High proportion of PD-1 and CD39 positive CD8+ tissue resident T lymphocytes correlates with better clinical outcome in resected human oesophageal adenocarcinoma.

Objective: To understand the CD8+ tumour infiltrating lymphocyte (TIL) compartment of oesophageal adenocarcinoma (OAC) with regards to markers of lymphocyte exhaustion, tissue residency and to identify possible reasons behind differential responses to therapy.

Design: Tumour samples from 44 patients undergoing curative resection for OAC were assessed by flow cytometry for presence of antigen-experienced TILs and markers of activation and exhaustion. Populations of PD-1 and CD39 positive OAC TILs were sorted, and bulk RNA sequencing undertaken using a modified SmartSeq2 protocol.

Reactivation of low avidity tumor-specific CD8 T cells associates with immunotherapeutic efficacy of anti-PD-1.

Background: CD8 T cells are a highly diverse population of cells with distinct phenotypic functions that can influence immunotherapy outcomes. Further insights on the roles of CD8 specificities and TCR avidity of naturally arising tumor-specific T cells, where both high and low avidity T cells recognizing the same peptide-major histocompatibility complex (pMHC) coexist in the same tumor, are crucial for understanding T cell exhaustion and resistance to PD-1 immunotherapy.

Methods: CT26 models were treated with anti-PD-1 on days 3, 6 and 9 following subcutaneous tumor implantation generating variable responses during early tumor development.

elearning for cancer immunotherapy.

Advances in cancer immunotherapy witnessed over the last decade with the licensing of numerous immune checkpoint inhibitors have greatly increased the application of this approach to treating advanced cancers. As a result, the number of health care professionals involved in the care of patients receiving immunotherapy treatments has grown. While the benefits can be significant, not all patients will experience them and toxicity can profound.

Subcutaneous rituximab with recombinant human hyaluronidase in the treatment of non-Hodgkin lymphoma and chronic lymphocytic leukemia.

The anti-CD20 monoclonal antibody rituximab (MabThera/Rituxan) has been proven to improve outcomes in a range of B-cell malignancies. Initially developed as a formulation for intravenous infusion, administration times for rituximab can be prolonged and associated with infusion-related reactions, prompting a combined clinical development program investigating subcutaneous delivery in combination with recombinant human hyaluronidase. As this program comes to fruition, this article reviews the evidence demonstrating subcutaneous rituximab to have noninferior pharmacokinetics when delivered at a fixed-dose as well as equivalent clinical outcomes in the treatment of follicular lymphoma, chronic lymphocytic leukemia and diffuse large B-cell lymphoma.

So much for the city: Urban-rural song variation in a widespread Asiatic songbird.

Song plays a fundamental role in intraspecific communication in songbirds. The temporal and structural components of songs can vary in different habitats. These include urban habitats where anthropogenic sounds and alteration of habitat structure can significantly affect songbird vocal behavior.

A New Electromagnetic Acoustic Transducer Design for Generating and Receiving S0 Lamb Waves in Ferromagnetic Steel Plate.

Electromagnetic acoustic transducers (EMATs) are non-contact, ultrasonic transducers that are usually kept within 5 mm from the sample surface to obtain a sufficient signal-to-noise ratio (SNR). One important issue associated with operation on a ferromagnetic plate is that the strong attraction force from the magnet can affect measurements and make scanning difficult. This paper investigates a method to generate fundamental, symmetric Lamb waves on a ferromagnetic plate.

Plasmonic photothermal heating of intraperitoneal tumors through the use of an implanted near-infrared source.

Plasmonic nanomaterials including gold nanorods are effective agents for inducing heating in tumors. Because near-infrared (NIR) light has traditionally been delivered using extracorporeal sources, most applications of plasmonic photothermal therapy have focused on isolated subcutaneous tumors. For more complex models of disease such as advanced ovarian cancer, one of the primary barriers to gold nanorod-based strategies is the adequate delivery of NIR light to tumors located at varying depths within the body.

The wave-field from an array of periodic emitters driven simultaneously by a broadband pulse.

The use of phased array methods are commonplace in ultrasonic applications, where controlling the variation of the phase between the narrowband emitters in an array facilitates beam steering and focusing of ultrasonic waves. An approach is presented here whereby emitters of alternating polarity arranged in a one-dimensional array are pulsed simultaneously, and have sufficiently wide, controlled bandwidth to emit a two-dimensional wave. This pulsed approach provides a rapid means of simultaneously covering a region of space with a wave-front, whereby any wave that scatters or reflects off a body to a detector will have a distinct arrival time and frequency.

Gender differences in hepatitis C seroprevalence and suboptimal vaccination and hepatology services uptake amongst substance misusers.

Injecting drug users are the principal at risk group for blood borne viruses. The aim was to assess the feasibility of screening substance misusers for blood borne viruses, and to offer appropriate vaccinations/referral to hepatology services. This was a nurse led prospective 6-month study based at a large Substance Misuse Service in south east England.

Endogenous opioid release in the human brain reward system induced by acute amphetamine administration.

Background: We aimed to demonstrate a pharmacologically stimulated endogenous opioid release in the living human brain by evaluating the effects of amphetamine administration on [(11)C]carfentanil binding with positron emission tomography (PET).

Methods: Twelve healthy male volunteers underwent [(11)C]carfentanil PET before and 3 hours after a single oral dose of d-amphetamine (either a "high" dose, .5 mg/kg, or a sub-pharmacological "ultra-low" dose, 1.

Automated preparation of the dopamine D2/3 receptor agonist ligand [11C]-(+)-PHNO for human PET imaging studies.

Carbon-11 labelled (+)-4-Propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol ([(11)C]-(+)-PHNO) is used as a high-affinity state, dopamine D(2/3) receptor ligand in clinical PET studies. To facilitate its use, robust, rapid, efficient and GMP compliant methods are required for the manufacturing and QC testing processes. Additionally, to allow for full quantification of the resulting signal in the CNS, a reliable method is required to establish the parent plasma concentration over the course of the scan.

Occlusion-capable multiview volumetric three-dimensional display.

Volumetric 3D displays are frequently purported to lack the ability to reconstruct scenes with viewer-position-dependent effects such as occlusion. To counter these claims, a swept-screen 198-view horizontal-parallax-only 3D display is reported here that is capable of viewer-position-dependent effects. A digital projector illuminates a rotating vertical diffuser with a series of multiperspective 768 x 768 pixel renderings of a 3D scene.

Long-term follow-up after gentamicin application via the Silverstein MicroWick in the treatment of Ménière's disease.

We conducted a retrospective study to evaluate the long-term effectiveness of gentamicin applied directly to the round window membrane via the Silverstein MicroWick system in patients with definite or probable Ménière's disease. The study population was made up of 69 patients who had received 3 drops of gentamicin 10 mg/ml three times daily; the duration of treatment was guided by objective data obtained from weekly electronystagmography and audiometry. Relief of vertigo was assessed by chart review and telephone interviews.

Assessment of patient satisfaction with various configurations of digital CROS and BiCROS hearing aids.

We conducted a study of 91 patients with severe-to-profound asymmetric hearing loss to assess their satisfaction with digital contralateral routing of signal (CROS) or bilateral contralateral routing of signal (BiCROS) hearing aids, Satisfaction was evaluated on the basis of the number of patients who elected to purchase their hearing aid following a free 30-day trial and on the results of a subsequent 8-question survey. We found that overall patient satisfaction was generally high. At the end of the 30-day trial, 66 of the 91 patients (72.

Swallowing function outcomes following nonsurgical therapy for advanced-stage laryngeal carcinoma.

The purposes of this study were to (1) evaluate swallowing function using both subjective and objective measures in patients treated nonsurgically for stages III and IV laryngeal squamous cell carcinoma, (2) assess the effect of time from treatment completion on swallowing function, and (3) assess sequelae associated with modality of treatment. To achieve these objectives, a retrospective study of 14 patients was conducted. Fiberoptic endoscopic evaluation of swallowing (FEES) was performed and evaluated by three independent judges for seven functional criteria: standing secretions, valleculae spillage, valleculae residue, postcricoid residue, laryngeal penetration, aspiration, and cough.

The effects of montelukast on intradermal wheal and flare.

Objective: We sought to determine the effect of montelukast, a leukotriene receptor antagonist, on intradermal skin testing. Study design and setting We conducted a prospective, randomized, double-blind, placebo-controlled study in a university setting.

Methods: After a 1-week washout of allergy pharmacotherapy, intradermal skin testing was performed on 23 atopic subjects.

Functional outcomes following nonsurgical treatment for advanced-stage laryngeal carcinoma.

Objectives: Objectives were 1) to provide comprehensive evaluations of functional outcomes using perceptual and objective measures of patients treated nonsurgically for stages III and IV laryngeal squamous cell carcinoma and 2) to propose a standard battery of tests that can be used for appraising functional outcomes in this patient population.

Study Design: Retrospective study of 14 patients.

Methods: Perceptual measures of voice were obtained using blinded expert listener impression ratings and a validated quality of life questionnaire (Voice Handicap Index).