Neuroprotective benefits of proton beam therapy for paediatric central nervous system tumours: a review of evidence

Introduction Proton beam therapy (PBT) is often used for paediatric central nervous system (CNS) tumours for its potential to reduce neurocognitive effects. This is due to the dosimetric properties of PBT, providing a more conformal dose to the target volume and lower integral dose to healthy tissue compared with photon therapy. This helps lower dose to critical structures in the brain, reduce long-term neurocognitive deficits and potentially improve quality of life (QOL). This literature review aims to examine the neuroprotective benefits of PBT in paediatric patients diagnosed with CNS tumours at the longest possible follow-up to determine if these hypotheses continue to provide comparable QOL to the normative population. Method PubMed and Scopus were systematically searched to identify appropriate studies on neurocognitive late effects following PBT according to PRISMA protocols. Key words were chosen based on PICO criteria with main themes including PBT, paediatric CNS tumours and neurocognitive tests. Results Ten papers were selected and appraised (mean no. of patients(range): 63.1 (18 -114)). All reports included PBT only, with seven including Craniospinal Irradiation (CSI). One exception for photon contingency treatment was accepted. The most common tumour types identified were craniopharyngioma, ependymoma, intracranial germ cell tumour, low- and intermediate-grade gliomas and medulloblastoma. Over half of the studies included baseline assessments. In general, Full Scale Intelligence Quotient (FSIQ) was not observed to differ significantly from the normative population. Deficits at follow-up were often predicted at baseline showing the diagnosis alone could be indicative of poor neurocognitive function. Significantly poorer outcomes were observed following CSI treatment, compared with focal treatment where minor cognitive changes were identified in characteristics such as processing speed and working memory index. Tumour location was identified as a predictor for poor neurological status, with basal ganglia germ cell tumours demonstrating the most deficit compared to other locations. Conclusion Evidence continues to indicate cognitive sparing years after treatment, due to beneficial dosimetric properties of PBT. Patients receiving focal treatment demonstrated a consistently lower risk of cognitive deficits compared to CSI patients; indicating a requirement for separate research directives. Reduced dose to certain cranial structures may be a protector of long-term neurocognitive deficit. Longer-term follow up is required to determine if cognitive risk continues to stay within the limits of the normative population or decreases over time. Neuroprotective benefits of PBT were seen across much of the data, indicating PBT continues to spare cognitive function over time. Key words: Paediatric CNS tumour, Proton beam therapy, Neurocognitiv

Activation of the innate immune receptor Dectin-1 upon formation of a 'phagocytic synapse'.

Innate immune cells must be able to distinguish between direct binding to microbes and detection of components shed from the surface of microbes located at a distance. Dectin-1 (also known as CLEC7A) is a pattern-recognition receptor expressed by myeloid phagocytes (macrophages, dendritic cells and neutrophils) that detects β-glucans in fungal cell walls and triggers direct cellular antimicrobial activity, including phagocytosis and production of reactive oxygen species (ROS). In contrast to inflammatory responses stimulated upon detection of soluble ligands by other pattern-recognition receptors, such as Toll-like receptors (TLRs), these responses are only useful when a cell comes into direct contact with a microbe and must not be spuriously activated by soluble stimuli. In this study we show that, despite its ability to bind both soluble and particulate β-glucan polymers, Dectin-1 signalling is only activated by particulate β-glucans, which cluster the receptor in synapse-like structures from which regulatory tyrosine phosphatases CD45 and CD148 (also known as PTPRC and PTPRJ, respectively) are excluded (Supplementary Fig. 1). The 'phagocytic synapse' now provides a model mechanism by which innate immune receptors can distinguish direct microbial contact from detection of microbes at a distance, thereby initiating direct cellular antimicrobial responses only when they are required

Development of a patient-centred, evidence-based and consensus-based discharge care bundle for patients with acute exacerbation of chronic obstructive pulmonary disease

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted. https://bmjopenrespres.bmj.com/content/bmjresp/5/1/e000265.full.pdfAlberta Innovates Health Solutions Partnership for Research and Innovation in the Health System Program (AIHS PRIHS 201400390), Alberta Health ServicesPeer ReviewedIntroduction: Hospital and emergency department discharge for patients with chronic obstructive pulmonary disease (COPD) is often poorly organised. We developed a patient-centred, evidence-based and consensus-based discharge care bundle for patients with acute exacerbations of COPD. Methods: A purposeful sample of clinicians and patients were invited to participate in a two-round Delphi study (July–November 2015). In round 1, participants rated on a seven-point Likert scale (1=not at all important; 7=extremely important) the importance of 29 unique COPD care actions. Round 2 comprised items selected from round 1 based on consensus (>80%endorsement for Likert values 5–7). A list of 18 care items from round 2 was discussed in a face-to-face nominal group meeting. Results: Seven care items were included in the COPD discharge bundle based on clinician and patient input: (1) ensure adequate inhaler technique is demonstrated; (2) send discharge summary to family physician and arrange follow-up; (3) optimise and reconcile prescription of respiratory medications; (4) provide a written discharge management plan and assess patient’s and caregiver’s comprehension of discharge instructions; (5) refer to pulmonary rehabilitation; (6) screen for frailty and comorbidities; and (7) assess smoking status, provide counselling and refer to smoking cessation programme. Conclusion: We present a seven-item, patient-centred, evidence-based and consensus-based discharge bundle for patients with acute exacerbations of COPD. Alignment with clinical practice guidelines and feasibility of local adaptations of the bundle should be explored to facilitate wide applicability and evaluation of the effectiveness of the COPD discharge bundle

Metagenomics of Wastewater Influent from Wastewater Treatment Facilities across Ontario in the Era of Emerging SARS-CoV-2 Variants of Concern

We report metagenomic sequencing analyses of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in composite wastewater influent from 10 regions in Ontario, Canada, during the transition between Delta and Omicron variants of concern. The Delta and Omicron BA.1/BA.1.1 and BA.2-defining mutations occurring in various frequencies were reported in the consensus and subconsensus sequences of the composite samples

Using Strategic Movement to Calibrate a Neural Compass: A Spiking Network for Tracking Head Direction in Rats and Robots

The head direction (HD) system in mammals contains neurons that fire to represent the direction the animal is facing in its environment. The ability of these cells to reliably track head direction even after the removal of external sensory cues implies that the HD system is calibrated to function effectively using just internal (proprioceptive and vestibular) inputs. Rat pups and other infant mammals display stereotypical warm-up movements prior to locomotion in novel environments, and similar warm-up movements are seen in adult mammals with certain brain lesion-induced motor impairments. In this study we propose that synaptic learning mechanisms, in conjunction with appropriate movement strategies based on warm-up movements, can calibrate the HD system so that it functions effectively even in darkness. To examine the link between physical embodiment and neural control, and to determine that the system is robust to real-world phenomena, we implemented the synaptic mechanisms in a spiking neural network and tested it on a mobile robot platform. Results show that the combination of the synaptic learning mechanisms and warm-up movements are able to reliably calibrate the HD system so that it accurately tracks real-world head direction, and that calibration breaks down in systematic ways if certain movements are omitted. This work confirms that targeted, embodied behaviour can be used to calibrate neural systems, demonstrates that ‘grounding’ of modelled biological processes in the real world can reveal underlying functional principles (supporting the importance of robotics to biology), and proposes a functional role for stereotypical behaviours seen in infant mammals and those animals with certain motor deficits. We conjecture that these calibration principles may extend to the calibration of other neural systems involved in motion tracking and the representation of space, such as grid cells in entorhinal cortex

Evaluation of the Oscillatory Interference Model of Grid Cell Firing through Analysis and Measured Period Variance of Some Biological Oscillators

Models of the hexagonally arrayed spatial activity pattern of grid cell firing in the literature generally fall into two main categories: continuous attractor models or oscillatory interference models. Burak and Fiete (2009, PLoS Comput Biol) recently examined noise in two continuous attractor models, but did not consider oscillatory interference models in detail. Here we analyze an oscillatory interference model to examine the effects of noise on its stability and spatial firing properties. We show analytically that the square of the drift in encoded position due to noise is proportional to time and inversely proportional to the number of oscillators. We also show there is a relatively fixed breakdown point, independent of many parameters of the model, past which noise overwhelms the spatial signal. Based on this result, we show that a pair of oscillators are expected to maintain a stable grid for approximately t = 5µ3/(4πσ)2 seconds where µ is the mean period of an oscillator in seconds and σ2 its variance in seconds2. We apply this criterion to recordings of individual persistent spiking neurons in postsubiculum (dorsal presubiculum) and layers III and V of entorhinal cortex, to subthreshold membrane potential oscillation recordings in layer II stellate cells of medial entorhinal cortex and to values from the literature regarding medial septum theta bursting cells. All oscillators examined have expected stability times far below those seen in experimental recordings of grid cells, suggesting the examined biological oscillators are unfit as a substrate for current implementations of oscillatory interference models. However, oscillatory interference models can tolerate small amounts of noise, suggesting the utility of circuit level effects which might reduce oscillator variability. Further implications for grid cell models are discussed

Major histocompatibility complex class I molecules protect motor neurons from astrocyte-induced toxicity in amyotrophic lateral sclerosis

Astrocytes isolated from individuals with amyotrophic lateral sclerosis (ALS) are toxic to motor neurons (MNs) and play a non–cell autonomous role in disease pathogenesis. The mechanisms underlying the susceptibility of MNs to cell death remain unclear. Here we report that astrocytes derived from either mice bearing mutations in genes associated with ALS or human subjects with ALS reduce the expression of major histocompatibility complex class I (MHCI) molecules on MNs; reduced MHCI expression makes these MNs susceptible to astrocyte-induced cell death. Increasing MHCI expression on MNs increases survival and motor performance in a mouse model of ALS and protects MNs against astrocyte toxicity. Overexpression of a single MHCI molecule, HLA-F, protects human MNs from ALS astrocyte–mediated toxicity, whereas knockdown of its receptor, the killer cell immunoglobulin-like receptor KIR3DL2, on human astrocytes results in enhanced MN death. Thus, our data indicate that, in ALS, loss of MHCI expression on MNs renders them more vulnerable to astrocyte-mediated toxicity

Sources of Variability of Evapotranspiration in California

The variability (1990–2002) of potential evapotranspiration estimates (ETo) and related meteorological variables from a set of stations from the California Irrigation Management System (CIMIS) is studied. Data from the National Climatic Data Center (NCDC) and from the Department of Energy from 1950 to 2001 were used to validate the results. The objective is to determine the characteristics of climatological ETo and to identify factors controlling its variability (including associated atmospheric circulations). Daily ETo anomalies are strongly correlated with net radiation (Rn) anomalies, relative humidity (RH), and cloud cover, and less with average daily temperature (Tavg). The highest intraseasonal variability of ETo daily anomalies occurs during the spring, mainly caused by anomalies below the high ETo seasonal values during cloudy days. A characteristic circulation pattern is associated with anomalies of ETo and its driving meteorological inputs, Rn, RH, and Tavg, at daily to seasonal time scales. This circulation pattern is dominated by 700-hPa geopotential height (Z700) anomalies over a region off the west coast of North America, approximately between 32° and 44° latitude, referred to as the California Pressure Anomaly (CPA). High cloudiness and lower than normal ETo are associated with the low-height (pressure) phase of the CPA pattern. Higher than normal ETo anomalies are associated with clear skies maintained through anomalously high Z700 anomalies offshore of the North American coast. Spring CPA, cloudiness, maximum temperature (Tmax), pan evaporation (Epan), and ETo conditions have not trended significantly or consistently during the second half of the twentieth century in California. Because it is not known how cloud cover and humidity will respond to climate change, the response of ETo in California to increased greenhouse-gas concentrations is essentially unknown; however, to retain the levels of ETo in the current climate, a decline of Rn by about 6% would be required to compensate for a warming of +3°C.California Department of Water Resources/[4600002292]//Estados UnidosCalifornia Energy Commission///Estados UnidosU.S. Department of Energy///Estados UnidosUniversidad de Costa Rica//UCR/Costa RicaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigaciones Geofísicas (CIGEFI

Measuring progress and projecting attainment on the basis of past trends of the health-related Sustainable Development Goals in 188 countries: an analysis from the Global Burden of Disease Study 2016

The UN’s Sustainable Development Goals (SDGs) are grounded in the global ambition of “leaving no one behind”. Understanding today’s gains and gaps for the health-related SDGs is essential for decision makers as they aim to improve the health of populations. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016), we measured 37 of the 50 health-related SDG indicators over the period 1990–2016 for 188 countries, and then on the basis of these past trends, we projected indicators to 2030