EGFR-specific T cell frequencies correlate with EGFR expression in head and neck squamous cell carcinoma

Background\ud In head and neck squamous cell carcinoma (HNSCC), expression levels of the epidermal growth factor receptor (EGFR) correlate with poor prognosis and decreased survival rates. As the mechanisms responsible for cellular immune response to EGFR in vivo remain unclear, the frequency and function of EGFR-specific cytotoxic T cells (CTL) was determined in HNSCC patients.\ud \ud Methods\ud The frequency of CTL specific for the HLA-A2.1-restricted EGFR-derived YLN peptide (YLNTVQPTCV) and KLF peptide (KLFGTSGQKT) was determined in 16 HLA-A2.1+ HNSCC patients and 16 healthy HLA-A2.1+ individuals (NC) by multicolor flow cytometry. Patients' results were correlated to EGFR expression obtained by immunohistochemistry in corresponding tumor sections. Proliferation and anti-tumor activity of peptide-specific CTL was demonstrated by in vitro stimulation with dendritic cells pulsed with the peptides.\ud \ud Results\ud Frequency of EGFR-specific CTL correlated significantly with EGFR expression in tumor sections (p = 0.02, r2 = 0.6). Patients with elevated EGFR scores (> 7) had a significantly higher frequency of EGFR-specific CTL than NC and patients with low EGFR scores (< 7). EGFR-specific CTL from cancer patients were expanded ex vivo and produced IFN-γ upon recognition of EGFR+ target cells.\ud \ud Conclusion\ud EGFR expressed on HNSCC cells induces a specific immune response in vivo. Strategies for expansion of EGFR-specific CTL may be important for future immunotherapy of HNSCC patients

A systematic review of the evidence for single stage and two stage revision of infected knee replacement

BACKGROUND: Periprosthetic infection about the knee is a devastating complication that may affect between 1% and 5% of knee replacement. With over 79 000 knee replacements being implanted each year in the UK, periprosthetic infection (PJI) is set to become an important burden of disease and cost to the healthcare economy. One of the important controversies in treatment of PJI is whether a single stage revision operation is superior to a two-stage procedure. This study sought to systematically evaluate the published evidence to determine which technique had lowest reinfection rates. METHODS: A systematic review of the literature was undertaken using the MEDLINE and EMBASE databases with the aim to identify existing studies that present the outcomes of each surgical technique. Reinfection rate was the primary outcome measure. Studies of specific subsets of patients such as resistant organisms were excluded. RESULTS: 63 studies were identified that met the inclusion criteria. The majority of which (58) were reports of two-stage revision. Reinfection rated varied between 0% and 41% in two-stage studies, and 0% and 11% in single stage studies. No clinical trials were identified and the majority of studies were observational studies. CONCLUSIONS: Evidence for both one-stage and two-stage revision is largely of low quality. The evidence basis for two-stage revision is significantly larger, and further work into direct comparison between the two techniques should be undertaken as a priority

Site-specific prolapse surgery. I. Reliability and durability of native tissue paravaginal repair

Introduction and hypothesis: This study aims to compare native tissue abdominal and vaginal paravaginal repair, and to investigate whether surgical outcome was independent of operative route. Methods: Retrospective comparison of 111 displacement cysto-urethrocoeles, repaired between 1997 and 2007. Treatment was by surgeon assignment, 52 women having abdominal (APVR) and 59 vaginal paravaginal repairs. Main outcome measures were same-site prolapse recurrence, time to failure and surgical complications. Initial reliability was evaluated by chi-square test, 10-year durability by Kaplan-Meier survival analysis and Cox proportional hazards model. Results: When examined in the Cox proportional hazards model, anatomic results of APVR were more durable than a mechanically analogous transvaginal operation done [95% CI=1.029-2.708 (p value=0.038)]. Kaplan-Meier curves plateaued within 38 months. Symptom resolution was broadly equivalent. Surgical complication rate was 3.6%. Conclusions: Site-specific re-suture of torn native tissue has genuine curative potential. Most of the long-term success was attributable to site-specific repair, rather than nonspecific scar formation.9 page(s

Geographic range did not confer resilience to extinction in terrestrial vertebrates at the end-Triassic crisis

Rates of extinction vary greatly through geological time, with losses particularly concentrated in mass extinctions. Species duration at other times varies greatly, but the reasons for this are unclear. Geographical range correlates with lineage duration amongst marine invertebrates, but it is less clear how far this generality extends to other groups in other habitats. It is also unclear whether a wide geographical distribution makes groups more likely to survive mass extinctions. Here we test for extinction selectivity amongst terrestrial vertebrates across the end-Triassic event. We demonstrate that terrestrial vertebrate clades with larger geographical ranges were more resilient to extinction than those with smaller ranges throughout the Triassic and Jurassic. However, this relationship weakened with increasing proximity to the end-Triassic mass extinction, breaking down altogether across the event itself. We demonstrate that these findings are not a function of sampling biases; a perennial issue in studies of this kind

Preconceptional Folate Supplementation and the Risk of Spontaneous Preterm Birth: A Cohort Study

In an analysis of a cohort of pregnant women, Radek Bukowski and colleagues describe an association between taking folic acid supplements and a reduction in the risk of preterm birth

Status report on emerging photovoltaics

\ua9 2023 Society of Photo-Optical Instrumentation Engineers (SPIE).This report provides a snapshot of emerging photovoltaic (PV) technologies. It consists of concise contributions from experts in a wide range of fields including silicon, thin film, III-V, perovskite, organic, and dye-sensitized PVs. Strategies for exceeding the detailed balance limit and for light managing are presented, followed by a section detailing key applications and commercialization pathways. A section on sustainability then discusses the need for minimization of the environmental footprint in PV manufacturing and recycling. The report concludes with a perspective based on broad survey questions presented to the contributing authors regarding the needs and future evolution of PV

Identification of the Regulatory Logic Controlling Salmonella Pathoadaptation by the SsrA-SsrB Two-Component System

Sequence data from the past decade has laid bare the significance of horizontal gene transfer in creating genetic diversity in the bacterial world. Regulatory evolution, in which non-coding DNA is mutated to create new regulatory nodes, also contributes to this diversity to allow niche adaptation and the evolution of pathogenesis. To survive in the host environment, Salmonella enterica uses a type III secretion system and effector proteins, which are activated by the SsrA-SsrB two-component system in response to the host environment. To better understand the phenomenon of regulatory evolution in S. enterica, we defined the SsrB regulon and asked how this transcription factor interacts with the cis-regulatory region of target genes. Using ChIP-on-chip, cDNA hybridization, and comparative genomics analyses, we describe the SsrB-dependent regulon of ancestral and horizontally acquired genes. Further, we used a genetic screen and computational analyses integrating experimental data from S. enterica and sequence data from an orthologous regulatory system in the insect endosymbiont, Sodalis glossinidius, to identify the conserved yet flexible palindrome sequence that defines DNA recognition by SsrB. Mutational analysis of a representative promoter validated this palindrome as the minimal architecture needed for regulatory input by SsrB. These data provide a high-resolution map of a regulatory network and the underlying logic enabling pathogen adaptation to a host

Unpacking the relationships between impulsivity, neighborhood disadvantage, and adolescent violence : an application of a neighborhood-based group decomposition

The research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP/2007–2013)/ERC Grant Agreement no. 615159 (ERC Consolidator Grant DEPRIVEDHOODS, Socio-spatial inequality, deprived neighbourhoods, and neighbourhood effects); and from the Marie Curie programme under the European Union’s Seventh Framework Programme (FP/2007–2013)/Career Integration Grant no. PCIG10-GA-2011-303728 (CIG Grant NBHCHOICE, Neighbourhood choice, neighbourhood sorting, and neighbourhood effects).Scholars have become increasingly interested in how social environments condition the relationships between individual risk-factors and adolescent behavior. An appreciable portion of this literature is concerned with the relationship between impulsivity and delinquency across neighborhood settings. The present article builds upon this growing body of research by considering the more nuanced pathways through which neighborhood disadvantage shapes the development of impulsivity and provides a situational context for impulsive tendencies to manifest in violent and aggressive behaviors. Using a sample of 12,935 adolescent from the National Longitudinal Study of Adolescent to Adult Health (Add Health) (mean age = 15.3, 51% female; 20% Black, 17% Hispanic), we demonstrate the extent to which variation in the association between impulsivity and delinquency across neighborhoods can be attributed to (1) differences in mean-levels of impulsivity and violence and (2) differences in coefficients across neighborhoods. The results of a series of multivariate regression models indicate that impulsivity is positively associated with self-reported violence, and that this relationship is strongest among youth living in disadvantaged neighborhoods. The moderating effect of neighborhood disadvantage can be attributed primarily to the stronger effect of impulsivity on violence in these areas, while differences in average levels of violence and impulsivity account for a smaller, yet nontrivial portion of the observed relationship. These results indicate that the differential effect of impulsivity on violence can be attributed to both developmental processes that lead to the greater concentration of violent and impulsive adolescents in economically deprived neighborhoods as well as the greater likelihood of impulsive adolescents engaging in violence when they reside in economically disadvantaged communities.Publisher PDFPeer reviewe

Genomic profiling identifies common HPV-associated chromosomal alterations in squamous cell carcinomas of cervix and head and neck

<p>Abstract</p> <p>Background</p> <p>It is well known that a persistent infection with high-risk human papillomavirus (hrHPV) is causally involved in the development of squamous cell carcinomas of the uterine cervix (CxSCCs) and a subset of SCCs of the head and neck (HNSCCs). The latter differ from hrHPV-negative HNSCCs at the clinical and molecular level.</p> <p>Methods</p> <p>To determine whether hrHPV-associated SCCs arising from different organs have specific chromosomal alterations in common, we compared genome-wide chromosomal profiles of 10 CxSCCs (all hrHPV-positive) with 12 hrHPV-positive HNSCCs and 30 hrHPV-negative HNSCCs. Potential organ-specific alterations and alterations shared by SCCs in general were investigated as well.</p> <p>Results</p> <p>Unsupervised hierarchical clustering resulted in one mainly hrHPV-positive and one mainly hrHPV-negative cluster. Interestingly, loss at 13q and gain at 20q were frequent in HPV-positive carcinomas of both origins, but uncommon in hrHPV-negative HNSCCs, indicating that these alterations are associated with hrHPV-mediated carcinogenesis. Within the group of hrHPV-positive carcinomas, HNSCCs more frequently showed gains of multiple regions at 8q whereas CxSCCs more often showed loss at 17p. Finally, gains at 3q24-29 and losses at 11q22.3-25 were frequent (>50%) in all sample groups.</p> <p>Conclusion</p> <p>In this study hrHPV-specific, organ-specific, and pan-SCC chromosomal alterations were identified. The existence of hrHPV-specific alterations in SCCs of different anatomical origin, suggests that these alterations are crucial for hrHPV-mediated carcinogenesis.</p