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The Murchison Widefield Array (MWA) is an open access telescope dedicated to studying the low-frequency (80–300 MHz) southern sky. Since beginning operations in mid-2013, the MWA has opened a new observational window in the southern hemisphere enabling many science areas. The driving science objectives of the original design were to observe 21 cm radiation from the Epoch of Reionisation (EoR), explore the radio time domain, perform Galactic and extragalactic surveys, and monitor solar, heliospheric, and ionospheric phenomena. All together
programs recorded 20 000 h producing 146 papers to date. In 2016, the telescope underwent a major upgrade resulting in alternating compact and extended configurations. Other upgrades, including digital back-ends and a rapid-response triggering system, have been developed since the original array was commissioned. In this paper, we review the major results from the prior operation of the MWA and then discuss the new science paths enabled by the improved capabilities. We group these science opportunities by the four original science themes but also include ideas for directions outside these categories.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
The search for life in the Universe is a fundamental problem of astrobiology and modern science. The current progress in the detection of terrestrial-type exoplanets has opened a new avenue in the characterization of exoplanetary atmospheres and in the search for biosignatures of life with the upcoming ground-based and space missions. To specify the conditions favourable for the origin, development and sustainment of life as we know it in other worlds, we need to understand the nature of global (astrospheric), and local (atmospheric and surface) environments of exoplanets in the habitable zones (HZs) around G-K-M dwarf stars including our young Sun. Global environment is formed by propagated disturbances from the planet-hosting stars in the form of stellar flares, coronal mass ejections, energetic particles and winds collectively known as astrospheric space weather. Its characterization will help in understanding how an exoplanetary ecosystem interacts with its host star, as well as in the specification of the physical, chemical and biochemical conditions that can create favourable and/or detrimental conditions for planetary climate and habitability along with evolution of planetary internal dynamics over geological timescales. A key linkage of (astro)physical, chemical and geological processes can only be understood in the framework of interdisciplinary studies with the incorporation of progress in heliophysics, astrophysics, planetary and Earth sciences. The assessment of the impacts of host stars on the climate and habitability of terrestrial (exo)planets will significantly expand the current definition of the HZ to the biogenic zone and provide new observational strategies for searching for signatures of life. The major goal of this paper is to describe and discuss the current status and recent progress in this interdisciplinary field in light of presentations and discussions during the NASA Nexus for Exoplanetary System Science funded workshop ‘Exoplanetary Space Weather, Climate and Habitability’ and to provide a new roadmap for the future development of the emerging field of exoplanetary science and astrobiology.
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.
To compare the epidemiologic features (e.g. settings and transmission mode) and patient clinical characteristics associated with outbreaks of different norovirus (Nov) strains, we retrospectively analysed data of Nov outbreaks occurring in Guangzhou, China from 2012 to 2018. The results suggested that outbreaks of Nov GII.2, GII.17 and GII.4 Sydney exhibited different outbreak settings, transmission modes and symptoms. GII.2 outbreaks mainly occurred in kindergartens, elementary and high schools and were transmitted mainly through person-to-person contact. By contrast, GII.4 Sydney outbreaks frequently occurred in colleges and were primarily associated with foodborne transmission. Cases from GII.2 and GII.17 outbreaks reported vomiting more frequently than those from outbreaks associated with GII.4 Sydney.
Childhood maltreatment (CM) plays an important role in the development of major depressive disorder (MDD). The aim of this study was to examine whether CM severity and type are associated with MDD-related brain alterations, and how they interact with sex and age.
Within the ENIGMA-MDD network, severity and subtypes of CM using the Childhood Trauma Questionnaire were assessed and structural magnetic resonance imaging data from patients with MDD and healthy controls were analyzed in a mega-analysis comprising a total of 3872 participants aged between 13 and 89 years. Cortical thickness and surface area were extracted at each site using FreeSurfer.
CM severity was associated with reduced cortical thickness in the banks of the superior temporal sulcus and supramarginal gyrus as well as with reduced surface area of the middle temporal lobe. Participants reporting both childhood neglect and abuse had a lower cortical thickness in the inferior parietal lobe, middle temporal lobe, and precuneus compared to participants not exposed to CM. In males only, regardless of diagnosis, CM severity was associated with higher cortical thickness of the rostral anterior cingulate cortex. Finally, a significant interaction between CM and age in predicting thickness was seen across several prefrontal, temporal, and temporo-parietal regions.
Severity and type of CM may impact cortical thickness and surface area. Importantly, CM may influence age-dependent brain maturation, particularly in regions related to the default mode network, perception, and theory of mind.
The seasonality of individual influenza subtypes/lineages and the association of influenza epidemics with meteorological factors in the tropics/subtropics have not been well understood. The impact of the 2009 H1N1 pandemic on the prevalence of seasonal influenza virus remains to be explored. Using wavelet analysis, the periodicities of A/H3N2, seasonal A/H1N1, A/H1N1pdm09, Victoria and Yamagata were identified, respectively, in Panzhihua during 2006–2015. As a subtropical city in southwestern China, Panzhihua is the first industrial city in the upper reaches of the Yangtze River. The relationship between influenza epidemics and local climatic variables was examined based on regression models. The temporal distribution of influenza subtypes/lineages during the pre-pandemic (2006–2009), pandemic (2009) and post-pandemic (2010–2015) years was described and compared. A total of 6892 respiratory specimens were collected and 737 influenza viruses were isolated. A/H3N2 showed an annual cycle with a peak in summer–autumn, while A/H1N1pdm09, Victoria and Yamagata exhibited an annual cycle with a peak in winter–spring. Regression analyses demonstrated that relative humidity was positively associated with A/H3N2 activity while negatively associated with Victoria activity. Higher prevalence of A/H1N1pdm09 and Yamagata was driven by lower absolute humidity. The role of weather conditions in regulating influenza epidemics could be complicated since the diverse viral transmission modes and mechanism. Differences in seasonality and different associations with meteorological factors by influenza subtypes/lineages should be considered in epidemiological studies in the tropics/subtropics. The development of subtype- and lineage-specific prevention and control measures is of significant importance.
Laser–solid interactions are highly suited as a potential source of high energy X-rays for nondestructive imaging. A bright, energetic X-ray pulse can be driven from a small source, making it ideal for high resolution X-ray radiography. By limiting the lateral dimensions of the target we are able to confine the region over which X-rays are produced, enabling imaging with enhanced resolution and contrast. Using constrained targets we demonstrate experimentally a
X-ray source, improving the image quality compared to unconstrained foil targets. Modelling demonstrates that a larger sheath field envelope around the perimeter of the constrained targets increases the proportion of electron current that recirculates through the target, driving a brighter source of X-rays.
Global inequity in access to and availability of essential mental health services is well recognized. The mental health treatment gap is approximately 50% in all countries, with up to 90% of people in the lowest-income countries lacking access to required mental health services. Increased investment in global mental health (GMH) has increased innovation in mental health service delivery in LMICs. Situational analyses in areas where mental health services and systems are poorly developed and resourced are essential when planning for research and implementation, however, little guidance is available to inform methodological approaches to conducting these types of studies. This scoping review provides an analysis of methodological approaches to situational analysis in GMH, including an assessment of the extent to which situational analyses include equity in study designs. It is intended as a resource that identifies current gaps and areas for future development in GMH. Formative research, including situational analysis, is an essential first step in conducting robust implementation research, an essential area of study in GMH that will help to promote improved availability of, access to and reach of mental health services for people living with mental illness in low- and middle-income countries (LMICs). While strong leadership in this field exists, there remain significant opportunities for enhanced research representing different LMICs and regions.
Laser interaction with an ultra-thin pre-structured target is investigated with the help of both two-dimensional and three-dimensional particle-in-cell simulations. With the existence of a periodic structure on the target surface, the laser seems to penetrate through the target at its fundamental frequency even if the plasma density of the target is much higher than the laser’s relativistically critical density. The particle-in-cell simulations show that the transmitted laser energy behind the pre-structured target is increased by about two orders of magnitude compared to that behind the flat target. Theoretical analyses show that the transmitted energy behind the pre-structured target is actually re-emitted by electron ‘islands’ formed by the surface plasma waves on the target surfaces. In other words, the radiation with the fundamental frequency is actually ‘surface emission’ on the target rear surface. Besides the intensity of the component with the fundamental frequency, the intensity of the high-order harmonics behind the pre-structured target is also much enhanced compared to that behind the flat target. The enhancement of the high-order harmonics is also related to the surface plasma waves generated on the target surfaces.
A multichannel calorimeter system is designed and constructed which is capable of delivering single-shot and broad-band spectral measurement of terahertz (THz) radiation generated in intense laser–plasma interactions. The generation mechanism of backward THz radiation (BTR) is studied by using the multichannel calorimeter system in an intense picosecond laser–solid interaction experiment. The dependence of the BTR energy and spectrum on laser energy, target thickness and pre-plasma scale length is obtained. These results indicate that coherent transition radiation is responsible for the low-frequency component (
1 THz) of BTR. It is also observed that a large-scale pre-plasma primarily enhances the high-frequency component (
3 THz) of BTR.
Cultivated pastures in southern China are being used to improve forage productivity and animal performance, but studies on grazing behaviour of goats in these cultivated pastures are still rare. In the current study, the grazing behaviour of Yunling black goats under low (5 goats/ha) and high (15 goats/ha) stocking rates (SRs) was evaluated. Data showed that the proportion of time goats spent on activities was: eating (0.59–0.87), ruminating (0.05–0.35), walking (0.03–0.06) and resting (0.01–0.03). Compared with low SR, goats spent more time eating and walking, and less time ruminating and resting under high SR. Goats had similar diet preferences under both SR and preferred to eat grasses (ryegrass and cocksfoot) more than a legume (white clover). The distribution of eating time on each forage species was more uniform under high v. low SR. Bites/step, bite weight and daily intake were greater under low than high SR. Results suggest that the SR affects grazing behaviour of goats on cultivated pasture, and identifying an optimal SR is critical for increasing bite weight and intake.
Ischemic stroke treatment is time-sensitive, and barriers to providing prehospital care encountered by Emergency Medical Services (EMS) providers have been under-studied.
This study described barriers to providing prehospital care, identified predictors of these barriers, and assessed the impact of these barriers on EMS on-scene time and administration of tissue plasminogen activator (tPA) in the emergency department (ED).
A retrospective cohort study was performed using the Get With The Guidelines-Stroke (GWTG-S; American Heart Association [AHA]; Dallas, Texas USA) registry at two hospitals to identify ischemic stroke patients arriving by EMS. Variables were abstracted from prehospital and hospital medical records and merged with registry data. Barriers to care were grouped into themes. Logistic regression was used to identify predictors of barriers to care, and bi-variate tests were used to assess differences in EMS on-scene time and the proportion of patients receiving tPA between patients with and without barriers.
Barriers to providing prehospital care were documented for 15.5% of patients: 29.6% related to access, 26.7% communication, 23.0% extrication and transportation, 20.0% refusal, and 14.1% assessment/management. Non-white and non-black race (OR: 3.69; 95% CI, 1.63-8.36) and living alone (OR: 1.53; 95% CI, 1.05-2.23) were associated with greater odds of barriers to providing care. The EMS on-scene time was ≥15 minutes for 70.4% of patients who had a barrier to care, compared with 49.0% of patients who did not (P<.001). There was no significant difference in the proportion of patients who were administered tPA between those with and without barriers to care (14.1% vs 19.2%; P=.159).
Barriers to providing prehospital care were documented for a sizable proportion of ischemic stroke patients, with the majority related to patient access and communication, and occurred more frequently among non-white and non-black patients and those living alone. Although EMS on-scene time was longer for patients with barriers to care, the proportion of patients receiving tPA in the ED did not differ.
LiT, CushmanJT, ShahMN, KellyAG, RichDQ, JonesCMC. Barriers to Providing Prehospital Care to Ischemic Stroke Patients: Predictors and Impact on Care. Prehosp Disaster Med.2018;33(5):501–507.
Background: Acromegaly is associated with significant morbidity. The purpose of this study was to establish characteristics and outcomes of patients treated for acromegaly at The Ottawa Hospital, to compare our results with published reports from other centers and to identify opportunities to improve patient care. Methods: A retrospective chart review of patients surgically and medically treated for acromegaly between January 1, 2007 and December 31, 2016 was completed. Demographic information, biochemical data, presenting features, disease comorbidities, treatment interventions, and were collected. Results: Fifty-one patients were identified using CCI/ICD-10 codes and IGF-1 levels. Similar to other centers, the majority of patients had a macroadenoma (78.4% vs 11.8%) with a high percentage invading the cavernous sinus (57.5%). While surgical intervention was performed in 90% of patients, only 23.3% of patient achieved surgical cure (IGF-1 normalization within reference range). Approximately 30% of patients were controlled with adjuvant medical therapy while more than 40 % had elevated IGF-1 levels at last follow-up. Radiotherapy was less commonly used. Conclusions: Despite a multi-modal treatment approach for acromegaly, outcomes are variable. This study highlights the need for further research to better understand factors associated with surgical cure, response to medical therapy and the role of radiotherapy.
Group-3 medulloblastoma (MBL) is highly resistant to radiation (IR) and chemotherapy and has the worst prognosis. Hence, there is an urgent need to elucidate targets that sensitize these tumors to chemotherapy and IR. Employing standard assays for viability and sensitization to IR, we identified PRDX1 as a therapeutic target in Group-3 MBL. Specifically, targeting PRDX1 by RNAi or inhibition by Adenanthin led to specific killing and sensitization to IR of Group-3 MBL cells. We rescued sensitization of Daoy and UW228 cells by hypermorphic expression of PRDX1. PRDX1 knockdown caused oxidative DNA damage and induced apoptosis. We correlated PRDX1 expression to patient outcomes in a validated MBL tumor-microarray. Whole genome sequencing identified pathways/genes that were dysregulated with PRDX1 inhibition or silencing. Our in vivo studies in mice employing flank/orthotopic tumors from patient derived xenografts/Group-3 MBL cells confirmed in vitro observations. Animals with tumors in which PRDX1 was targeted by RNAi or Adenanthin (using mini osmotic pumps) showed decreased tumor burden and increased survival when compared to controls. Since, Adenanthin does not cross the blood brain barrier (BBB) we used HAV6 peptide to transiently disrupt the BBB and deliver Adenanthin to the tumor. Immunohistochemistry confirmed that targeting PRDX1 resulted in increased oxidative DNA damage, apoptosis and decreased proliferation. In summary, we have validated PRDX1 as a therapeutic target in group-3 MBL, identified Adenanthin as a potent chemical inhibitor of PRDX1 and confirmed the role of HAV peptide (in the transient modulation of BBB permeability) in an orthotopic model of group-3 MBL.