A Scanned Perturbation Technique For Imaging Electromagnetic Standing Wave Patterns of Microwave Cavities

We have developed a method to measure the electric field standing wave distributions in a microwave resonator using a scanned perturbation technique. Fast and reliable solutions to the Helmholtz equation (and to the Schrodinger equation for two dimensional systems) with arbitrarily-shaped boundaries are obtained. We use a pin perturbation to image primarily the microwave electric field amplitude, and we demonstrate the ability to image broken time-reversal symmetry standing wave patterns produced with a magnetized ferrite in the cavity. The whole cavity, including areas very close to the walls, can be imaged using this technique with high spatial resolution over a broad range of frequencies.Comment: To be published in Review of Scientific Instruments,September, 199

Practical considerations in screening for genetic alterations in cholangiocarcinoma

Cholangiocarcinoma (CCA) encompasses diverse epithelial tumors historically associated with poor outcomes due to an aggressive disease course, late diagnosis, and limited benefit of standard chemotherapy for advanced disease. Comprehensive molecular profiling has revealed a diverse landscape of genomic alterations as oncogenic drivers in CCA. TP53 mutations, CDKN2A/B loss, and KRAS mutations are the most common genetic alterations in CCA. However, intrahepatic CCA (iCCA) and extrahepatic CCA (eCCA) differ substantially in the frequency of many alterations. This includes actionable alterations, such as IDH1 mutations and a large variety of FGFR2 rearrangements, which are found in up to 29% and approximately 10% of patients with iCCA, respectively, but are rare in eCCA. FGFR2 rearrangements are currently the only genetic alteration in CCA for which a targeted therapy, the FGFR1-3 inhibitor pemigatinib, has been approved. However, favorable phase 3 results for IDH1-targeted therapy with ivosidenib in iCCA have been published, and numerous other alterations are actionable by targeted therapies approved in other indications. Recent advances in next-generation sequencing (NGS) have led to the development of assays that allow comprehensive genomic profiling of large gene panels within 2-3 weeks, including in vitro diagnostic tests approved in the US. These assays vary regarding acceptable source material (tumor tissue or peripheral whole blood), genetic source for library construction (DNA or RNA), target selection technology, gene panel size, and type of detectable genomic alterations. While some large commercial laboratories offer rapid and comprehensive genomic profiling services based on proprietary assay platforms, clinical centers may use commercial genomic profiling kits designed for clinical research to develop their own customized laboratory-developed tests. Large-scale genomic profiling based on NGS allows for a detailed and precise molecular diagnosis of CCA and provides an important opportunity for improved targeted treatment plans tailored to the individual patient’s genetic signature

Systemic therapies for intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma (iCCA) is a highly lethal hepatobiliary neoplasm whose incidence is increasing. Largely neglected for decades as a rare malignancy and frequently misdiagnosed as carcinoma of unknown primary, considerable clinical and investigative attention has recently been focused on iCCA worldwide. The established standard of care includes first-line (gemcitabine and cisplatin), second-line (FOLFOX) and adjuvant (capecitabine) systemic chemotherapy. Compared to hepatocellular carcinoma, iCCA is genetically distinct with several targetable genetic aberrations identified to date. Indeed, FGFR2 and NTRK fusions, and IDH1 and BRAF targetable mutations have been comprehensively characterised and clinical data is emerging on targeting these oncogenic drivers pharmacologically. Also, the role of immunotherapy has been examined and is an area of intense investigation. Herein, in a timely and topical manner, we will review these advances and highlight future directions of research

Targeting FGFR inhibition in cholangiocarcinoma

Cholangiocarcinomas (CCAs) are rare but aggressive tumours of the bile ducts, which are often diagnosed at an advanced stage and have poor outcomes on systemic therapy. Somatic alterations with therapeutic implications have been identified in almost half of CCAs, in particular in intrahepatic CCA (iCCA), the subtype arising from bile ducts within the liver. Among patients with CCA, fibroblast growth factor receptor 2 (FGFR2) fusions or rearrangements occur almost exclusively in iCCA, where they are estimated to be found in up to 10–15% of patients. Clinical trials for selective FGFR kinase inhibitors have shown consistent activity of these agents in previously treated patients with iCCA harbouring FGFR alterations. Current FGFR kinase inhibitors show differences in their structure, mechanisms of target engagement, and specificities for FGFR1, 2, 3 and 4 and other related kinases. These agents offer the potential to improve outcomes in FGFR-driven CCA, and the impact of variations in the molecular profiles of the FGFR inhibitors on efficacy, safety, acquired resistance mechanisms, and patients’ health-related quality of life remains to be fully characterized. The most common adverse event associated with FGFR inhibitors is hyperphosphatemia, an on-target off-tumour effect of FGFR1 inhibition, and strategies to manage this include dose adjustment, chelators, and the use of a low phosphate diet. As FGFR inhibitors and other targeted agents enter the clinic for use in FGFR-driven CCA, molecular testing for actionable mutations and monitoring for the emergence of acquired resistance will be essential

A VELOUR post hoc subset analysis: prognostic groups and treatment outcomes in patients with metastatic colorectal cancer treated with aflibercept and FOLFIRI

The VELOUR study demonstrated a survival benefit for FOLFIRI + aflibercept versus FOLFIRI + placebo in metastatic colorectal cancer (mCRC) patients who progressed on oxaliplatin-based chemotherapy. Continued divergence of overall survival (OS) curves in the intension to treat (ITT) population, with the survival advantage persisting beyond median survival time, suggested subpopulations might have different magnitudes of survival gain. Additionally, 10% of patients within VELOUR had recurrence during or within 6 months of completing oxaliplatin-based adjuvant therapy (adjuvant fast relapsers) - previously identified as having poorer survival outcomes

Universal and wide shear zones in granular bulk flow

We present experiments on slow granular flows in a modified (split-bottomed) Couette geometry in which wide and tunable shear zones are created away from the sidewalls. For increasing layer heights, the zones grow wider (apparently without bound) and evolve towards the inner cylinder according to a simple, particle-independent scaling law. After rescaling, the velocity profiles across the zones fall onto a universal master curve given by an error function. We study the shear zones also inside the material as function of both their local height and the total layer height.Comment: Minor corrections, accepted for PRL (4 pages, 6 figures