Sub-THz and THz Cherenkov radiation source with two-dimensional periodic surface lattice and multistage depressed collector.

We present the theory, concept and design of an efficient, megawatt coherent Cherenkov radiation source based on a two-dimensional periodic surface lattice (2D-PSL) cavity combined with a novel energy recovery system for the generation of highly efficient (> 50%) single-frequency radiation. We demonstrate the scalability of the transverse dimension of the 2D-PSL cavity of the Cherenkov source and thus the potential for efficient, continuous-wave, high-power (> 1 MW) operation; fundamental to the eventual realization of clean, fusion energy. These new sources, with the capacity to operate in the 0.

Outcomes following extended resection of radiation-induced angiosarcoma of the breast: a sarcoma unit experience and systematic review.

Purpose: Radiation-induced angiosarcoma (RIAS) of the breast is a rare tumour with high rate of local recurrence. The aim of this study is to evaluate the outcome of radical resections.

Methods: A retrospective analysis of all patients who underwent extended surgical resection for RIAS of the breast between 2013 and 2022.

Cross-validation of insurer and hospital price transparency data.

Given recent congressional interest in codifying price transparency regulations, it is important to understand the extent to which newly available price transparency data capture true underlying procedure-level prices. To that end, we compared the prices for maternity services negotiated between a large payer and 26 hospitals in Mississippi across 2 separate price transparency data sources: payer and hospital. The degree of file overlap is low, with only 16.

3D-SARC: A Pilot Study Testing the Use of a 3D Augmented-Reality Model with Conventional Imaging as a Preoperative Assessment Tool for Surgical Resection of Retroperitoneal Sarcoma.

Background: Retroperitoneal sarcomas (RPSs) present a surgical challenge, with complex anatomic relationships to organs and vascular structures. This pilot study investigated the role of three-dimensional (3D) augmented reality (3DAR) compared with standard imaging in preoperative planning and resection strategies.

Methods: For the study, 13 patients who underwent surgical resection of their RPS were selected based on the location of their tumor (right, left, pelvis).

Frontiers in the Application of RF Vacuum Electronics.

The application of radio frequency (RF) vacuum electronics for the betterment of the human condition began soon after the invention of the first vacuum tubes in the 1920s and has not stopped since. Today, microwave vacuum devices are powering important applications in health treatment, material and biological science, wireless communication-terrestrial and space, Earth environment remote sensing, and the promise of safe, reliable, and inexhaustible energy. This article highlights some of the exciting application frontiers of vacuum electronics.

Long-lasting memory of jasmonic acid-dependent immunity requires DNA demethylation and ARGONAUTE1.

Stress can have long-lasting impacts on plants. Here we report the long-term effects of the stress hormone jasmonic acid (JA) on the defence phenotype, transcriptome and DNA methylome of Arabidopsis. Three weeks after transient JA signalling, 5-week-old plants retained induced resistance (IR) against herbivory but showed increased susceptibility to pathogens.

Hospital And Regional Characteristics Associated With Emergency Department Facility Fee Cash Pricing.

Self-pay patients are an understudied yet important and financially vulnerable population of emergency department (ED) users. As ED facility fees may be a key cost driver in patient ED bills, we leveraged newly available hospital pricing data to describe ED facility fees for self-pay patients (cash prices) and how they vary according to hospital and regional characteristics in a sample of 1,621 hospitals across the United States. The median cash price for ED facility fees ranged from $160.

Impact of chronic lymphocytic leukaemia on melanoma outcomes: A retrospective case-control study.

With new, effective treatments for chronic lymphocytic leukaemia (CLL) the impact of second malignancies is increasingly important. We performed a retrospective case-controlled study examining the effect of CLL and its treatment on melanoma-specific survival and recurrence. A total of 56 patients with melanoma with CLL were matched 1:1 to patients without CLL for age, date of diagnosis, gender and melanoma tumour, node, metastasis (TNM) stage.

Use and outcomes of dual antiplatelet therapy for acute coronary syndrome in patients with chronic kidney disease: insights from the Canadian Observational Antiplatelet Study (COAPT).

Chronic kidney disease (CKD) increases the risk of adverse outcomes in acute coronary syndrome (ACS). The optimal regimen of dual antiplatelet therapy (DAPT) post-percutaneous coronary intervention (PCI) in CKD poses a challenge due to the increased bleeding and clotting tendencies, particularly since patients with CKD were underrepresented in randomized controlled trials. We examined the practice patterns of DAPT prescription stratified by the presence of CKD.

BRAF mutation testing for patients diagnosed with stage III or stage IV melanoma: practical guidance for the Australian setting.

Targeted therapy (BRAF inhibitor plus MEK inhibitor) is now among the possible treatment options for patients with BRAF mutation-positive stage III or stage IV melanoma. This makes prompt BRAF mutation testing an important step in the management of patients diagnosed with stage III or IV melanoma; one that can help better ensure that the optimal choice of systemic treatment is initiated with minimal delay. This article offers guidance about when and how BRAF mutation testing should be conducted when patients are diagnosed with melanoma in Australia.

A survey of surgical management of the sentinel node positive melanoma patient in the post-MSLT2 era.

Background: The evidence-based management of melanoma patients with a positive sentinel lymph node biopsy (SLNB) has undergone a dramatic shift following publication of practice-changing surgical trials demonstrating no melanoma-specific survival advantage for completion lymph node dissection (CLND) in this scenario. We aimed to survey how surgeons' clinical practice had shifted in response to new evidence from these trials, and at a time when there was starting to become available systemic adjuvant treatments for AJCC Stage III melanoma patients.

Methods: A web-based survey consisting of practice-based questions and hypothetical clinical scenarios about current melanoma practice with regard to positive sentinel node biopsy was developed and sent to the surgical members of a Melanoma and Skin Cancer (MASC) Trials group in December 2018.

MAIT cells regulate NK cell-mediated tumor immunity.

The function of MR1-restricted mucosal-associated invariant T (MAIT) cells in tumor immunity is unclear. Here we show that MAIT cell-deficient mice have enhanced NK cell-dependent control of metastatic B16F10 tumor growth relative to control mice. Analyses of this interplay in human tumor samples reveal that high expression of a MAIT cell gene signature negatively impacts the prognostic significance of NK cells.

Generating CAR T cells from tumor-infiltrating lymphocytes.

Tumor-infiltrating lymphocytes (TILs) and chimeric antigen receptor (CAR) T-cell therapies have demonstrated promising, though limited, efficacy against melanoma. We designed a model system to explore the efficacy of dual specific T cells derived from melanoma patient TILs by transduction with a Her2-specific CAR. Metastatic melanoma cells in our biobank constitutively expressed Her2 antigen.

CRISPR/Cas9 mediated deletion of the adenosine A2A receptor enhances CAR T cell efficacy.

Adenosine is an immunosuppressive factor that limits anti-tumor immunity through the suppression of multiple immune subsets including T cells via activation of the adenosine A receptor (AR). Using both murine and human chimeric antigen receptor (CAR) T cells, here we show that targeting AR with a clinically relevant CRISPR/Cas9 strategy significantly enhances their in vivo efficacy, leading to improved survival of mice. Effects evoked by CRISPR/Cas9 mediated gene deletion of AR are superior to shRNA mediated knockdown or pharmacological blockade of AR.

Insomnia in Tinnitus Patients: A Prospective Study Finding a Significant Relationship.

Tinnitus is a highly prevalent medical disorder occurring in 10-30% of the general population. This disorder often becomes chronic and severe effecting quality of life contributing to significant psychiatric consequences; one that we have written about recently is comorbid insomnia. The latter can predispose effected persons to depressive episodes and a worsening of their total functioning.

Oncologic Outcomes After Isolated Limb Infusion for Advanced Melanoma: An International Comparison of the Procedure and Outcomes Between the United States and Australia.

Background: Isolated limb infusion (ILI) is a minimally invasive procedure for delivering high-dose chemotherapy to extremities affected by locally advanced or in-transit melanoma. This study compared the outcomes of melanoma patients treated with ILI in the United States of America (USA) and Australia (AUS).

Methods: Patients with locally recurrent in-transit melanoma treated with ILI at USA or AUS centers between 1992 and 2018 were identified.

Factors predicting toxicity and response following isolated limb infusion for melanoma: An international multi-centre study.

Introduction: Isolated limb infusion (ILI) is a minimally-invasive procedure for delivering high-dose regional chemotherapy to treat melanoma in-transit metastases confined to a limb. The aim of this international multi-centre study was to identify predictive factors for toxicity and response.

Methods: Data of 687 patients who underwent a first ILI for melanoma in-transit metastases confined to the limb between 1992 and 2018 were collected at five Australian and four US tertiary referral centres.

IL-15 Preconditioning Augments CAR T Cell Responses to Checkpoint Blockade for Improved Treatment of Solid Tumors.

Chimeric antigen receptor (CAR) T cell therapy has been highly successful in hematological malignancies leading to their US Food and Drug Administration (FDA) approval. However, the efficacy of CAR T cells in solid tumors is limited by tumor-induced immunosuppression, leading to the development of combination approaches, such as adjuvant programmed cell death 1 (PD-1) blockade. Current FDA-approved methods for generating CAR T cells utilize either anti-CD3 and interleukin (IL)-2 or anti-CD3/CD28 beads, which can generate a T cell product with an effector/exhausted phenotype.

Surgical management of recurrent cutaneous squamous cell carcinoma of the head and neck after definitive surgery and radiotherapy.

Background: Surgery is the primary treatment for patients with recurrent head and neck cutaneous squamous cell carcinoma (cSCC) who have previously been treated by definitive surgery and radiotherapy. There are limited published data to direct management and the role of immunotherapy is currently under evaluation.

Methods: This was a retrospective study of patients with at least stage III recurrent head and neck cSCC previously managed by definitive surgery and radiotherapy.

Cutaneous leiomyosarcoma: dermal and subcutaneous.

Background And Objectives: Leiomyosarcoma of skin (LMS) can be sub-classified on pathology appearances as Dermal or Subcutaneous. The aim of this study was to provide treatment recommendations for these uncommon tumours.

Methods: A retrospective review of all patients with dermal and subcutaneous leiomyosarcoma managed at the Peter MacCallum Cancer Centre, Australia from January 2003 to December 2018 was performed.

Adoptive cellular therapy with T cells expressing the dendritic cell growth factor Flt3L drives epitope spreading and antitumor immunity.

Adoptive cell therapies using genetically engineered T cell receptor or chimeric antigen receptor T cells are emerging forms of immunotherapy that redirect T cells to specifically target cancer. However, tumor antigen heterogeneity remains a key challenge limiting their efficacy against solid cancers. Here, we engineered T cells to secrete the dendritic cell (DC) growth factor Fms-like tyrosine kinase 3 ligand (Flt3L).