PD-L1 testing for lung cancer in the UK: recognizing the challenges for implementation.

A new approach to the management of non-small-cell lung cancer (NSCLC) has recently emerged that works by manipulating the immune checkpoint controlled by programmed death receptor 1 (PD-1) and its ligand programmed death ligand 1 (PD-L1). Several drugs targeting PD-1 (pembrolizumab and nivolumab) or PD-L1 (atezolizumab, durvalumab, and avelumab) have been approved or are in the late stages of development. Inevitably, the introduction of these drugs will put pressure on healthcare systems, and there is a need to stratify patients to identify those who are most likely to benefit from such treatment. There is evidence that responsiveness to PD-1 inhibitors may be predicted by expression of PD-L1 on neoplastic cells. Hence, there is considerable interest in using PD-L1 immunohistochemical staining to guide the use of PD-1-targeted treatments in patients with NSCLC. This article reviews the current knowledge about PD-L1 testing, and identifies current research requirements. Key factors to consider include the source and timing of sample collection, pre-analytical steps (sample tracking, fixation, tissue processing, sectioning, and tissue prioritization), analytical decisions (choice of biomarker assay/kit and automated staining platform, with verification of standardized assays or validation of laboratory-devised techniques, internal and external quality assurance, and audit), and reporting and interpretation of the results. This review addresses the need for integration of PD-L1 immunohistochemistry with other tests as part of locally agreed pathways and protocols. There remain areas of uncertainty, and guidance should be updated regularly as new information becomes available

Deep Residual-Dense Lattice Network for Speech Enhancement

Convolutional neural networks (CNNs) with residual links (ResNets) and causal dilated convolutional units have been the network of choice for deep learning approaches to speech enhancement. While residual links improve gradient flow during training, feature diminution of shallow layer outputs can occur due to repetitive summations with deeper layer outputs. One strategy to improve feature re-usage is to fuse both ResNets and densely connected CNNs (DenseNets). DenseNets, however, over-allocate parameters for feature re-usage. Motivated by this, we propose the residual-dense lattice network (RDL-Net), which is a new CNN for speech enhancement that employs both residual and dense aggregations without over-allocating parameters for feature re-usage. This is managed through the topology of the RDL blocks, which limit the number of outputs used for dense aggregations. Our extensive experimental investigation shows that RDL-Nets are able to achieve a higher speech enhancement performance than CNNs that employ residual and/or dense aggregations. RDL-Nets also use substantially fewer parameters and have a lower computational requirement. Furthermore, we demonstrate that RDL-Nets outperform many state-of-the-art deep learning approaches to speech enhancement.Comment: 8 pages, Accepted by AAAI-202

e-VLBI observations of Circinus X-1: monitoring of the quiescent and flaring radio emission on AU scales

A recent detection of the peculiar neutron star X-ray binary Circinus X-1 with electronic very long baseline interferometry (e-VLBI) prompted the suggestion that compact, non-variable radio emission persists through the entire 16.6-day orbit of the binary system. We present the results of a high angular resolution monitoring campaign conducted with the Australian Long Baseline Array in real-time e-VLBI mode. e-VLBI observations of Circinus X-1 were made on alternate days over a period of 20 days covering the full binary orbit. A compact radio source associated with Circinus X-1 was clearly detected at orbital phases following periastron passage but no compact radio emission was detected at any other orbital phase, ruling out the presence of a persistent, compact emitting region at our sensitivity levels. The jet was not resolved at any epoch of our 1.4-GHz monitoring campaign, suggesting that the ultrarelativistic flow previously inferred to exist in this source is likely to be dark. We discuss these findings within the context of previous radio monitoring of Circinus X-1.Comment: Accepted for publication in MNRAS. 7 pages, 5 figure

Adult beginner distance language learner perceptions and use of assignment feedback

This qualitative study examines perceptions and use of assignment feedback among adult beginner modern foreign language learners on higher education distance learning courses. A survey of responses to feedback on assignments by 43 Open University students on beginner language courses in Spanish, French, and German indicated that respondents can be classified into three groups: those who use feedback strategically by integrating it into the learning process and comparing it with, for example, informal feedback from interaction with native speakers, those who take note of feedback, but seem not to use it strategically, and those who appear to take little account of either marks or feedback. The first group proved to be the most confident and most likely to maintain their motivation in the longer term. The conclusion discusses some of the pedagogical and policy implications of the findings

Psychological factors not strength deficits are associated with severity of gluteal tendinopathy: a cross-sectional study

Gluteal tendinopathy is the most common lower limb tendinopathy presenting to general practice. It has a high prevalence amongst middle-aged women and impacts on daily activities, work participation and quality of life. The aim was to compare physical and psychological characteristics between subgroups of severity of pain and disability.A multicentre cross-sectional cohort of 204 participants (mean age 55\ua0years, 82% female) who had a clinical diagnosis of gluteal tendinopathy with magnetic resonance imaging confirmation were assessed. A range of physical and psychosocial characteristics were recorded. Pain and disability were measured with the VISA-G questionnaire. A cluster analysis was used to identify mild, moderate and severe subgroups based on total VISA-G scores. Between-group differences were then evaluated with a MANCOVA, including sex and study site as covariates, followed by a Bonferroni post hoc test. Significance was set at 0.05.There were significantly higher pain catastrophizing and depression scores in the more severe subgroups. Lower pain self-efficacy scores were found in the severe group compared to the moderate and mild groups. Greater waist girth and body mass index (BMI), lower activity levels and poorer quality of life were reported in the severe group compared to the mild group. Hip abductor muscle strength and hip circumference did not differ between subgroups of severity.Individuals with severe gluteal tendinopathy present with psychological distress, poorer quality of life, greater BMI and waist girth. Given these features, the consideration of psychological factors in more severe patients may be important to optimize patient outcomes and reduce healthcare utilization.Patients with severe gluteal tendinopathy exhibit greater psychological distress, poorer quality of life and greater waist girth and BMI when compared to less severe cases. This implies that clinicians ought to consider psychological factors in the management of more severe gluteal tendinopathy