Fully Differentiated HIV-1 Specific CD8+ T Effector Cells are More Frequently Detectable in Controlled than in Progressive HIV-1 Infection

Background: CD8+ T cells impact control of viral infections by direct elimination of infected cells and secretion of a number of soluble factors. In HIV-1 infection, persistent HIV-1 specific IFN-γ+ CD8+ T cell responses are detected in the setting of disease progression, consistent with functional impairment in vivo. Recent data suggest that impaired maturation, as defined by the lineage markers CD45RA and CCR7, may contribute to a lack of immune control by these responses. Methodology/Principal Findings: We investigated the maturation phenotype of epitope-specific CD8+ T cell responses directed against HIV-1 in 42 chronically infected, untreated individuals, 22 of whom were “Controllers” (median 1140 RNA copies/ml plasma, range less than 50 to 2520), and 20 “progressors” of whom had advanced disease and high viral loads (median 135,500 RNA copies/ml plasma, range 12100 to greater than 750000). Evaluation of a mean of 5 epitopes per person revealed that terminally differentiated CD8+ T cells directed against HIV-1 are more often seen in HIV-1 Controllers (16/22; 73%) compared to HIV-1 progressors (7/20; 35%)(p = 0.015), but the maturation state of epitope-specific responses within a given individual was quite variable. Maturation phenotype was independent of the HLA restriction or the specificity of a given CD8+ T cell response and individual epitopes associated with slow disease progression were not more likely to be terminally differentiated. Conclusions/Significance: These data indicate that although full maturation of epitope-specific CD8+ T cell responses is associated with viral control, the maturation status of HIV-1 specific CD8+ T cell responses within a given individual are quite heterogeneous, suggesting epitope-specific influences on CD8+ T cell function

Gas Permeability of Plantation Loblolly Pine

Gas permeability of loblolly pine sapwood was determined for samples from six plantation-grown trees. Longitudinal permeability measurements were made on wood from five heights in the trees, juvenile and mature wood, and earlywood and latewood. Samples were either solvent-dried to obtain a green-equivalent state or air-dried. Permeability was also measured in the tangential and radial directions. Longitudinal permeability was significantly less in the lower part of the tree than in the upper part. Mature wood was more permeable than juvenile wood for both green-equivalent and air-dried wood as well as earlywood and latewood. Permeability did not appear to be solely a function of specific gravity

Acoustic Sorting Models for Improved Log Segregation

In this study, we examined three individual log measures (acoustic velocity, log diameter, and log vertical position in a tree) for their ability to predict average modulus of elasticity (MOE) and grade yield of structural lumber obtained from Douglas-fir (Pseudotsuga menziesii [Mirb. Franco]) logs. We found that log acoustic velocity only had a moderate correlation with average MOE of the lumber produced from the logs (R2 = 0.40). Log diameter had a weak correlation with average lumber MOE (R2 = 0.12). Log vertical position in a tree was found to have a relatively good relationship with lumber MOE (R2 = 0.57). Our analysis also indicated that the combinations of log acoustic velocity and log diameter or log acoustic velocity and log position were better predictors of average lumber MOE and lumber visual grade yield than log acoustic velocity alone. For sorting best quality logs, multivariable models were more effective than the velocity-alone model; however, for sorting poorest quality logs, the velocity-alone model was as effective as multivariable models

Utility of commonly used commercial human chorionic gonadotropin immunoassays in the diagnosis and management of trophoblastic diseases.

A multi-centre study involving worldwide collaboration highlighted the between-method variation in hCG quantification and estimation and the resultant potential misdiagnosis of GTD

Tumour seeding in the tract of percutaneous renal tumour biopsy: A report on seven cases from a UK tertiary referral centre

The role of percutaneous renal tumour biopsy (RTB) in the management of radiological indeterminate renal masses is long established. Patients with small renal masses who have biopsy-proven renal cell carcinoma (RCC) may be offered surgery, ablative therapy, or active surveillance, and RTB can provide diagnostic tissue from patients with metastatic disease who might benefit from systemic therapy. Current guidelines suggest that tumour seeding along the needle tract is anecdotal, but several cases have been reported recently, although some have been associated with lack of a coaxial sheath. We report on seven patients who underwent surgical resection of RCC in our tertiary referral institution following diagnostic RTB between 2014 and 2017 for whom RTB tract seeding by tumour was identified on histological examination of the resection specimen. One of these patients subsequently developed local tumour recurrence at the site of the previous biopsy

Active Monitoring, Surgery, and Radiotherapy for Cribriform-Positive and Cribriform-Negative Prostate Cancer:A Secondary Analysis of the PROTECT Randomized Clinical Trial

Importance Cribriform prostate cancer is associated with poor outcomes; however, its optimal treatment strategy remains unclear in the absence of randomized data.Objective To retrospectively analyze the results of the PROTECT randomized clinical trial to establish the association between cribriform-positive and cribriform-negative prostate cancer and 15-year risk of metastasis in patients who underwent active monitoring, surgery, or radiotherapy.Design, Setting, and Participants Between 1999 and 2009, the PROTECT phase 3 randomized clinical trial enrolled 1643 men with clinically localized prostate cancer who were randomly assigned to receive active monitoring, surgery, or radiotherapy with neoadjuvant androgen deprivation therapy (ADT). In this secondary analysis of the PROTECT trial, a centralized histopathologic review was conducted on available diagnostic biopsy slides to classify patients as cribriform-positive if they had invasive cribriform carcinoma and/or intraductal carcinoma. Data were collected from January 25, 2024, to October 11, 2024, and were analyzed from October 14, 2024, to January 30, 2025.Exposures Age, prostate-specific antigen (PSA), Gleason score, and cribriform status.Main Outcomes and Measures The primary outcome was progression to metastatic disease (bony, visceral, or lymph node metastases on imaging or PSA >100 ng/mL). Multivariable Cox proportional hazards regression models, adjusted for randomization variables, were incorporated to assess 15-year metastasis risk. Cumulative incidence curves were compared using the Gray test. Both intention-to-treat and per-protocol analyses were performed.Results Among 712 men (mean [SD] age, 62.0 [5.0] years) whose biopsies were retrospectively reviewed, 93 (13.1%) had cribriform-positive disease and 42 (5.9%) developed metastasis. In the intention-to-treat cohort, cribriform-positive disease significantly increased the risk of metastasis (hazard ratio [HR], 3.61 [95% CI, 1.60-8.11]; P = .003). Radiotherapy with neoadjuvant ADT significantly reduced metastasis risk (HR, 0.35 [95% CI, 0.16-0.78]; P = .04) (15-year cumulative incidence in patients with cribriform-positive disease, 8%), while surgery delayed metastasis but did not significantly improve long-term outcomes compared with active monitoring (HR, 0.52 [95% CI, 0.25-1.08]; P = .09) (15-year cumulative incidence in patients with cribriform-positive disease, 26% for surgery and 25% for active monitoring). Among patients with cribriform-negative disease, incidence of metastasis was low and did not differ by treatment. Similar per-protocol results were noted.Conclusions and Relevance The findings of this secondary analysis of the PROTECT randomized clinical trial suggest that cribriform morphology was a strong, independent predictor of 15-year metastasis among patients with prostate cancer and that radiotherapy with neoadjuvant ADT was associated with a reduced long-term risk of metastasis. Conversely, outcomes were favorable for most patients with cribriform-negative disease, supporting their eligibility for active surveillance.Trial Registration ClinicalTrials.gov Identifier: NCT0204417

Pathology and regulation for research in the UK: An overview [version 2; peer review: 3 approved]

The input of pathologists is essential for the conduct of many forms of research, including clinical trials. As the custodians of patient samples, pathology departments have a duty to ensure compliance with the relevant regulations, standards and guidelines to ensure the ethical and effective use for their intended investigational analysis, including when patients are participating in a research study. The results of research studies have impacts beyond the research study itself as they may inform changes in policy and practice or support the licensing of medicines and devices. Compliance with regulations and standards provides public assurance that the rights, safety and wellbeing of research participants are protected, that the data have been collected and processed to ensure their integrity and that the research will achieve its purpose. The requirements of the regulatory environment should not be seen as a barrier to research and should not significantly impact on the work of the laboratory once established and integrated into practice. This paper highlights important regulations, policy, standards and available guidance documents that apply to research involving NHS pathology departments and academic laboratories that are contributing to research involving human subjects

Pathology and regulation for research in the UK: An overview [version 2; peer review: 3 approved]

The input of pathologists is essential for the conduct of many forms of research, including clinical trials. As the custodians of patient samples, pathology departments have a duty to ensure compliance with the relevant regulations, standards and guidelines to ensure the ethical and effective use for their intended investigational analysis, including when patients are participating in a research study. The results of research studies have impacts beyond the research study itself as they may inform changes in policy and practice or support the licensing of medicines and devices. Compliance with regulations and standards provides public assurance that the rights, safety and wellbeing of research participants are protected, that the data have been collected and processed to ensure their integrity and that the research will achieve its purpose. The requirements of the regulatory environment should not be seen as a barrier to research and should not significantly impact on the work of the laboratory once established and integrated into practice. This paper highlights important regulations, policy, standards and available guidance documents that apply to research involving NHS pathology departments and academic laboratories that are contributing to research involving human subjects