of justice than that given in the judicial context and makes the case for justice as honouring the inherent worth of all and enacted through relationship. If understood as such, I argue that the terms restorative and justice must remain paired and in place in order to serve as a muchneeded compass needle that guides proponents of rj in the field to their desired destinations