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We apply two methods to estimate the 21-cm bispectrum from data taken within the Epoch of Reionisation (EoR) project of the Murchison Widefield Array (MWA). Using data acquired with the Phase II compact array allows a direct bispectrum estimate to be undertaken on the multiple redundantly spaced triangles of antenna tiles, as well as an estimate based on data gridded to the uv-plane. The direct and gridded bispectrum estimators are applied to 21 h of high-band (167–197 MHz; z = 6.2–7.5) data from the 2016 and 2017 observing seasons. Analytic predictions for the bispectrum bias and variance for point-source foregrounds are derived. We compare the output of these approaches, the foreground contribution to the signal, and future prospects for measuring the bispectra with redundant and non-redundant arrays. We find that some triangle configurations yield bispectrum estimates that are consistent with the expected noise level after 10 h, while equilateral configurations are strongly foreground-dominated. Careful choice of triangle configurations may be made to reduce foreground bias that hinders power spectrum estimators, and the 21-cm bispectrum may be accessible in less time than the 21-cm power spectrum for some wave modes, with detections in hundreds of hours.
Background: Cannabis has been shown to be an effective therapy for epilepsy in children with Dravet and Lennox-Gastaut syndrome. Despite the fact that many pediatric epilepsy patients across Canada are currently being treated with cannabis, little is known about pediatric neurologists’ attitudes towards it. Methods: A 26-item online survey was distributed to 148 pediatric neurologists across Canada. Results: 56/148 neurologists responded and reported that over 600 children with epilepsy are currently taking cannabinoids. 34% of neurologists authorized cannabis to children, 38% referred children for authorization, and 29% did not authorize or refer their patients. Of those neurologists who referred, 76% referred to a community-based non-neurologist. The majority of physicians authorized cannabis to patients with Dravet syndrome (68%) and Lennox-Gastaut syndrome (64%). Cannabis was never authorized as a first-line treatment. 54% of neurologists stated that their patients were taking CBD alone, despite this option not being available in Canada. All physicians reported having at least one hesitation regarding cannabis, the most common ones being poor evidence (66%), poor quality control (52%), and cost (50%). Conclusions: The majority of Canadian pediatric neurologists use cannabis as a treatment for epilepsy in children. However, there appear to be knowledge gaps and hesitations.
Background: Biallelic variants in POLR1C are associated with POLR3-related leukodystrophy (POLR3-HLD), or 4H leukodystrophy (Hypomyelination, Hypodontia, Hypogonadotropic Hypogonadism), and Treacher Collins syndrome (TCS). The clinical spectrum of POLR3-HLD caused by variants in this gene has not been described. Methods: A cross-sectional observational study involving 25 centers worldwide was conducted between 2016 and 2018. The clinical, radiologic and molecular features of 23 unreported and previously reported cases of POLR3-HLD caused by POLR1C variants were reviewed. Results: Most participants presented between birth and age 6 years with motor difficulties. Neurological deterioration was seen during childhood, suggesting a more severe phenotype than previously described. The dental, ocular and endocrine features often seen in POLR3-HLD were not invariably present. Five patients (22%) had a combination of hypomyelinating leukodystrophy and abnormal craniofacial development, including one individual with clear TCS features. Several cases did not exhibit all the typical radiologic characteristics of POLR3-HLD. A total of 29 different pathogenic variants in POLR1C were identified, including 13 new disease-causing variants. Conclusions: Based on the largest cohort of patients to date, these results suggest novel characteristics of POLR1C-related disorder, with a spectrum of clinical involvement characterized by hypomyelinating leukodystrophy with or without abnormal craniofacial development reminiscent of TCS.
Background: The classic ketogenic diet is the main non-pharmacological treatment for refractory epilepsy; however, adherence is often challenging. The low glycemic index diet (LGID) is less strict, almost equally effective, and associated with improved adherence. Little is known about the quality of life of children treated with LGID. The objective of this study was to explore changes in the quality of life of children with epilepsy transitioning to the LGID. Methods: Patients on LGID and their parents filled out Pediatric Quality of Life Epilepsy Module questionnaires; one while being on the LGID, and one retrospectively for the time prior to starting the LGID. Results: Data was collected from five children ages 3-13 and their parents. Complete seizure control was seen in two children, >50% seizure reduction in one, and no change in two children. Parental reported quality of life while on the LGID increased with two participants but decreased in all child self reports. Conclusions: Although the LGID led to improved seizure control in three out of five patients, the child-reported quality of life decreased in all children. Larger prospective studies are warranted to reliably assess the impact of the LGID on the quality of life in children with epilepsy.
Background: Seizure monitoring via amplitude-integrated EEG (aEEG) is standard of care in many NICUs; however, conventional EEG (cEEG) is the gold standard for seizure detection. We compared the diagnostic yield of aEEG interpreted at the bedside, aEEG interpreted by an expert, and cEEG. Methods: Neonates received aEEG and cEEG in parallel. Clinical events and aEEG were interpreted at bedside and subsequently independently analyzed by experienced neonatology and neurology readers. Sensitivity and specificity of bedside aEEG as compared to expert aEEG interpretation and cEEG were evaluated. Results: Thirteen neonates were monitored for an average duration of 33 hours (range 15-94). Fourteen seizure-like events were detected by clinical observation, and 12 others by bedside aEEG analysis. None of the bedside aEEG events were confirmed as seizures on cEEG. Expert aEEG interpretation had a sensitivity of 13% with 46% specificity for individual seizure detection (not adjusting for patient differences), and a sensitivity of 50% with 46% specificity for detecting patients with seizures. Conclusions: Real-world bedside aEEG monitoring failed to detect seizures evidenced via cEEG, while misclassifying other events as seizures. Even post-hoc expert aEEG interpretation provided limited sensitivity and specificity. Considering the poor sensitivity and specificity of bedside aEEG interpretation, combined monitoring may provide limited clinical benefit.
We provide the first in situ measurements of antenna element beam shapes of the Murchison Widefield Array. Most current processing pipelines use an assumed beam shape, which can cause absolute and relative flux density errors and polarisation ‘leakage’. Understanding the primary beam is then of paramount importance, especially for sensitive experiments such as a measurement of the 21-cm line from the epoch of reionisation, where the calibration requirements are so extreme that tile to tile beam variations may affect our ability to make a detection. Measuring the primary beam shape from visibilities is challenging, as multiple instrumental, atmospheric, and astrophysical factors contribute to uncertainties in the data. Building on the methods of Neben et al. [Radio Sci., 50, 614], we tap directly into the receiving elements of the telescope before any digitisation or correlation of the signal. Using ORBCOMM satellite passes we are able to produce all-sky maps for four separate tiles in the XX polarisation. We find good agreement with the beam model of Sokolowski et al. [2017, PASA, 34, e062], and clearly observe the effects of a missing dipole from a tile in one of our beam maps. We end by motivating and outlining additional on-site experiments.
We describe the motivation and design details of the ‘Phase II’ upgrade of the Murchison Widefield Array radio telescope. The expansion doubles to 256 the number of antenna tiles deployed in the array. The new antenna tiles enhance the capabilities of the Murchison Widefield Array in several key science areas. Seventy-two of the new tiles are deployed in a regular configuration near the existing array core. These new tiles enhance the surface brightness sensitivity of the array and will improve the ability of the Murchison Widefield Array to estimate the slope of the Epoch of Reionisation power spectrum by a factor of ∼3.5. The remaining 56 tiles are deployed on long baselines, doubling the maximum baseline of the array and improving the array u, v coverage. The improved imaging capabilities will provide an order of magnitude improvement in the noise floor of Murchison Widefield Array continuum images. The upgrade retains all of the features that have underpinned the Murchison Widefield Array’s success (large field of view, snapshot image quality, and pointing agility) and boosts the scientific potential with enhanced imaging capabilities and by enabling new calibration strategies.
In Cameroon, there is a national programme engaged in the control of schistosomiasis and soil-transmitted helminthiasis. In certain locations, the programme is transitioning from morbidity control towards local interruption of parasite transmission. The volcanic crater lake villages of Barombi Mbo and Barombi Kotto are well-known transmission foci and are excellent context-specific locations to assess appropriate disease control interventions. Most recently they have served as exemplars of expanded access to deworming medications and increased environmental surveillance. In this paper, we review infection dynamics through time, beginning with data from 1953, and comment on the short- and long-term success of disease control. We show how intensification of local control is needed to push towards elimination and that further environmental surveillance, with targeted snail control, is needed to consolidate gains in preventive chemotherapy as well as empower local communities to take ownership of interventions.
The current emphasis of schistosomiasis control is placed on preventive chemotherapy using praziquantel. However, reinfection may occur rapidly in the absence of complementary interventions. Recent studies from Senegal suggest that predatory prawns might feed on intermediate host snails and thus impact on schistosomiasis transmission. We designed a study with four repeated cross-sectional surveys pertaining to prawns and snails, coupled with a single cross-sectional parasitological survey among humans. We assessed for potential associations between the presence/density of prawns and snails and correlation with Schistosoma infection in a composite sample of school-aged children and adults. The study was carried out between October 2015 and December 2016 in 24 villages located near the Agnéby and Mé coastal river systems in south-eastern Côte d'Ivoire. At each site, snails and prawns were collected, and in each village, 150 individuals were subjected to stool and urine examination for the diagnosis of Schistosoma mansoni and S. haematobium. We found peaks of relative abundance of intermediate host snails in the villages of the Agnéby River system, while predatory prawns were predominantly recorded in the Mé River system. A negative association was observed between intermediate host snail densities and riverine prawns; however, no pattern was found between this trend in the predator–prey relationship and the prevalence of human schistosomiasis.
The study of parasites typically crosses into other research disciplines and spans across diverse scales, from molecular- to populational-levels, notwithstanding promoting an understanding of parasites set within evolutionary time. Today, the 2030 Sustainable Development Goals (SDGs) help frame much of contemporary parasitological research, since parasites can be found in all ecosystems, blighting human, animal and plant health. In recognition of the multi-disciplinary nature of parasitological research, the 2017 Autumn Symposium of the British Society for Parasitology was held in London to provide a forum for novel exchange across medical, veterinary and wildlife fields of study. Whilst the meeting was devoted to the topic of parasitism, it sought to foster mutualism, the antithesis perhaps of parasitism, by forging new academic connections and social networks to exchange novel ideas. The meeting also celebrated the longstanding career of Professor David Rollinson, FLS in the award of the International Federation for Tropical Medicine Medal for his efforts spanning 40 years of parasitological research. Indeed, David has done so much to explore and promote the fascinating biology of parasitism, as exemplified by the 15 manuscripts contained within this Special Issue.
With the push towards control and elimination of soil-transmitted helminthiasis and schistosomiasis in low- and middle-income countries, there is a need to develop alternative diagnostic assays that complement the current in-country resources, preferably at a lower cost. Here, we describe a novel high-resolution melt (HRM) curve assay with six PCR primer pairs, designed to sub-regions of the nuclear ribosomal locus. Used within a single reaction and dye detection channel, they are able to discriminate Ancylostoma duodenale, Necator americanus, Strongyloides stercoralis, Ascaris lumbricoides, Trichuris trichiuria and Schistosoma spp. by HRM curve analysis. Here we describe the primers and the results of a pilot assessment whereby the HRM assay was tested against a selection of archived fecal samples from Ghanaian children as characterized by Kato–Katz and real-time PCR analysis with species-specific TaqMan hydrolysis probes. The resulting sensitivity and specificity of the HRM was 80 and 98.6% respectively. We judge the assay to be appropriate in modestly equipped and resourced laboratories. This method provides a potentially cheaper alternative to the TaqMan method for laboratories in lower resource settings. However, the assay requires a more extensive assessment as the samples used were not representative of all target organisms.
Forecasting the future is fun but futile since most forecasts are wrong. The only constructive strategy is to plan for the unknown. Therefore this talk will contain (almost) no predictions. It will simply consider how we may best cope with the shock of the new; the information explosion, the accelerating pace of change and its bewildering changes of direction. To do this we need to hold fast to a small number of big, lasting truths. I can survive on four, two of which are humanistic, two simply biological. These are:
Biological systems evolve through modification by natural selection. The word ‘modification’ does not imply new creation but redesign from a relatively small range of standard parts and processes to meet changing needs.
The application of reason is an effective and honest approach to the process of discovery and understanding. Almost all issues can benefit from application of the scientific method (reason challenged by experiment). However, almost all issues also contain elements that transcend science but these too are amenable to reason.
Humans are sentient animals. In common with other sentient animals, we are powerfully motivated by how we feel (as distinct from what we think) and most powerfully motivated by the need to feel good. This need may be physical or spiritual. The physical need to enjoy comfort, the satisfaction of a good meal, or sex, ensures our genetic survival. The emotional need for security, or spiritual satisfaction ensures the stability of our communities, since in a stable community, discretion and goodness have survival value.
All life forms have value. Moral philosophy argues that a life form such as a tree has an intrinsic value independent of its extrinsic value to us (e.g. for its beauty, utility or as a carbon sink). While I accept the concept of intrinsic value, I suggest that it is more useful to redefine the concept of extrinsic value in a less anthropocentric way (e.g. a tree has extrinsic value to a squirrel).
Helminth infections have large negative impacts on production efficiency in ruminant farming systems worldwide, and their effective management is essential if livestock production is to increase to meet future human needs for dietary protein. The control of helminths relies heavily on routine use of chemotherapeutics, but this approach is unsustainable as resistance to anthelmintic drugs is widespread and increasing. At the same time, infection patterns are being altered by changes in climate, land-use and farming practices. Future farms will need to adopt more efficient, robust and sustainable control methods, integrating ongoing scientific advances. Here, we present a vision of helminth control in farmed ruminants by 2030, bringing to bear progress in: (1) diagnostic tools, (2) innovative control approaches based on vaccines and selective breeding, (3) anthelmintics, by sustainable use of existing products and potentially new compounds, and (4) rational integration of future control practices. In this review, we identify the technical advances that we believe will place new tools in the hands of animal health decision makers in 2030, to enhance their options for control and allow them to achieve a more integrated and sustainable approach to helminth control in support of animal welfare and production.
The re-emergence of debates on the decolonisation of knowledge has revived interest in the National Question, which began over a century ago and remains unresolved. Tensions that were suppressed and hidden in the past are now being openly debated. Despite this, the goal of one united nation living prosperously under a constitutional democracy remains elusive. This edited volume examines the way in which various strands of left thought have addressed the National Question, especially during the apartheid years, and goes on to discuss its relevance for South Africa today and in the future. Instead of imposing a particular understanding of the National Question, the editors identified a number of political traditions and allowed contributors the freedom to define the question as they believed appropriate – in other words, to explain what they thought was the Unresolved National Question. This has resulted in a rich tapestry of interweaving perceptions. The volume is structured in two parts. The first examines four foundational traditions: Marxism-Leninism (the Colonialism of a Special Type thesis); the Congress tradition; the Trotskyist tradition; and Africanism. The second part explores the various shifts in the debate from the 1960s onwards, and includes chapters on Afrikaner nationalism, ethnic issues, black consciousness, feminism, workerism and constitutionalism. The editors hope that by revisiting the debates not popularly known among the scholarly mainstream, this volume will become a catalyst for an enriched debate on our identity and our future.