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Author: David Edwards (652)


Feb
2018

Arterial wall dynamics arise from the synergy of passive mechano-elastic properties of the vascular tissue and the active contractile behaviour of smooth muscle cells (SMCs) that form the media layer of vessels. We have developed a computational framework that incorporates both these components to account for vascular responses to mechanical and pharmacological stimuli. To validate the proposed framework and demonstrate its potential for testing hypotheses on the pathogenesis of vascular disease, we have employed a number of pharmacological probes that modulate the arterial wall contractile machinery by selectively inhibiting a range of intracellular signalling pathways.

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Feb
2018

Excessive alcohol consumption is associated with a substantial number of emergency department visits annually and is responsible for a significant number of lives lost each year in the United States. However, a minimal amount is known about the impact of alcohol on the EMS system.
The primary objective was to determine the proportion of 9-1-1 calls in Denver, Colorado in which (1) alcohol was a contributing factor or (2) the individual receiving EMS services had recently ingested alcohol.

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Jan
2018

The Developing Human Connectome Project (dHCP) seeks to create the first 4-dimensional connectome of early life. Understanding this connectome in detail may provide insights into normal as well as abnormal patterns of brain development. Following established best practices adopted by the WU-MINN Human Connectome Project (HCP), and pioneered by FreeSurfer, the project utilises cortical surface-based processing pipelines.

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Jan
2018

Individual cells in an organism are variable, which strongly impacts cellular processes. Advances in sequencing technologies have enabled single-cell genomic analysis to become widespread, addressing shortcomings of analyses conducted on populations of bulk cells. While the field of single-cell plant genomics is in its infancy, there is great potential to gain insights into cell lineage and functional cell types to help understand complex cellular interactions in plants.

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Jan
2018

In the past decade, the application of high-throughput sequencing to crop genotyping has given rise to novel platforms capable of genotyping tens of thousands of genome-wide DNA markers. Coupled with the decreasing costs of sequencing, this rapid increase in markers allows accelerated and highly accurate genotyping of entire crop populations and diversity sets using single nucleotide polymorphisms (SNPs). These revolutionary advances accelerate crop improvement by facilitating a more precise connection of phenotype to genotype through association studies, linkage mapping and diversity analysis.

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Jan
2018

This first pan-Mediterranean analysis of genetic diversity in wild narrow-leafed lupin revealed strong East-West genetic differentiation of populations, an historic eastward migration, and signatures of genetic adaptation to climatic variables. Most grain crops suffer from a narrow genetic base, which limits their potential for adapting to new challenges such as increased stresses associated with climate change. Plant breeders are returning to the wild ancestors of crops and their close relatives to broaden the genetic base of their crops.

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Jan
2018

Stress describes the physiological reaction to threat or pressure, which manifests as physical symptoms of exhaustion or energy loss and psychological symptoms, including irritability or tension. If untreated, chronic stress or burnout may develop, both are areas of unmet medical need. Evidence-based treatment and prevention measures are needed.

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Dec
1969

The public health threat posed by a looming 'post-antibiotic' era necessitates new approaches to antibiotic discovery. Drug development has typically avoided exploitation of membrane-binding properties, in contrast to nature's control of biological pathways via modulation of membrane-associated proteins and membrane lipid composition. Here, we describe the rejuvenation of the glycopeptide antibiotic vancomycin via selective targeting of bacterial membranes.

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Jan
2018

The growing human population and a changing environment have raised significant concern for global food security, with the current improvement rate of several important crops inadequate to meet future demand. This slow improvement rate is attributed partly to the long generation times of crop plants. Here, we present a method called 'speed breeding', which greatly shortens generation time and accelerates breeding and research programmes.

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Dec
1969

Preterm infants are at high risk of diffuse white matter injury and adverse neurodevelopmental outcome. The multiple hit hypothesis suggests that the risk of white matter injury increases with cumulative exposure to multiple perinatal risk factors. Our aim was to test this hypothesis in a large cohort of preterm infants using diffusion weighted magnetic resonance imaging (dMRI).

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Dec
2017

Preterm infants show abnormal structural and functional brain development, and have a high risk of long-term neurocognitive problems. The molecular and cellular mechanisms involved are poorly understood, but novel methods now make it possible to address them by examining the relationship between common genetic variability and brain endophenotype. We addressed the hypothesis that variability in the Peroxisome Proliferator Activated Receptor (PPAR) pathway would be related to brain development.

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Dec
2017

Homoeologous exchanges (HEs) have been shown to generate novel gene combinations and phenotypes in a range of polyploid species. Gene presence/absence variation (PAV) is also a major contributor to genetic diversity. In this study, we show that there is an association between these two events, particularly in recent Brassica napus synthetic accessions, and that these represent a novel source of genetic diversity, which can be captured for the improvement of this important crop species.

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Dec
2017

Testosterone deficiency (TD) is an increasingly common problem with significant health implications, but its diagnosis and management can be challenging.
To review the available literature on TD and provide evidence-based statements for UK clinical practice.
Evidence was derived from Medline, EMBASE, and Cochrane searches on hypogonadism, testosterone (T) therapy, and cardiovascular safety from May 2005 to May 2015.

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Dec
2017

Many animal models of disease are suboptimal in their representation of human diseases and lack of predictive power in the success of pivotal human trials. In the context of repurposing drugs with known human safety, it is sometimes appropriate to conduct the "last experiment first," that is, progressing directly to human investigations. However, there are not accepted criteria for when to proceed straight to humans to test a new indication.

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Feb
2018

Resistance to antimicrobials is a growing problem in both developed and developing countries. In nations where AIDS is most prevalent, the human fungal pathogenis a significant contributor to mortality, and its growing resistance to current antifungals is an ever-expanding threat. We investigated octapeptin C4, from the cationic cyclic lipopeptide class of antimicrobials, as a potential new antifungal.

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Mar
2018

Pharmaceutical aerosols are used to treat many pulmonary diseases. The use of low-density powders has proven useful to support efficient drug delivery. Measurements must account for the low-density, spherical particle features contributing to aerodynamic behavior.

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Feb
2018

Crayfish extract information from chemical stimuli during social interactions. Commercial fertilizers increase background ammonia concentrations which may interfere with chemical communication. Background pollution can disrupt perception of chemical stimuli in three ways: masking, sensory impairment, physiological impairment or in combination.

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Feb
2018

Since 2012, Ontario pharmacists have been authorized to administer the influenza vaccine. In April 2016, the Ontario College of Pharmacists (OCP) proposed to expand the Pharmacy Act to allow pharmacists to vaccinate against 13 additional conditions. The OCP held an online public consultation and invited pharmacists, members of the public and organizations to weigh in on the proposed changes.

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Nov
2017

Neurodevelopmental impairment is the most common comorbidity associated with complex congenital heart disease (CHD), while the underlying biological mechanism remains unclear. We hypothesised that impaired cerebral oxygen delivery in infants with CHD is a cause of impaired cortical development, and predicted that cardiac lesions most associated with reduced cerebral oxygen delivery would demonstrate the greatest impairment of cortical development. We compared 30 newborns with complex CHD prior to surgery and 30 age-matched healthy controls using brain MRI.

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Nov
2017

Cardiovascular disease is the leading cause of mortality in Chronic Kidney Disease (CKD). Mitochondrial dysfunction secondary to CKD is a potential source of oxidative stress that may impair vascular function. This study sought to determine if mitochondria derived reactive oxygen species contribute to microvascular dysfunction in Stage 3-5 CKD.

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Jun
2017

EMBL Australia Bioinformatics Resource (EMBL-ABR) is a developing national research infrastructure, providing bioinformatics resources and support to life science and biomedical researchers in Australia. EMBL-ABR comprises 10 geographically distributed national nodes with one coordinating hub, with current funding provided through Bioplatforms Australia and the University of Melbourne for its initial 2-year development phase. The EMBL-ABR mission is to: (1) increase Australia's capacity in bioinformatics and data sciences; (2) contribute to the development of training in bioinformatics skills; (3) showcase Australian data sets at an international level and (4) enable engagement in international programs.

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Nov
2017

There has been a recent proliferation in neuroimaging research focusing on brain development in the prenatal, neonatal and very early childhood brain. Early brain injury and preterm birth are associated with increased risk of neurodevelopmental disorders, indicating the importance of this early period for later outcome.
Although using a wide range of different methodologies and investigating diverse samples, the common aim of many of these studies has been to both track normative development and investigate deviations in this development to predict behavioural, cognitive and neurological function in childhood.

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Oct
2017

In brain imaging, accurate alignment of cortical surfaces is fundamental to the statistical sensitivity and spatial localisation of group studies, and cortical surface-based alignment has generally been accepted to be superior to volume-based approaches at aligning cortical areas. However, human subjects have considerable variation in cortical folding, and in the location of functional areas relative to these folds. This makes alignment of cortical areas a challenging problem.

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Oct
2017

Declining national rates of current tobacco use to an all-time low of 15.1% represents a public health victory. Undermining this progress, however, are smoking rates of up to 50% among high-risk, low-income populations.

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Dec
1969

Tropical rainforests are subject to extensive degradation by commercial selective logging. Despite pervasive changes to forest structure, selectively logged forests represent vital refugia for global biodiversity. The ability of these forests to buffer temperature-sensitive species from climate warming will be an important determinant of their future conservation value, although this topic remains largely unexplored.

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Dec
2017

Plant genome diversity varies from single nucleotide polymorphisms to large-scale deletions, insertions, duplications, or re-arrangements. These re-arrangements of sequences resulting from duplication, gains or losses of DNA segments are termed copy number variations (CNVs). During the last decade, numerous studies have emphasized the importance of CNVs as a factor affecting human phenotype; in particular, CNVs have been associated with risks for several severe diseases.

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Oct
2017

Temperature is a core component of a species' fundamental niche. At the fine scale over which most organisms experience climate (mm to ha), temperature depends upon the amount of radiation reaching the Earth's surface, which is principally governed by vegetation. Tropical regions have undergone widespread and extreme changes to vegetation, particularly through the degradation and conversion of rainforests.

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Oct
2017

Preterm infants who develop neurodevelopmental impairment do not always have recognized abnormalities on cerebral ultrasound, a modality routinely used to assess prognosis. In a high proportion of infants, MRI detects punctate white matter lesions that are not seen on ultrasonography. To determine the relation of punctate lesions to brain development and early neurodevelopmental outcome we used multimodal brain MRI to study a large cohort of preterm infants.

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Dec
1969

Concussion is a worldwide issue in sports medicine at present, and in recent years has evolved into a major consideration for sports in the United Kingdom (UK). Governing bodies, sports clinicians, and indeed athletes themselves are dealing with the implications that this injury brings. In parallel with this, innovative means of managing this condition are emerging.

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Jan
2018

We tested the hypothesis that routine MRI would improve the care and well-being of preterm infants and their families.
Parallel-group randomised trial (1.1 allocation; intention-to-treat) with nested diagnostic and cost evaluations (EudraCT 2009-011602-42).

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Dec
2017

Preoperative ordering of blood products has been an area of optimization due to considerable variability among physicians; overpreparation can lead to extra costs and underpreparation of blood can potentially compromise patient safety.
We examined the potential cost savings of extending the storage interval of a presurgical type-and-screen sample from 7 to 14 days, thereby reducing the need for a new specimen on the day of surgery.
Sensitivity analysis showed annual cost savings for our institution to be an estimated $38,770 ($22,420-$73,120).

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Dec
1969

Mitigating methane production by ruminants is a significant challenge to global livestock production. This research offers a new paradigm to reduce methane emissions from ruminants by breeding climate-clever clovers. We demonstrate wide genetic diversity for the trait methanogenic potential in Australia's key pasture legume, subterranean clover (L.

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Dec
1969

The genomics revolution brought on by advances in high-throughput sequencing has led to the production of vast amounts of data. Databases play an essential role in storing and managing this information to make it available to researchers and crop breeders. This chapter provides an outline of how to use databases and tools for wheat genome research.

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Dec
1969

There is a need to accelerate crop improvement by introducing alleles conferring host plant resistance, abiotic stress adaptation, and high yield potential. Elite cultivars, landraces and wild relatives harbor useful genetic variation that needs to be more easily utilized in plant breeding. We review genome-wide approaches for assessing and identifying alleles associated with desirable agronomic traits in diverse germplasm pools of cereals and legumes.

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Sep
2017

Electroencephalographic recordings from the developing human brain are characterized by spontaneous neuronal bursts, the most common of which is the delta brush. Although similar events in animal models are known to occur in areas of immature cortex and drive their development, their origin in humans has not yet been identified. Here, we use simultaneous EEG-fMRI to localise the source of delta brush events in 10 preterm infants aged 32-36 postmenstrual weeks.

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Oct
2017

Minocycline is under investigation as a neurovascular protective agent for stroke. This study evaluated the pharmacokinetic, anti-inflammatory, and safety profile of minocycline after intracerebral hemorrhage.
This study was a single-site, randomized controlled trial of minocycline conducted from 2013 to 2016.

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Dec
1969

Preterm birth places infants in an adverse environment that leads to abnormal brain development and cerebral injury through a poorly understood mechanism known to involve neuroinflammation. In this study, we integrate human and mouse molecular and neuroimaging data to investigate the role of microglia in preterm white matter damage. Using a mouse model where encephalopathy of prematurity is induced by systemic interleukin-1β administration, we undertake gene network analysis of the microglial transcriptomic response to injury, extend this by analysis of protein-protein interactions, transcription factors and human brain gene expression, and translate findings to living infants using imaging genomics.

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Dec
1969

3-(3-Morpholinopropyl)-7,8-dihydro-6-indeno[5,6-][1,2,4]triazine 1,4-dioxide (SN30- 000), an analog of the well-studied bioreductive prodrug tirapazamine (TPZ), has improved activity against hypoxic cells in tumor xenografts. However, little is known about its biotransformation in normal tissues. Here, we evaluate implications of biotransformation of SN30000 for its toxicokinetics in NIH-III mice.

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Oct
2017

High dietary sodium intake can lead to hypertension and increased incidence of cardiovascular disease. We sought to determine the effect of short-term dietary sodium loading on central blood pressure and arterial stiffness in young (YG; 22-40 years) and middle-aged (MA; 41-60 years) normotensive adults. YG (n = 49; age: 27 ± 1 years) and MA (n = 36; age: 52 ± 1 years) subjects were randomized, in a cross-over design, to 7 days of low-sodium (LS; 20 mmol/d) or high-sodium (HS; 300 mmol/d) diet.

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Dec
2017

Blood pressure responses to dietary sodium vary widely person-to-person. Salt sensitive rodent models display altered autonomic function, a trait thought to contribute to poor cardiovascular health. Thus, we hypothesized that increased salt sensitivity (SS) in normotensive humans would be associated with increased muscle sympathetic nerve activity (MSNA), decreased high frequency heart rate variability (HF-HRV), and decreased baroreflex sensitivity.

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Oct
2017

Globally it is assumed that high-intensity activities are the general cause of fatigue experienced during a soccer match. However, little is known about the hormonal and psychological effects of fatigue due to these activities on semi-professional female soccer players. Forty-seven female players (22.

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Jul
2017

In this study the authors determined the extent of cellular infiltration and dispersion, and regional vascularization in electrophysiologically (EP) defined zones in post-myocardial infarction (MI) swine ventricle.
The critical isthmus (CI) in post-MI re-entrant ventricular tachycardia (VT) is a target for catheter ablation. In vitro evidence suggests that myofibroblasts (MFB) within the scar border zone (BZ) may increase the susceptibility to slow conduction and VT, but whether this occurs in vivo remains unproven.

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Oct
2017

Optical biosensors are often used to measure kinetic rate constants associated with chemical reactions. Such instruments operate in the surface-volume configuration, in which ligand molecules are convected through a fluid-filled volume over a surface to which receptors are confined. Currently, scientists are using optical biosensors to measure the kinetic rate constants associated with DNA translesion synthesis-a process critical to DNA damage repair.

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Aug
2017

Studies exploring parents' trial experiences generally relate to their understanding of the consent process and the development of researcher strategies to facilitate recruitment and retention. The aim was to better understand parents' experience of being part of a trial at the time and their perceptions of trial participation in retrospect.
Data were collected in a number of ways: from recorded discussions between parents and clinicians about the MRI or ultrasound, in open-text responses to questionnaires and in qualitative interviews at 1 and 2 years after participation.

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Nov
2017

Contents 682 I. 682 II. 683 III.

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Aug
2017

Premature birth is associated with numerous complex abnormalities of white and gray matter and a high incidence of long-term neurocognitive impairment. An integrated understanding of these abnormalities and their association with clinical events is lacking. The aim of this study was to identify specific patterns of abnormal cerebral development and their antenatal and postnatal antecedents.

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Mar
2018

Receptor heterogeneity in optical biosensors.

J Math Biol 2018 Mar 13;76(4):795-816. Epub 2017 Jul 13.
Ryan M Evans, David A Edwards
Scientists measure rate constants associated with biochemical reactions in an optical biosensor-an instrument in which ligand molecules are convected through a flow cell over a surface to which receptors are immobilized. We quantify transport effects on such reactions by modeling the associated convection-diffusion equation with a reaction boundary condition. In experimental situations, the full PDE model reduces to a set of unwieldy integrodifferential equations (IDEs).

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Jul
2017

SRA737 is an orally active small-molecule inhibitor of checkpoint kinase 1 being investigated in an oncology setting. A HPLC-MS/MS method for quantifying plasma concentrations of SRA737 was validated.
Sample preparation involved protein precipitation with acetonitrile following addition ofCN-deuterated SRA737 as internal standard.

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Jun
2017

Reference genome assemblies are valuable, as they provide insights into gene content, genetic evolution and domestication. The higher the quality of a reference genome assembly the more accurate the downstream analysis will be. During the last few years, major efforts have been made towards improving the quality of genome assemblies.

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Dec
1969

One may measure the kinetic rate constants associated with biochemical reactions using an optical biosensor: an instrument in which ligand molecules are convected through a flow cell over a surface to which receptors are immobilized. If there are multiple reactants, one is faced with the problem of fitting multiple kinetic rate constants to one signal, since data from all of the reacting species is lumped together. Even in the presence of ambiguous data, one may use a series of experiments to accurately determine the rate constants.

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