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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 Enenteridae Yamaguti, 1958 and Gyliauchenidae Fukui, 1929 exhibit an interesting pattern of host partitioning in herbivorous fishes of the Indo-West Pacific. Enenterids are known almost exclusively from fishes of the family Kyphosidae, a group of herbivorous marine fishes common on tropical and temperate reefs. In contrast, gyliauchenids are found in most of the remaining lineages of marine herbivorous fishes, but until the present study, had never been known from kyphosids. Here we report on the first species of gyliauchenid known from a kyphosid. Endochortophagus protoporus gen. nov., sp. nov. was recovered from the Western buffalo bream, Kyphosus cornelii (Whitley, 1944), collected off Western Australia. Kyphosus cornelii also hosts an enenterid, Koseiria allanwilliamsi Bray & Cribb, 2002, and is thus the first fish known in which enenterids and gyliauchenids co-occur. Molecular phylogenetic analyses place the new species close to those of Affecauda Hall & Chambers, 1999 and Flagellotrema Ozaki, 1936, but there is sufficient morphological evidence, combined with the unusual host, to consider it distinct from these genera. We discuss factors which may have contributed to the host partitioning pattern observed between enenterids and gyliauchenids.
Background: To determine whether exosomal microRNAs (miRNAs) in CSF of patients with FTD can serve as diagnostic biomarkers, we assessed miRNA expression in the Genetic FTD Initiative (GENFI) cohort and in sporadic FTD. Methods: GENFI participants were either carriers of a pathogenic mutation or at risk of carrying a mutation because a first-degree relative was a symptomatic mutation carrier. Exosomes were isolated from CSF of 23 -pre-symptomatic and 15 symptomatic mutation carriers, and 11 healthy non-mutation carriers. Expression of miRNAs was measured using qPCR arrays. MiRNAs differentially expressed in symptomatic compared to pre-symptomatic mutation carriers were evaluated in 17 patients with sporadic FTD, 13 patients with sporadic Alzheimer’s disease (AD), and 10 healthy controls (HCs). Results: In the GENFI cohort, miR-204-5p and miR-632 were significantly decreased in symptomatic compared to pre-symptomatic mutation carriers. Decrease of miR-204-5p and miR-632 revealed receiver operator characteristics with an area of 0.89 [90% CI: 0.79-0.98] and 0.81 [90% CI: 0.68-0.93], and when combined an area of 0.93 [90% CI: 0.87-0.99]. In sporadic FTD, only miR-632 was significantly decreased compared to sporadic AD and HCs. Decrease of miR-632 revealed an area of 0.89 [90% CI: 0.80-0.98]. Conclusions: Exosomal miR-204-5p and miR-632 have potential as diagnostic biomarkers for genetic FTD and miR-632 also for sporadic FTD.
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.
On August 25, 2017, Hurricane Harvey made landfall near Corpus Christi, Texas. The ensuing unprecedented flooding throughout the Texas coastal region affected millions of individuals.1 The statewide response in Texas included the sheltering of thousands of individuals at considerable distances from their homes. The Dallas area established large-scale general population sheltering as the number of evacuees to the area began to amass. Historically, the Dallas area is one familiar with “mega-sheltering,” beginning with the response to Hurricane Katrina in 2005.2 Through continued efforts and development, the Dallas area had been readying a plan for the largest general population shelter in Texas. (Disaster Med Public Health Preparedness. 2019;13:33–37)
The Arctic marine environment is undergoing a transition from thick multi-year to first-year sea-ice cover with coincident lengthening of the melt season. Such changes are evident in the Baffin Bay-Davis Strait-Labrador Sea (BDL) region where melt onset has occurred ~8 days decade−1 earlier from 1979 to 2015. A series of anomalously early events has occurred since the mid-1990s, overlapping a period of increased upper-air ridging across Greenland and the northwestern North Atlantic. We investigate an extreme early melt event observed in spring 2013. (~6σ below the 1981–2010 melt climatology), with respect to preceding sub-seasonal mid-tropospheric circulation conditions as described by a daily Greenland Blocking Index (GBI). The 40-days prior to the 2013 BDL melt onset are characterized by a persistent, strong 500 hPa anticyclone over the region (GBI >+1 on >75% of days). This circulation pattern advected warm air from northeastern Canada and the northwestern Atlantic poleward onto the thin, first-year sea ice and caused melt ~50 days earlier than normal. The episodic increase in the ridging atmospheric pattern near western Greenland as in 2013, exemplified by large positive GBI values, is an important recent process impacting the atmospheric circulation over a North Atlantic cryosphere undergoing accelerated regional climate change.
Objectives: The aim of this study was to identify whether the three main primary progressive aphasia (PPA) variants would show differential profiles on measures of visuospatial cognition. We hypothesized that the logopenic variant would have the most difficulty across tasks requiring visuospatial and visual memory abilities. Methods: PPA patients (n=156), diagnosed using current criteria, and controls were tested on a battery of tests tapping different aspects of visuospatial cognition. We compared the groups on an overall visuospatial factor; construction, immediate recall, delayed recall, and executive functioning composites; and on individual tests. Cross-sectional and longitudinal comparisons were made, adjusted for disease severity, age, and education. Results: The logopenic variant had significantly lower scores on the visuospatial factor and the most impaired scores on all composites. The nonfluent variant had significant difficulty on all visuospatial composites except the delayed recall, which differentiated them from the logopenic variant. In contrast, the semantic variants performed poorly only on delayed recall of visual information. The logopenic and nonfluent variants showed decline in figure copying performance over time, whereas in the semantic variant, this skill was remarkably preserved. Conclusions: This extensive examination of performance on visuospatial tasks in the PPA variants solidifies some previous findings, for example, delayed recall of visual stimuli adds value in differential diagnosis between logopenic variant PPA and nonfluent variant PPA variants, and illuminates the possibility of common mechanisms that underlie both linguistic and non-linguistic deficits in the variants. Furthermore, this is the first study that has investigated visuospatial functioning over time in the PPA variants. (JINS, 2018, 24, 259–268)
Euthycarcinoid arthropods (Cambrian–Triassic) were likely the first animals to transition from oceanic to freshwater and emergent environments. Although their basic bauplan is well known, they have a poor fossil record because their non-sclerotized exoskeleton was rarely preserved. Euthycarcinoids’ unusual morphology (varying numbers of body segments, seemingly dichotomous possession of either mandibles or a labrum, specialized or generalized limbs, and possession by some euthycarcinoid species of sternal pores—structures possibly analogous to coxal vesicles in myriapods) contribute to uncertainty regarding their relationship to other arthropod groups; while their poor fossil record masks the evolutionary transitions within and between the separate realms they inhabited (marine, freshwater, emergent). A new euthycarcinoid from a Permian polar proglacial lake is described herein that is morphologically unlike all other euthycarcinoids, and interpreted as being well adapted for a nekton-benthic lifestyle. Antarcticarcinus pagoda n. gen. n. sp. possesses a pair of large wing-like processes that project laterally from the preabdominal dorsal exoskeleton. A trace fossil from the overlying Mackellar Formation, cf. Orbiculichnus, which was previously interpreted as having been produced by insects taking off or landing on wet sediments, is reinterpreted herein as being produced by A. pagoda n. gen. n. sp. due to the high degree of morphological similarity between traces and body fossils. This occurrence indicates that euthycarcinoids were able to adapt to life in temperate freshwater environments, while possible subaerial adaptations hint at an ability to breathe air. Indeed, if euthycarcinoids could breathe air, Cambrian terrestrial forays and rapid transition (by the Ordovician) into freshwater environments might be explained.
Intrauterine or fetal growth restriction (IUGR) is a major complication of pregnancy and leads to significant perinatal morbidities and mortality. Typically, induction of IUGR in animals involves the complete occlusion or ablation of vessels to the uterus or placenta, acutely impairing blood flow and fetal growth, usually with high fetal loss. We aimed to produce a model of reduced fetal growth in the spiny mouse with minimal fetal loss. At 27 days gestational age (term is 38–39 days), a piece of silastic tubing was placed around the left uterine artery to prevent the further increase of uterine blood flow with advancing gestation to induce IUGR (occluded). Controls were generated from sham surgeries without placement of the tubing. Dams were humanely euthanized at 37 days gestational age and all fetuses and placentas were weighed and collected. Of the 17 dams that underwent surgery, 15 carried their pregnancies to 37 days gestational age and 95% of fetuses survived to this time. The difference in fetal body weight between occluded and control was ~21% for fetuses in the left uterus side: there were no differences for fetuses in the right uterus side. Offspring from the occluded group had significantly lower brain, liver, lung, kidney and carcass weights compared with shams. Preventing the gestation-related increase of uterine blood flow induced significant growth restriction in the fetal spiny mouse, with minimal fetal loss. This technique could be readily adapted for other small animal.
To assess the burden of bloodstream infections (BSIs) among pediatric hematology-oncology (PHO) inpatients, to propose a comprehensive, all-BSI tracking approach, and to discuss how such an approach helps better inform within-center and across-center differences in CLABSI rate
Prospective cohort study
US multicenter, quality-improvement, BSI prevention network
PHO centers across the United States who agreed to follow a standardized central-line–maintenance care bundle and track all BSI events and central-line days every month.
Infections were categorized as CLABSI (stratified by mucosal barrier injury–related, laboratory-confirmed BSI [MBI-LCBI] versus non–MBI-LCBI) and secondary BSI, using National Healthcare Safety Network (NHSN) definitions. Single positive blood cultures (SPBCs) with NHSN defined common commensals were also tracked.
Between 2013 and 2015, 34 PHO centers reported 1,110 BSIs. Among them, 708 (63.8%) were CLABSIs, 170 (15.3%) were secondary BSIs, and 232 (20.9%) were SPBCs. Most SPBCs (75%) occurred in patients with profound neutropenia; 22% of SPBCs were viridans group streptococci. Among the CLABSIs, 51% were MBI-LCBI. Excluding SPBCs, CLABSI rates were higher (88% vs 77%) and secondary BSI rates were lower (12% vs 23%) after the NHSN updated the definition of secondary BSI (P<.001). Preliminary analyses showed across-center differences in CLABSI versus secondary BSI and between SPBC and CLABSI versus non-CLABSI rates.
Tracking all BSIs, not just CLABSIs in PHO patients, is a patient-centered, clinically relevant approach that could help better assess across-center and within-center differences in infection rates, including CLABSI. This approach enables informed decision making by healthcare providers, payors, and the public.
The Antarctic Roadmap Challenges (ARC) project identified critical requirements to deliver high priority Antarctic research in the 21st century. The ARC project addressed the challenges of enabling technologies, facilitating access, providing logistics and infrastructure, and capitalizing on international co-operation. Technological requirements include: i) innovative automated in situ observing systems, sensors and interoperable platforms (including power demands), ii) realistic and holistic numerical models, iii) enhanced remote sensing and sensors, iv) expanded sample collection and retrieval technologies, and v) greater cyber-infrastructure to process ‘big data’ collection, transmission and analyses while promoting data accessibility. These technologies must be widely available, performance and reliability must be improved and technologies used elsewhere must be applied to the Antarctic. Considerable Antarctic research is field-based, making access to vital geographical targets essential. Future research will require continent- and ocean-wide environmentally responsible access to coastal and interior Antarctica and the Southern Ocean. Year-round access is indispensable. The cost of future Antarctic science is great but there are opportunities for all to participate commensurate with national resources, expertise and interests. The scope of future Antarctic research will necessitate enhanced and inventive interdisciplinary and international collaborations. The full promise of Antarctic science will only be realized if nations act together.
Vancomycin-resistant enterococci (VRE) infections are a public health threat associated with increased patient mortality and healthcare costs. Antibiotic usage, particularly cephalosporins, has been associated with VRE colonization and VRE bloodstream infections (VRE BSI). We examined the relationship between antimicrobial usage and incident VRE colonization at the individual patient level. Prospective, weekly surveillance was undertaken for incident VRE colonization defined by negative admission but positive surveillance swab in a medical intensive care unit over a 17-month period. Antimicrobial exposure was quantified as days of therapy (DOT)/1000 patient-days. Multiple logistic regression was used to analyse incident VRE colonization and antibiotic DOT, controlling for demographic and clinical covariates. Ninety-six percent (1398/1454) of admissions were swabbed within 24 h of intensive care unit (ICU) arrival and of the 380 patients in the ICU long enough for weekly surveillance, 83 (22%) developed incident VRE colonization. Incident colonization was associated in bivariate analysis with male gender, more previous hospital admissions, longer previous hospital stay, and use of cefepime/ceftazidime, fluconazole, azithromycin, and metronidazole (P < 0·05). After controlling for demographic and clinical covariates, metronidazole was the only antibiotic independently associated with incident VRE colonization (odds ratio 2·0, 95% confidence interval 1·2–3·3, P < 0·009). Our findings suggest that risk of incident VRE colonization differs between individual antibiotic agents and support the possibility that antimicrobial stewardship may impact VRE colonization and infection.
Antibiotic treatment for asymptomatic bacteriuria (ASB) is prevalent but often contrary to published guidelines.
To evaluate risk factors for treatment of ASB.
Retrospective observational study.
A tertiary academic hospital, county hospital, and community hospital.
Hospitalized adults with bacteriuria.
Patients without documented symptoms of urinary tract infection per Infectious Diseases Society of America (IDSA) criteria were classified as ASB. We examined ASB treatment risk factors as well as broad-spectrum antibiotic usage and quantified diagnostic concordance between IDSA and National Healthcare Safety Network criteria.
Among 300 patients with bacteriuria, ASB was present in 71% by IDSA criteria. By National Healthcare Safety Network criteria, 71% of patients had ASB; within-patient diagnostic concordance with IDSA was moderate (kappa, 0.52). After excluding those given antibiotics for nonurinary indications, antibiotics were given to 38% (62/164) with ASB. Factors significantly associated with ASB treatment were elevated urine white cell count (65 vs 24 white blood cells per high-powered field, P<.01), hospital identity (hospital C vs A, odds ratio, 0.34 [95% CI, 0.14–0.80], P =.01), presence of leukocyte esterase (5.48 [2.35–12.79], P<.01), presence of nitrites (2.45 [1.11–5.41], P=.03), and Escherichia coli on culture (2.4 [1.2–4.7], P=.01). Of patients treated for ASB, broad-spectrum antibiotics were used in 84%.
ASB treatment was prevalent across settings and contributed to broad-spectrum antibiotic use. Associating abnormal urinalysis results with the need for antibiotic treatment regardless of symptoms may drive unnecessary antibiotic use.
Infect. Control Hosp. Epidemiol. 2016;37(3):319–326
Introduced exotic plants can drive ecosystem change. We studied invasion and establishment of Brassica tournefortii (African mustard), a noxious weed, in the Chemehuevi Valley, western Sonoran Desert, California. We used long-term data sets of photographs, transects for biomass of annual plants, and densities of African mustard collected at irregular intervals between 1979 and 2009. We suggest that African mustard may have been present in low numbers along the main route of travel, a highway, in the late 1970s; invaded the valley along a major axial valley ephemeral stream channel and the highway; and by 2009, colonized 22 km into the eastern part of the valley. We developed predictive models for invasibility and establishment of African mustard. Both during the initial invasion and after establishment, significant predictor variables of African mustard densities were surficial geology, proximity to the highway and axial valley ephemeral stream channel, and number of small ephemeral stream channels. The axial valley ephemeral stream channel was the most vulnerable of the variables to invasions. Overall, African mustard rapidly colonized and quickly became established in naturally disturbed areas, such as stream channels, where geological surfaces were young and soils were weakly developed. Older geological surfaces (e.g., desert pavements with soils 140,000 to 300,000 years old) were less vulnerable. Microhabitats also influenced densities of African mustard, with densities higher under shrubs than in the interspaces. As African mustard became established, the proportional biomass of native winter annual plants declined. Early control is important because African mustard can colonize and become well established across a valley in 20 yr.
In North America, terrestrial records of biodiversity and climate change that span Marine Oxygen Isotope Stage (MIS) 5 are rare. Where found, they provide insight into how the coupling of the ocean–atmosphere system is manifested in biotic and environmental records and how the biosphere responds to climate change. In 2010–2011, construction at Ziegler Reservoir near Snowmass Village, Colorado (USA) revealed a nearly continuous, lacustrine/wetland sedimentary sequence that preserved evidence of past plant communities between ~140 and 55 ka, including all of MIS 5. At an elevation of 2705 m, the Ziegler Reservoir fossil site also contained thousands of well-preserved bones of late Pleistocene megafauna, including mastodons, mammoths, ground sloths, horses, camels, deer, bison, black bear, coyotes, and bighorn sheep. In addition, the site contained more than 26,000 bones from at least 30 species of small animals including salamanders, otters, muskrats, minks, rabbits, beavers, frogs, lizards, snakes, fish, and birds. The combination of macro- and micro-vertebrates, invertebrates, terrestrial and aquatic plant macrofossils, a detailed pollen record, and a robust, directly dated stratigraphic framework shows that high-elevation ecosystems in the Rocky Mountains of Colorado are climatically sensitive and varied dramatically throughout MIS 5.
Antarctic and Southern Ocean science is vital to understanding natural variability, the processes that govern global change and the role of humans in the Earth and climate system. The potential for new knowledge to be gained from future Antarctic science is substantial. Therefore, the international Antarctic community came together to ‘scan the horizon’ to identify the highest priority scientific questions that researchers should aspire to answer in the next two decades and beyond. Wide consultation was a fundamental principle for the development of a collective, international view of the most important future directions in Antarctic science. From the many possibilities, the horizon scan identified 80 key scientific questions through structured debate, discussion, revision and voting. Questions were clustered into seven topics: i) Antarctic atmosphere and global connections, ii) Southern Ocean and sea ice in a warming world, iii) ice sheet and sea level, iv) the dynamic Earth, v) life on the precipice, vi) near-Earth space and beyond, and vii) human presence in Antarctica. Answering the questions identified by the horizon scan will require innovative experimental designs, novel applications of technology, invention of next-generation field and laboratory approaches, and expanded observing systems and networks. Unbiased, non-contaminating procedures will be required to retrieve the requisite air, biota, sediment, rock, ice and water samples. Sustained year-round access to Antarctica and the Southern Ocean will be essential to increase winter-time measurements. Improved models are needed that represent Antarctica and the Southern Ocean in the Earth System, and provide predictions at spatial and temporal resolutions useful for decision making. A co-ordinated portfolio of cross-disciplinary science, based on new models of international collaboration, will be essential as no scientist, programme or nation can realize these aspirations alone.