Defining Prostatic Vascular Pedicle Recurrence and the Anatomy of Local Recurrence of Prostate Cancer on Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography.

Background The term local recurrence in prostate cancer is considered to mean persistent local disease in the prostatic bed, most commonly at the site of the vesicourethral anastomosis (VUA). Since the introduction of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging for assessment of early biochemical recurrence (BCR), we have found histologically confirmed prostate cancer in the prostatic vascular pedicle (PVP). If a significant proportion of local recurrences are distant to the VUA, it may be possible to alter adjuvant and salvage radiation fields in order to reduce the potential morbidity of radiation in selected patients. Objective To describe PVP local recurrence and to map the anatomic pattern of prostate bed recurrence on PSMA PET/CT. Design setting and participants This was a retrospective multicentre study of 185 patients imaged with PSMA PET/CT following radical prostatectomy (RP) between January 2016 and November 2018. All patient data and clinical outcomes were prospectively collected. Recurrences were documented according to anatomic location. For patients presenting with local recurrence, the precise location of the recurrence within the prostate bed was documented. Intervention PSMA PET/CT for BCR following RP. Results and limitations A total of 43 local recurrences in 41/185 patients (22%) were identified. Tumour recurrence at the PVP was found in 26 (63%), VUA in 15 (37%), and within a retained seminal vesicle and along the anterior rectal wall in the region of the neurovascular bundle in one (2.4%) each. Histological and surgical evidence of PVP recurrence was acquired in two patients. The study is limited by its retrospective nature with inherent selection bias. This is an observational study reporting on the anatomy of local recurrence and does not include follow-up for patient outcomes. Conclusions Our study showed that prostate cancer can recur in the PVP and is distant to the VUA more commonly than previously thought. This may have implications for RP technique and for the treatment of selected patients in the local recurrence setting. Patient summary We investigated more precise identification of the location of tumour recurrence after removal of the prostate for prostate cancer. We describe a new definition of local recurrence in an area called the prostatic vascular pedicle. This new concept may alter the treatment recommended for recurrent disease

Inborn Errors of Immunity on the Island of Ireland - a Cross-Jurisdictional UKPID/ESID Registry Report

Correction; Early Access:The epidemiology of inborn errors of immunity (IEI) in the Republic of Ireland was first published in 2005 but has not been updated since. IEI prevalence data from Northern Ireland was last published in 2018. Using data from the United Kingdom Primary Immune Deficiency (UKPID) and European Society for Immunodeficiencies (ESID) registries, we reviewed all registered cases of IEI affecting adult patients >= 18 years of age from the two largest immunology specialist centres in Northern Ireland and the Republic of Ireland, respectively and calculated the combined minimum adult prevalence of IEI on the island of Ireland for the first time. We also recorded data pertaining to presenting symptoms of IEI, diagnostic delay, immunoglobulin data, and genetic testing, as well as briefly reporting data pertaining to secondary immunodeficiency in both countries. As of 1 May 2020, we identified a minimum adult IEI prevalence in Ireland of 8.85/100,000 population.Peer reviewe

Inborn Errors of Immunity on the Island of Ireland - a Cross-Jurisdictional UKPID/ESID Registry Report

The epidemiology of inborn errors of immunity (IEI) in the Republic of Ireland was first published in 2005 but has not been updated since. IEI prevalence data from Northern Ireland was last published in 2018. Using data from the United Kingdom Primary Immune Deficiency (UKPID) and European Society for Immunodeficiencies (ESID) registries, we reviewed all registered cases of IEI affecting adult patients ≥ 18 years of age from the two largest immunology specialist centres in Northern Ireland and the Republic of Ireland, respectively and calculated the combined minimum adult prevalence of IEI on the island of Ireland for the first time. We also recorded data pertaining to presenting symptoms of IEI, diagnostic delay, immunoglobulin data, and genetic testing, as well as briefly reporting data pertaining to secondary immunodeficiency in both countries. As of 1 May 2020, we identified a minimum adult IEI prevalence in Ireland of 8.85/100,000 population

Wearable neuroimaging: Combining and contrasting magnetoencephalography and electroencephalography

One of the most severe limitations of functional neuroimaging techniques, such as magnetoencephalography (MEG), is that participants must maintain a fixed head position during data acquisition. This imposes restrictions on the characteristics of the experimental cohorts that can be scanned and the experimental questions that can be addressed. For these reasons, the use of ‘wearable’ neuroimaging, in which participants can move freely during scanning, is attractive. The most successful example of wearable neuroimaging is electroencephalography (EEG), which employs lightweight and flexible instrumentation that makes it useable in almost any experimental setting. However, EEG has major technical limitations compared to MEG, and therefore the development of wearable MEG, or hybrid MEG/EEG systems, is a compelling prospect. In this paper, we combine and compare EEG and MEG measurements, the latter made using a new generation of optically-pumped magnetometers (OPMs). We show that these new second generation commercial OPMs, can be mounted on the scalp in an ‘EEG-like’ cap, enabling the acquisition of high fidelity electrophysiological measurements. We show that these sensors can be used in conjunction with conventional EEG electrodes, offering the potential for the development of hybrid MEG/EEG systems. We compare concurrently measured signals, showing that, whilst both modalities offer high quality data in stationary subjects, OPM-MEG measurements are less sensitive to artefacts produced when subjects move. Finally, we show using simulations that OPM-MEG offers a fundamentally better spatial specificity than EEG. The demonstrated technology holds the potential to revolutionise the utility of functional brain imaging, exploiting the flexibility of wearable systems to facilitate hitherto impractical experimental paradigms

Optically pumped magnetometers: From quantum origins to multi-channel magnetoencephalography

Optically Pumped Magnetometers (OPMs) have emerged as a viable and wearable alternative to cryogenic, superconducting MEG systems. This new generation of sensors has the advantage of not requiring cryogenic cooling and as a result can be flexibly placed on any part of the body. The purpose of this review is to provide a neuroscience audience with the theoretical background needed to understand the physical basis for the signal observed by OPMs. Those already familiar with the physics of MRI and NMR should note that OPMs share much of the same theory as the operation of OPMs rely on magnetic resonance. This review establishes the physical basis for the signal equation for OPMs. We re-derive the equations defining the bounds on OPM performance and highlight the important trade-offs between quantities such as bandwidth, sensor size and sensitivity. These equations lead to a direct upper bound on the gain change due to cross-talk for a multi-channel OPM system

Multi-channel whole-head OPM-MEG: Helmet design and a comparison with a conventional system

© 2020 The Authors Magnetoencephalography (MEG) is a powerful technique for functional neuroimaging, offering a non-invasive window on brain electrophysiology. MEG systems have traditionally been based on cryogenic sensors which detect the small extracranial magnetic fields generated by synchronised current in neuronal assemblies, however, such systems have fundamental limitations. In recent years, non-cryogenic quantum-enabled sensors, called optically-pumped magnetometers (OPMs), in combination with novel techniques for accurate background magnetic field control, have promised to lift those restrictions offering an adaptable, motion-robust MEG system, with improved data quality, at reduced cost. However, OPM-MEG remains a nascent technology, and whilst viable systems exist, most employ small numbers of sensors sited above targeted brain regions. Here, building on previous work, we construct a wearable OPM-MEG system with ‘whole-head’ coverage based upon commercially available OPMs, and test its capabilities to measure alpha, beta and gamma oscillations. We design two methods for OPM mounting; a flexible (EEG-like) cap and rigid (additively-manufactured) helmet. Whilst both designs allow for high quality data to be collected, we argue that the rigid helmet offers a more robust option with significant advantages for reconstruction of field data into 3D images of changes in neuronal current. Using repeat measurements in two participants, we show signal detection for our device to be highly robust. Moreover, via application of source-space modelling, we show that, despite having 5 times fewer sensors, our system exhibits comparable performance to an established cryogenic MEG device. While significant challenges still remain, these developments provide further evidence that OPM-MEG is likely to facilitate a step change for functional neuroimaging

A Micro-Costing Study of Screening for Lynch Syndrome-Associated Pathogenic Variants in an Unselected Endometrial Cancer Population: Cheap as NGS Chips?

Background: Lynch syndrome is the most common inherited cause of endometrial cancer. Identifying individuals affected by Lynch syndrome enables risk-reducing interventions including colorectal surveillance, and cascade testing of relatives.Methods: We conducted a micro-costing study of screening all women with endometrial cancer for Lynch syndrome using one of four diagnostic strategies combining tumor microsatellite instability testing (MSI), immunohistochemistry (IHC), and/or MLH1 methylation testing, and germline next generation sequencing (NGS). Resource use (consumables, capital equipment, and staff) was identified through direct observation and laboratory protocols. Published sources were used to identify unit costs to calculate a per-patient cost (£; 2017) of each testing strategy, assuming a National Health Service (NHS) perspective.Results: Tumor triage with MSI and reflex MLH1 methylation testing followed by germline NGS of women with likely Lynch syndrome was the cheapest strategy at £42.01 per case. Tumor triage with IHC and reflex MLH1 methylation testing of MLH1 protein-deficient cancers followed by NGS of women with likely Lynch syndrome cost £45.68. Tumor triage with MSI followed by NGS of all women found to have tumor microsatellite instability cost £78.95. Immediate germline NGS of all women with endometrial cancer cost £176.24. The cost of NGS was affected by the skills and time needed to interpret results (£44.55/patient).Conclusion: This study identified the cost of reflex screening all women with endometrial cancer for Lynch syndrome, which can be used in a model-based cost-effectiveness analysis to understand the added value of introducing reflex screening into clinical practice

A Response to the Draft National Mitigation Plan. Teagasc submission to the Department of Communications, Climate Action & theEnvironment

Teagasc SubmissionThis submission details the mitigation potential of agriculture to shortly be published as an update to the Marginal Abatement Cost Curve (MACC) for Agriculture and and describes how the MACC mitigation strategies relate to the measures in the National Mitigation Plan

An Analysis of Abatement Potential of Greenhouse Gas Emissions in Irish Agriculture 2021-2030

Teagasc SubmissionThis report has been prepared by the Teagasc Working Group on GHG Emissions, which brings together and integrates the extensive and diverse range of organisational expertise on agricultural greenhouse gases. The previous Teagasc GHG MACC was published in 2012 in response to both the EU Climate and Energy Package and related Effort Sharing Decision and in the context of the establishment of the Food Harvest 2020 production targets

Strategies to address the shortcomings of commonly used advanced chronic heart failure descriptors to improve recruitment in palliative care research: A parallel mixed-methods feasibility study

Background:Recruitment challenges contribute to the paucity of palliative care research with advanced chronic heart failure patients.Aim:To describe the challenges and outline strategies of recruiting advanced chronic heart failure patients.Design:A feasibility study using a pre–post uncontrolled design.Setting:Advanced chronic heart failure patients were recruited at two nurse-led chronic heart failure disease management clinics in IrelandResults:Of 372 patients screened, 81 were approached, 38 were recruited (46.9% conversion to consent) and 25 completed the intervention. To identify the desired population, a modified version of the European Society of Cardiology definition was used together with modified New York Heart Association inclusion criteria to address inter-study site New York Heart Association classification subjectivity. These modifications substantially increased median monthly numbers of eligible patients approached (from 8 to 20) and median monthly numbers recruited (from 4 to 9). Analysis using a mortality risk calculator demonstrated that recruited patients had a median 1-year mortality risk of 22.7 and confirmed that the modified eligibility criteria successfully identified the population of interest. A statistically significant difference in New York Heart Association classification was found in recruited patients between study sites, but no statistically significant difference was found in selected clinical parameters between these patients.Conclusion:Clinically relevant modifications to the European Society of Cardiology definition and strategies to address New York Heart Association subjectivity may help to improve advanced chronic heart failure patient recruitment in clinical settings, thereby helping to address the paucity of palliative care research this population