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The Fontan Outcomes Network was created to improve outcomes for children and adults with single ventricle CHD living with Fontan circulation. The network mission is to optimise longevity and quality of life by improving physical health, neurodevelopmental outcomes, resilience, and emotional health for these individuals and their families. This manuscript describes the systematic design of this new learning health network, including the initial steps in development of a national, lifespan registry, and pilot testing of data collection forms at 10 congenital heart centres.
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.
In Canada, recreational use of cannabis was legalized in October 2018. This policy change along with recent publications evaluating the efficacy of cannabis for the medical treatment of epilepsy and media awareness about its use have increased the public interest about this agent. The Canadian League Against Epilepsy Medical Therapeutics Committee, along with a multidisciplinary group of experts and Canadian Epilepsy Alliance representatives, has developed a position statement about the use of medical cannabis for epilepsy. This article addresses the current Canadian legal framework, recent publications about its efficacy and safety profile, and our understanding of the clinical issues that should be considered when contemplating cannabis use for medical purposes.
Immune system markers may predict affective disorder treatment response, but whether an overall immune system marker predicts bipolar disorder treatment effect is unclear.
Bipolar CHOICE (N = 482) and LiTMUS (N = 283) were similar comparative effectiveness trials treating patients with bipolar disorder for 24 weeks with four different treatment arms (standard-dose lithium, quetiapine, moderate-dose lithium plus optimised personalised treatment (OPT) and OPT without lithium). We performed secondary mixed effects linear regression analyses adjusted for age, gender, smoking and body mass index to investigate relationships between pre-treatment white blood cell (WBC) levels and clinical global impression scale (CGI) response.
Compared to participants with WBC counts of 4.5–10 × 109/l, participants with WBC < 4.5 or WBC ≥ 10 showed similar improvement within each specific treatment arm and in gender-stratified analyses.
An overall immune system marker did not predict differential treatment response to four different treatment approaches for bipolar disorder all lasting 24 weeks.
Breakthrough Listen is a 10-yr initiative to search for signatures of technologies created by extraterrestrial civilisations at radio and optical wavelengths. Here, we detail the digital data recording system deployed for Breakthrough Listen observations at the 64-m aperture CSIRO Parkes Telescope in New South Wales, Australia. The recording system currently implements two modes: a dual-polarisation, 1.125-GHz bandwidth mode for single-beam observations, and a 26-input, 308-MHz bandwidth mode for the 21-cm multibeam receiver. The system is also designed to support a 3-GHz single-beam mode for the forthcoming Parkes ultra-wideband feed. In this paper, we present details of the system architecture, provide an overview of hardware and software, and present initial performance results.
To assess variability in antimicrobial use and associations with infection testing in pediatric ventilator-associated events (VAEs).
Descriptive retrospective cohort with nested case-control study.
Pediatric intensive care units (PICUs), cardiac intensive care units (CICUs), and neonatal intensive care units (NICUs) in 6 US hospitals.
Children≤18 years ventilated for≥1 calendar day.
We identified patients with pediatric ventilator-associated conditions (VACs), pediatric VACs with antimicrobial use for≥4 days (AVACs), and possible ventilator-associated pneumonia (PVAP, defined as pediatric AVAC with a positive respiratory diagnostic test) according to previously proposed criteria.
Among 9,025 ventilated children, we identified 192 VAC cases, 43 in CICUs, 70 in PICUs, and 79 in NICUs. AVAC criteria were met in 79 VAC cases (41%) (58% CICU; 51% PICU; and 23% NICU), and varied by hospital (CICU, 20–67%; PICU, 0–70%; and NICU, 0–43%). Type and duration of AVAC antimicrobials varied by ICU type. AVAC cases in CICUs and PICUs received broad-spectrum antimicrobials more often than those in NICUs. Among AVAC cases, 39% had respiratory infection diagnostic testing performed; PVAP was identified in 15 VAC cases. Also, among AVAC cases, 73% had no associated positive respiratory or nonrespiratory diagnostic test.
Antimicrobial use is common in pediatric VAC, with variability in spectrum and duration of antimicrobials within hospitals and across ICU types, while PVAP is uncommon. Prolonged antimicrobial use despite low rates of PVAP or positive laboratory testing for infection suggests that AVAC may provide a lever for antimicrobial stewardship programs to improve utilization.
The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.
Modern high-throughput molecular and analytical tools offer exciting opportunities to gain a mechanistic understanding of unique traits of weeds. During the past decade, tremendous progress has been made within the weed science discipline using genomic techniques to gain deeper insights into weedy traits such as invasiveness, hybridization, and herbicide resistance. Though the adoption of newer “omics” techniques such as proteomics, metabolomics, and physionomics has been slow, applications of these omics platforms to study plants, especially agriculturally important crops and weeds, have been increasing over the years. In weed science, these platforms are now used more frequently to understand mechanisms of herbicide resistance, weed resistance evolution, and crop–weed interactions. Use of these techniques could help weed scientists to further reduce the knowledge gaps in understanding weedy traits. Although these techniques can provide robust insights about the molecular functioning of plants, employing a single omics platform can rarely elucidate the gene-level regulation and the associated real-time expression of weedy traits due to the complex and overlapping nature of biological interactions. Therefore, it is desirable to integrate the different omics technologies to give a better understanding of molecular functioning of biological systems. This multidimensional integrated approach can therefore offer new avenues for better understanding of questions of interest to weed scientists. This review offers a retrospective and prospective examination of omics platforms employed to investigate weed physiology and novel approaches and new technologies that can provide holistic and knowledge-based weed management strategies for future.
Leafy spurge (Euphorbia esula L.) is an invasive perennial weed infesting range and recreational lands of North America. Previous research and omics projects with E. esula have helped develop it as a model for studying many aspects of perennial plant development and response to abiotic stress. However, the lack of an assembled genome for E. esula has limited the power of previous transcriptomics studies to identify functional promoter elements and transcription factor binding sites. An assembled genome for E. esula would enhance our understanding of signaling processes controlling plant development and responses to environmental stress and provide a better understanding of genetic factors impacting weediness traits, evolution, and herbicide resistance. A comprehensive transcriptome database would also assist in analyzing future RNA-seq studies and is needed to annotate and assess genomic sequence assemblies. Here, we assembled and annotated 56,234 unigenes from an assembly of 589,235 RNA-seq-derived contigs and a previously published Sanger-sequenced expressed sequence tag collection. The resulting data indicate that we now have sequence for >90% of the expressed E. esula protein-coding genes. We also assembled the gene space of E. esula by using a limited coverage (18X) genomic sequence database. In this study, the programs Velvet and Trinity produced the best gene-space assemblies based on representation of expressed and conserved eukaryotic genes. The results indicate that E. esula contains as much as 23% repetitive sequences, of which 11% are unique. Our sequence data were also sufficient for assembling a full chloroplast and partial mitochondrial genome. Further, marker analysis identified more than 150,000 high-quality variants in our E. esula L-RNA–scaffolded, whole-genome, Trinity-assembled genome. Based on these results, E. esula appears to have limited heterozygosity. This study provides a blueprint for low-cost genomic assemblies in weed species and new resources for identifying conserved and novel promoter regions among coordinately expressed genes of E. esula.
The History, Electrocardiogram (ECG), Age, Risk Factors, and Troponin (HEART) score is a decision aid designed to risk stratify emergency department (ED) patients with acute chest pain. It has been validated for ED use, but it has yet to be evaluated in a prehospital setting.
A prehospital modified HEART score can predict major adverse cardiac events (MACE) among undifferentiated chest pain patients transported to the ED.
A retrospective cohort study of patients with chest pain transported by two county-based Emergency Medical Service (EMS) agencies to a tertiary care center was conducted. Adults without ST-elevation myocardial infarction (STEMI) were included. Inter-facility transfers and those without a prehospital 12-lead ECG or an ED troponin measurement were excluded. Modified HEART scores were calculated by study investigators using a standardized data collection tool for each patient. All MACE (death, myocardial infarction [MI], or coronary revascularization) were determined by record review at 30 days. The sensitivity and negative predictive values (NPVs) for MACE at 30 days were calculated.
Over the study period, 794 patients met inclusion criteria. A MACE at 30 days was present in 10.7% (85/794) of patients with 12 deaths (1.5%), 66 MIs (8.3%), and 12 coronary revascularizations without MI (1.5%). The modified HEART score identified 33.2% (264/794) of patients as low risk. Among low-risk patients, 1.9% (5/264) had MACE (two MIs and three revascularizations without MI). The sensitivity and NPV for 30-day MACE was 94.1% (95% CI, 86.8-98.1) and 98.1% (95% CI, 95.6-99.4), respectively.
Prehospital modified HEART scores have a high NPV for MACE at 30 days. A study in which prehospital providers prospectively apply this decision aid is warranted.
Low-density, highly porous graphene/graphene oxide (GO) based-foams have shown high performance in energy absorption applications, even under high compressive deformations. In general, foams are very effective as energy dissipative materials and have been widely used in many areas such as automotive, aerospace and biomedical industries. In the case of graphene-based foams, the good mechanical properties are mainly attributed to the intrinsic graphene and/or GO electronic and mechanical properties. Despite the attractive physical properties of graphene/GO based-foams, their structural and thermal stabilities are still a problem for some applications. For instance, they are easily degraded when placed in flowing solutions, either by the collapsing of their layers or just by structural disintegration into small pieces. Recently, a new and scalable synthetic approach to produce low-density 3D macroscopic GO structure interconnected with polydimethylsiloxane (PDMS) polymeric chains (pGO) was proposed. A controlled amount of PDMS is infused into the freeze-dried foam resulting into a very rigid structure with improved mechanical properties, such as tensile plasticity and toughness. The PDMS wets the graphene oxide sheets and acts like a glue bonding PDMS and GO sheets. In order to obtain further insights on mechanisms behind the enhanced mechanical pGO response we carried out fully atomistic molecular dynamics (MD) simulations. Based on MD results, we build up a structural model that can explain the experimentally observed mechanical behavior.
The discovery of the first electromagnetic counterpart to a gravitational wave signal has generated follow-up observations by over 50 facilities world-wide, ushering in the new era of multi-messenger astronomy. In this paper, we present follow-up observations of the gravitational wave event GW170817 and its electromagnetic counterpart SSS17a/DLT17ck (IAU label AT2017gfo) by 14 Australian telescopes and partner observatories as part of Australian-based and Australian-led research programs. We report early- to late-time multi-wavelength observations, including optical imaging and spectroscopy, mid-infrared imaging, radio imaging, and searches for fast radio bursts. Our optical spectra reveal that the transient source emission cooled from approximately 6 400 K to 2 100 K over a 7-d period and produced no significant optical emission lines. The spectral profiles, cooling rate, and photometric light curves are consistent with the expected outburst and subsequent processes of a binary neutron star merger. Star formation in the host galaxy probably ceased at least a Gyr ago, although there is evidence for a galaxy merger. Binary pulsars with short (100 Myr) decay times are therefore unlikely progenitors, but pulsars like PSR B1534+12 with its 2.7 Gyr coalescence time could produce such a merger. The displacement (~2.2 kpc) of the binary star system from the centre of the main galaxy is not unusual for stars in the host galaxy or stars originating in the merging galaxy, and therefore any constraints on the kick velocity imparted to the progenitor are poor.
Early Archaic human skeletal remains found in a burial context in Lapa do
Santo in east-central Brazil provide a rare glimpse into the lives of
hunter-gatherer communities in South America, including their rituals for
dealing with the dead. These included the reduction of the body by means of
mutilation, defleshing, tooth removal, exposure to fire and possibly
cannibalism, followed by the secondary burial of the remains according to
strict rules. In a later period, pits were filled with disarticulated bones
of a single individual without signs of body manipulation, demonstrating
that the region was inhabited by dynamic groups in constant transformation
over a period of centuries.
The Dark Energy Survey is undertaking an observational programme imaging 1/4 of the southern hemisphere sky with unprecedented photometric accuracy. In the process of observing millions of faint stars and galaxies to constrain the parameters of the dark energy equation of state, the Dark Energy Survey will obtain pre-discovery images of the regions surrounding an estimated 100 gamma-ray bursts over 5 yr. Once gamma-ray bursts are detected by, e.g., the Swift satellite, the DES data will be extremely useful for follow-up observations by the transient astronomy community. We describe a recently-commissioned suite of software that listens continuously for automated notices of gamma-ray burst activity, collates information from archival DES data, and disseminates relevant data products back to the community in near-real-time. Of particular importance are the opportunities that non-public DES data provide for relative photometry of the optical counterparts of gamma-ray bursts, as well as for identifying key characteristics (e.g., photometric redshifts) of potential gamma-ray burst host galaxies. We provide the functional details of the DESAlert software, and its data products, and we show sample results from the application of DESAlert to numerous previously detected gamma-ray bursts, including the possible identification of several heretofore unknown gamma-ray burst hosts.
This study investigated comparatively the pathogenicity of experimental infection of mice and guinea pigs, with Angiostrongylus mackerrasae and the closely related species A. cantonensis. Time course analyses showed that A. mackerrasae causes eosinophilic meningitis in these hosts, which suggests that the species has the potential to cause meningitis in humans and domestic animals. Both A. mackerrasae and the genetically similar A. cantonensis caused eosinophilic meningitis in mice at two time points of 14 and 21 days post infection (dpi). The brain lesions in mice infected with A. mackerrasae were more granulomatous in nature and the parasites were more likely to appear degenerate compared with lesions caused by A. cantonensis. This may indicate that the mouse immune system eliminates A. mackerrasae infection more effectively. The immunologic responses of mice infected with the two Angiostrongylus species was compared by assessing ex vivo stimulated spleen derived T cells and cytokines including interferon-gamma, interleukin 4 and interleukin 17 on 14 and 21 dpi. The results were similar for mice infected with A. cantonensis and A. mackerrasae. Serum from the infected animals with either A. cantonensis or A. mackerrasae recognized total soluble antigen of A. cantonensis female worms on Western blot.
Recommended rates of glyphosate for noncultivated areas destroy the
aboveground shoots of the perennial plant leafy spurge. However, such
applications cause little or no damage to underground adventitious buds
(UABs), and thus the plant readily regenerates vegetatively. High
concentrations of glyphosate, applied under controlled environmental
conditions, have been shown to cause sublethal effects in UABs of leafy
spurge that produce stunted and bushy phenotypes in subsequent generations
of shoots. We treated leafy spurge plants in the field with glyphosate (0,
1.1, 3.4, or 6.7 kg ai ha−1) to determine its effects on
vegetative growth from UABs and on molecular processes. The number of shoots
derived from UABs of glyphosate-treated plants was significantly increased
compared to controls in subsequent years after application, and new shoots
displayed various phenotypical changes, such as stunted and bushy
phenotypes. Quantifying the abundance of a selected set of transcripts in
UABs of nontreated vs. treated plants (0 vs. 6.7 kg ha−1)
indicated that glyphosate impacted molecular processes involved in
biosynthesis or signaling of tryptophan or auxin (ARF4,
CYP79B2, PIN3, TAA1,
TRP6, YUC4), gibberellic acid
(GA1/CPS1, GA2/KS), ethylene
(ACO1, ACS10), cytokinins
(AHP1, AK2, CKX1), and
the cell cycle (CDC2A, CDC2B,
CYCD3;1). Glyphosate-induced effects on vegetative
growth and transcript abundance were persistent for at least 2 yr after
treatment. Determining the molecular mechanisms associated with vegetative
reproduction in leafy spurge following foliar glyphosate-treatment could
identify limiting factors or new targets for manipulation of plant growth
and development in perennial weeds.
Alligatorweed is a perennial, invasive weed in southern United States rice production, but knowledge on effective management of this weed is limited, especially in conventional (non-imidazolinone-resistant) rice fields. Field studies were conducted in multiple environments in southeastern Texas to evaluate different herbicide options involving penoxsulam, propanil, triclopyr, halosulfuron, bispyribac-sodium, bensulfuron, and quinclorac for alligatorweed control in conventional drill-seeded rice when applied at early POST (EPOST), late POST (LPOST), or both. Among the herbicide options evaluated, penoxsulam alone (up to 83%), penoxsulam plus triclopyr (up to 87%), or bispyribac-sodium plus triclopyr (92%) provided superior alligatorweed control. Plots treated with penoxsulam plus triclopyr EPOST produced the highest yields (9,550 kg ha−1), which were comparable to plots receiving penoxsulam plus triclopyr LPOST (9,320 kg ha−1), penoxsulam alone EPOST (9,280 kg ha−1), and penoxsulam plus halosulfuron LPOST (9,180 kg ha−1). Considering both weed control and rice grain yields, penoxsulam plus triclopyr applied EPOST was found to be the best option among the treatments tested. The treatments bensulfuron alone, bensulfuron plus propanil, penoxsulam plus propanil, triclopyr plus propanil, and bispyribac-sodium plus propanil provided poor (≤ 65%) alligatorweed control. Results also suggest the likelihood for antagonistic interactions when tank-mix combinations tested in this study included propanil.
The Spacewatch Project uses four telescopes of apertures 0.9-m, 1.8-m, 2.3-m, and 4-m on Kitt Peak mountain in Arizona for followup astrometry of priority NEOs. Objects as faint as V=23 on the MPC's NEO Confirmation Page, targets of radar, potential impactors, targets of spacecraft observations or visits, and PHAs with future close approaches to Earth receive priority for astrometry.