Training in priority assistive products: report from the first pilot

The first pilot of the training in priority assistive products package (TAP) was carried out in Bangalore, India in partnership with Mobility India and the Bangalore Baptist Hospital’s Community Health Division in collaboration with Motivation Australia, LV Prasad Eye Institute, and the University College London between the 27th February and the 2nd March 2018. The scope of the pilot was to identify potential barriers and facilitators to the future implementation of TAP; gather feedback from representative TAP users to inform ongoing development of TAP; as well as to pilot the evaluation methodology for future TAP pilots. This report aims to presents an overview of TAP and of the pilot, illustrate the key pilot findings, and highlights key recommendations going forward

The Gaussian Process Autoregressive Regression Model (GPAR)

Multi-output regression models must exploit dependencies between outputs to maximise predictive performance. The application of Gaussian processes (GPs) to this setting typically yields models that are computationally demanding and have limited representational power. We present the Gaussian Process Autoregressive Regression (GPAR) model, a scalable multi-output GP model that is able to capture nonlinear, possibly input-varying, dependencies between outputs in a simple and tractable way: the product rule is used to decompose the joint distribution over the outputs into a set of conditionals, each of which is modelled by a standard GP. GPAR's efficacy is demonstrated on a variety of synthetic and real-world problems, outperforming existing GP models and achieving state-of-the-art performance on established benchmarks

The NDE of Complex Liquids Containing Suspended Particles

Many products of commercial significance exist as suspensions of particles in a liquid or will have consisted as such as suspension at a stage during manufacture; the particles may be solid or liquid. It is necessary to determine the physical state of such suspensions both in the development laboratory and for the purposes of quality and process control at plant level. Reliable estimates are required of the size distribution and concentration of the dispersed phase, as well as indications of flocculation, and network formation. Dynamic measures may be required in support of reaction processes such as crystallization. Techniques that can be used for the characterisation of suspensions are optical scattering or turbidity tests, sedimentation rate tests, ionizing radiation, electrical tests, electroacoustic measurements, and acoustic (ultrasonic) methods alone. Ultrasonic methods have the advantages that they can be used on mixtures that are too opaque for optical techniques, and that they can be incorporated into robust and low cost instrumentation. This paper gives a brief overview of the physics of the interactions of ultrasonic waves with particulate suspensions and a brief review of measurement methods and errors. Recent results that show agreement or otherwise between theory and experiment are given for silica sols. Examples are also given of the use of ultrasound to track flocculation in an aqueous emulsion, and to track a crystallization reaction

Convolutional conditional neural processes for local climate downscaling

A new model is presented for multisite statistical downscaling of temperature and precipitation using convolutional conditional neural processes (convCNPs). ConvCNPs are a recently developed class of models that allow deep-learning techniques to be applied to off-the-grid spatio-temporal data. In contrast to existing methods that map from low-resolution model output to high-resolution predictions at a discrete set of locations, this model outputs a stochastic process that can be queried at an arbitrary latitude–longitude coordinate. The convCNP model is shown to outperform an ensemble of existing downscaling techniques over Europe for both temperature and precipitation taken from the VALUE intercomparison project. The model also outperforms an approach that uses Gaussian processes to interpolate single-site downscaling models at unseen locations. Importantly, substantial improvement is seen in the representation of extreme precipitation events. These results indicate that the convCNP is a robust downscaling model suitable for generating localised projections for use in climate impact studies

Can we accurately report PTEN status in advanced colorectal cancer?

BACKGROUND: Loss of phosphatase and tensin homologue (PTEN) function evaluated by loss of PTEN protein expression on immunohistochemistry (IHC) has been reported as both prognostic in metastatic colorectal cancer and predictive of response to anti-EGFR monoclonal antibodies although results remain uncertain. Difficulties in the methodological assessment of PTEN are likely to be a major contributor to recent conflicting results. METHODS: We assessed loss of PTEN function in 51 colorectal cancer specimens using Taqman® copy number variation (CNV) and IHC. Two blinded pathologists performed independent IHC assessment on each specimen and inter-observer variability of IHC assessment and concordance of IHC versus Taqman® CNV was assessed. RESULTS: Concordance between pathologists (PTEN loss vs no loss) on IHC assessment was 37/51 (73%). In specimens with concordant IHC assessment, concordance between IHC and Taqman® copy number in PTEN loss assessment was 25/37 (68%). CONCLUSION: Assessment PTEN loss in colorectal cancer is limited by the inter-observer variability of IHC, and discordance of CNV with loss of protein expression. An understanding of the genetic mechanisms of PTEN loss and implementation of improved and standardized methodologies of PTEN assessment are required to clarify the role of PTEN as a biomarker in colorectal cancer

canstem303c trial a phase 3 study of napabucasin napa in combination with 5 fluorouracil 5 fu leucovorin and irinotecan folfiri in adult patients pts with previously treated metastatic colorectal cancer mcrc trial in progress

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Does the chemotherapy backbone impact on the efficacy of targeted agents in metastatic colorectal cancer? A systematic review and meta-analysis of the literature

IMPORTANCE The EGFR inhibitors (EGFR-I) cetuximab and panitumumab and the angiogenesis inhibitors (AIs) bevacizumab and aflibercept have demonstrated varying efficacy in mCRC. OBJECTIVE To document the overall impact of specific chemotherapy regimens on the efficacy of targeted agents in treating patients with mCRC. Data sources: MEDLINE, EMBASE and Cochrane databases were searched to 2014, supplemented by hand-searching ASCO/ESMO conference abstracts. STUDY SELECTION Published RCTs of patients with histologically confirmed mCRC were included if they investigated either 1) chemotherapy with or without a biological agent or 2) different chemotherapy regimens with the same biological agent. EGFR-I trials were restricted to KRAS exon 2 wild-type (WT) populations. DATA EXTRACTION AND SYNTHESIS Data were independently abstracted by two authors and trial quality assessed according to Cochrane criteria. The primary outcome was overall survival with secondary endpoints progression free survival (PFS), overall response rate (ORR) and toxicity. RESULTS EGFR-I added to irinotecan-based chemotherapy modestly improved OS with HR 0.90 (95% CI 0.81–1.00, p = 0.04), but more so PFS with HR 0.77 (95% CI 0.69–0.86, p<0.00001). No benefit was evident for EGFR-I added to oxaliplatin-based chemotherapy (OS HR 0.97 (95% CI 0.87–1.09) and PFS HR 0.92 (95% CI 0.83–1.02)). Significant oxaliplatin-irinotecan subgroup interactions were present for PFS with I2 = 82%, p = 0.02. Further analyses of oxaliplatin+EGFR-I trials showed greater efficacy with infusional 5FU regimens (PFS HR 0.82, 95% CI 0.72–0.94) compared to capecitabine (HR 1.09; 95% CI 0.91–1.30) and bolus 5FU (HR 1.07; 95% CI 0.79–1.45); subgroup interaction was present with I2 = 72%, p = 0.03. The oxaliplatin-irinotecan interaction was not evident for infusional 5FU regimens. For AIs, OS benefit was observed with both oxaliplatin-based (HR 0.83) and irinotecan-based (HR 0.77) regimens without significant subgroup interactions. Oxaliplatin+AI trials showed no subgroup interactions by type of FP, whilst an interaction was present for irinotecan+AI trials although aflibercept was only used with infusional FP (I2 = 89.7%, p = 0.002). CONCLUSION AND RELEVANCE The addition of EGFR-I to irinotecan-based chemotherapy has consistent efficacy, regardless of FP regimen, whereas EGFR-I and oxaliplatin-based regimens were most active with infusional 5FU. No such differential activity was observed with the varying chemotherapy schedules when combined with AIs.David L. Chan, Nick Pavlakis, Jeremy Shapiro, Timothy J. Price, Christos S. Karapetis, Niall C. Tebbutt, Eva Segelo

Life after eruption - I. Spectroscopic observations of ten nova candidates

We have started a project to investigate the connection of post-novae with the population of cataclysmic variables. Our first steps in this concern improving the sample of known post-novae and their properties. Here we present the recovery and/or confirmation of the old novae MT Cen, V812 Cen, V655 CrA, IL Nor, V2109 Oph, V909 Sgr, V2572 Sgr, and V728 Sco. Principal photometric and spectroscopic properties of these systems are discussed. We find that V909 Sgr is a probable magnetic CV, and that V728 Sco is a high-inclination system. We furthermore suggest that the two candidate novae V734 Sco and V1310 Sgr have been misclassified and instead are Mira variables.Comment: 11 pages, 7 figures (some of them in lower resolution), to be published in MNRA

Feasibility and design of a trial regarding the optimal mode of delivery for preterm birth:the CASSAVA multiple methods study

Background: Around 60,000 babies are born preterm (prior to 37 weeks’ gestation) each year in the UK. There is little evidence on the optimal birth mode (vaginal or caesarean section). Objective: The overall aim of the CASSAVA project was to determine if a trial to define the optimal mode of preterm birth could be carried out and, if so, determine what sort of trial could be conducted and how it could best be performed. We aimed to determine the specific groups of preterm women and babies for whom there are uncertainties about the best planned mode of birth, and if there would be willingness to recruit to, and participate in, a randomised trial to address some, but not all, of these uncertainties. This project was conducted in response to a Heath Technology Assessment programme commissioning call (17/22 ‘Mode of delivery for preterm infants’). Methods: We conducted clinician and patient surveys (n = 224 and n = 379, respectively) to identify current practice and opinion, and a consensus survey and Delphi workshop (n = 76 and n = 22 participants, respectively) to inform the design of a hypothetical clinical trial. The protocol for this clinical trial/vignette was used in telephone interviews with clinicians (n = 24) and in focus groups with potential participants (n = 13). Results: Planned sample size and data saturation was achieved for all groups except for focus groups with participants, as this had to be curtailed because of the COVID-19 pandemic and data saturation was not achieved. There was broad agreement from parents and health-care professionals that a trial is needed. The clinician survey demonstrated a variety of practice and opinion. The parent survey suggested that women and their families generally preferred vaginal birth at later gestations and caesarean section for preterm infants. The interactive workshop and Delphi consensus process confirmed the need for more evidence (hence the case for a trial) and provided rich information on what a future trial should entail. It was agreed that any trial should address the areas with most uncertainty, including the management of women at 26–32 weeks’ gestation, with either spontaneous preterm labour (cephalic presentation) or where preterm birth was medically indicated. Clear themes around the challenges inherent in conducting any trial emerged, including the concept of equipoise itself. Specific issues were as follows: different clinicians and participants would be in equipoise for each clinical scenario, effective conduct of the trial would require appropriate resources and expertise within the hospital conducting the trial, potential participants would welcome information on the trial well before the onset of labour and minority ethnic groups would require tailored approaches. Conclusion: Given the lack of evidence and the variation of practice and opinion in this area, and having listened to clinicians and potential participants, we conclude that a trial should be conducted and the outlined challenges resolved. Future work: The CASSAVA project could be used to inform the design of a randomised trial and indicates how such a trial could be carried out. Any future trial would benefit from a pilot with qualitative input and a study within a trial to inform optimal recruitment. Limitations: Certainty that a trial could be conducted can be determined only when it is attempted. Trial registration: Current Controlled Trials ISRCTN12295730. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 61. See the NIHR Journals Library website for further project information