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There are a variety of causes of acute heart failure in children including myocarditis, genetic/metabolic conditions, and congenital heart defects. In cases with a structurally normal heart and a negative personal and family history, myocarditis is often presumed to be the cause, but we hypothesise that genetic disorders contribute to a significant portion of these cases. We reviewed our cases of children who presented with acute heart failure and underwent genetic testing from 2008 to 2017. Eighty-seven percent of these individuals were found to have either a genetic syndrome or pathogenic or likely pathogenic variant in a cardiac-related gene. None of these individuals had a personal or family history of cardiomyopathy that was suggestive of a genetic aetiology prior to presentation. All of these individuals either passed away or were listed for cardiac transplantation indicating genetic testing may provide important information regarding prognosis in addition to providing information critical to assessment of family members.
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.
The Mediterranean diet offers a range of health benefits. However, previous studies indicate that the restricted consumption of red meat in the diet may affect long-term sustainability in non-Mediterranean countries. A 24-week randomised controlled parallel cross-over design compared a Mediterranean diet supplemented with 2–3 serves per week of fresh, lean pork (MedPork) with a low-fat control diet (LF). Thirty-three participants at risk of CVD followed each intervention for 8 weeks, with an 8-week washout period separating interventions. The primary outcome was home-measured systolic blood pressure. Secondary outcomes included diastolic blood pressure, fasting lipids, glucose, insulin, C-reactive protein (CRP), body composition and dietary adherence. During the MedPork intervention, participants achieved high adherence to dietary guidelines. Compared with the MedPork intervention, the LF intervention led to greater reductions in weight (Δ = 0·65; 95 % CI: 0·04, 1·25 kg, P = 0·04), BMI (Δ = 0·25; 95 % CI: 0·03, 0·47 kg/m2, P = 0·01) and waist circumference (Δ = 1·40; 95 % CI: 0·45, 2·34 cm, P < 0·01). No significant differences were observed for blood pressure, lipids, glucose, insulin or CRP. These findings indicate that Australians are capable of adhering to a Mediterranean diet with 2–3 weekly serves of fresh, lean pork, which may offer a healthy alternative to LF diets in Australians at risk of CVD. Larger intervention studies are now required to demonstrate clinical efficacy of the diet in populations with elevated blood pressure.
We illustrate the extraordinary potential of the (far-IR) Origins Survey Spectrometer (OSS) on board the Origins Space Telescope (OST) to address a variety of open issues on the co-evolution of galaxies and AGNs. We present predictions for blind surveys, each of 1000 h, with different mapped areas (a shallow survey covering an area of 10 deg2 and a deep survey of 1 deg2) and two different concepts of the OST/OSS: with a 5.9 m telescope (Concept 2, our reference configuration) and with a 9.1 m telescope (Concept 1, previous configuration). In 1 000 h, surveys with the reference concept will detect from ∼1.9×106 to ∼8.7×106 lines from ∼4.8×105 to 2.7×106 star-forming galaxies and from ∼1.4×104 to ∼3.8×104 lines from ∼1.3×104 to 3.5×104 AGNs. The shallow survey will detect substantially more sources than the deep one; the advantage of the latter in pushing detections to lower luminosities/higher redshifts turns out to be quite limited. The OST/OSS will reach, in the same observing time, line fluxes more than one order of magnitude fainter than the SPICA/SMI and will cover a much broader redshift range. In particular it will detect tens of thousands of galaxies at z ≥ 5, beyond the reach of that instrument. The polycyclic aromatic hydrocarbons lines are potentially bright enough to allow the detection of hundreds of thousands of star-forming galaxies up to z ∼ 8.5, i.e. all the way through the reionisation epoch. The proposed surveys will allow us to explore the galaxy–AGN co-evolution up to z ∼ 5.5−6 with very good statistics. OST Concept 1 does not offer significant advantages for the scientific goals presented here.
The book brings together papers covering the most recent scientific research from the top endophyte researchers in the world. It presents the state of the art in our knowledge and technical capacity and explores future directions of this work. It is highly relevant and timely because of the need to improve global food security and its sustainability, and also to provide novel bioactive molecules for medicine. There is also a need to protect forestry in a changing and growing world. Endophytes offer a huge potential to reduce environmentally damaging agricultural inputs such as fertilisers and pesticides. They are also a largely overlooked group of organisms where much basic science remains to be undertaken. For example, new molecular tools of DNA profiling using high throughput environmental sequencing are allowing the exploration of a previously largely unknown resource. There is a pressing need to convert scientific research on endophytes into practical application. This book describes how that will be achieved.
In some environments, the survival and production of ryegrass and fescue is heavily reliant on its mutualistic association with Epichloë endophytes. Epichloë endophytes produce a range of bioactive alkaloids, or secondary metabolites that can be effective in deterring insect pests, although some have also been shown to be toxic to grazing animals. These endophytes are being used in grassland farming systems in Australia, New Zealand, USA and some parts of South America. However, to achieve this outcome there has been considerable investment into developing a research pipeline for delivery of animal-safe endophyte strains that are still capable of deterring insect pests and providing protection against abiotic stresses. The pipeline starts with the discovery and isolation of endophytes from wild populations of ryegrass and fescue, characterisation of the known alkaloids they produce, use of genetic markers to determine the relationship between known well-characterised strains and new strains entering the collection, determination of their bioactivity against insect pests of economic significance, understanding issues of compatibility of a strain of interest with the elite germplasm into which it has been inoculated, determining ease of transmission to subsequent seed generations, and ensuring there will be no or minimal animal health and welfare issues associated with using the strain in grazing systems.
A study to detect the diversity of endophytic Actinobacteria from Australian rice was conducted using culture-dependent and culture-independent methods. Rice samples were collected from the rice growing area near Yanco, New South Wales, Australia. Isolation of the endophytic Actinobacteria was done over two consecutive growing seasons. The results demonstrated that most isolates were obtained from plants 10 weeks and older, and only a few were found in younger plants. Microbispora spp. were the most commonly isolated endophytic Actinobacteria (94%) with Streptomyces spp. and other genera present at lower numbers (6%). The culture-dependent method findings were confirmed by T-RFLP profile analysis. Restriction digests using HhaI and RsaI also showed an abundance of terminal restriction fragments (TRFs) profiles related to the genus Microbispora. Furthermore, other biological properties of the endophytic Actinobacteria isolates were also determined. Four isolates, Saccharothrix OSH21, Saccharopolyspora OSR26, Streptomyces OSR46 and Microbispora OSR61, were found to suppress the growth of the pathogenic fungus Rhizoctonia solani. Moreover, these isolates might be able to promote plant growth by producing indole acetic acid or to solubilise phosphate making this nutrient available for plant uptake.
The fortuitous discovery of penicillin from Penicillium chrysogenum heralded the golden era of antibiotics. Since then, fungi have significantly contributed to the welfare of humans by producing bioactive compounds which have been used as antibacterial, anticancer, antioxidant and immunomodulatory agents. However, in recent years, microorganisms associated with plants have emerged as fountainheads of bioactive molecules with high therapeutic potential. In general terms, endophytes are an extremely diverse and ubiquitous group of microorganisms that resides within the living internal tissues of a host plant in a non-invasive manner. Endophytes communicate with their host plant through metabolic interactions which enables them to produce signal molecules with interesting biological activities. Further, the genetic recombination of endophytes with the host plant enables them to mimic the biological properties of the host and produce analogous bioactive compounds. Thus, they start producing the host plant phytochemicals when cultured independently. The endless need for potent drugs has prompted researchers to explore alternative avenues for finding novel bioactive molecules, and endophytes appear to be a plausible target for drug discovery. This chapter reviews the current research trends with these promising organisms.
There are increasing efforts aiming to utilise endophytes as biological control agents (BCAs) to improve crop production. However, reliability remains a major practical constraint for the development of novel BCAs. Many organisms are adapted to their specific habitat; it is optimistic to expect that a new organism added can find a niche or even out-compete those adapted and already present. Our approach for isolating novel BCAs for specific plant diseases is therefore to look in healthy plants in a habitat where disease is a problem, since we predict that it is more likely to find competitive strains among those present and adapted. In vitro inhibitory activities often do not correlate with in planta efficacy, especially since endophytes rely on intimate plant contact. They can, however, be useful to indicate modes of action. We therefore screen for in planta biological activity as early as possible in the process in order to minimise the risk of discarding valuable strains. Finally, some fungi are endophytic in one situation and pathogenic in another (the mutualism–parasitism continuum). This depends on their biology, environmental conditions, the formulation of inoculum, the health, developmental stage and cultivar of the host plant, and the structure of the plant microbiome.
Endophytes are any microbes that can live within plants. We divide them into three major functional groups: endosyms (endosymbionts), endopaths (pathogens) and endosympaths (those that exist in both forms along a mutualism–parasitism continuum). Within these groups, endophytologists recognise harmful pathogenic microbes and a diverse range of beneficial/commensal microbes, including bacteria and archaea, such as diazotrophs, and fungi, such as the vertically transmitted clavicipitaceous endophytes, the generally horizontally transmitted class 2 fungal endophytes, mycorrhizal fungi and dark septate endophytes. This chapter introduces the science of endophyte biology and its application for a world population that is projected to grow to over 9 billion by 2050. It explores the potential of endophytes for improved agricultural and silvicultural sustainability including: yield improvement and nutrition; biocontrol of pests and diseases; and abiotic stress resistance in the context of climate change. It outlines how bioprospectors are using endophytes as sources of novel metabolites for the pharmaceutical and biochemical industries, and describes how endophytes can be used in vitro to elicit the increased production of known secondary metabolites from plants.
Herbicide resistance within key driver weeds, such as common waterhemp [Amaranthus tuberculatus (Moq.) Sauer var. rudis (Sauer) Costea and Tardif ], constrains available management options for crop production. Routine surveillance for herbicide resistance provides a mechanism to monitor the development and spread of resistant populations over time. Furthermore, the identification and quantification of resistance mechanisms at the population level can provide information that helps growers develop effective management plans. Populations of Amaranthus spp., including A. tuberculatus, redroot pigweed (Amaranthus retroflexus L.), and Palmer amaranth (Amaranthus palmeri S. Watson), were collected from 51 fields in Ohio during the 2016 growing season. Twenty-four A. tuberculatus populations were screened for resistance to the herbicides lactofen, atrazine, and glyphosate. Phenotypically resistant plants were further investigated to determine the frequency of known resistance mechanisms. Resistance to lactofen was infrequently observed throughout the populations, with 8 of 22 populations exhibiting resistant plants. Within those eight resistant populations, the ΔG210 resistance mechanism was observed in 17 of 30 phenotypically resistant plants, and the remainder lacked all known resistance mechanisms. Resistance to atrazine was observed in 12 of 15 populations; however, a target-site resistance mechanism was not observed in these populations. Resistance to glyphosate was observed in all populations. Gene amplification was the predominant glyphosate-resistance mechanism (147 of 322 plants) in the evaluated populations. The Pro-106-Ser mutation was identified in 24 plants, half of which also possessed gene amplification. In this study, molecular screening generally underestimated the phenotypically observed resistance. Continued mechanism discovery and marker development is required for improved detection of herbicide resistance through molecular assays.
To examine the impact of multiple psychiatric disorders over the lifetime on risk of mortality in the general population.
Data came from a random community-based sample of 1397 adults in Atlantic Canada, recruited in 1992. Major depression, dysthymia, panic disorder, generalised anxiety disorder and alcohol use disorders were assessed using the Diagnostic Interview Schedule (DIS). Vital status of participants through 2011 was determined using probabilistic linkages to the Canadian Mortality Database. Cox proportional hazard models with age at study entry as the time scale were used to investigate the relationship between DIS diagnoses and mortality, adjusted for participant education, smoking and obesity at baseline.
Results suggested that mood and anxiety disorders rarely presented in isolation – the majority of participants experienced multiple psychiatric disorders over the lifetime. Elevated risk of death was found among men with both major depression and dysthymia (HR 2.56; 95% CI 1.12–5.89), depression and alcohol use disorders (HR 2.45; 95% CI 1.18–5.10) and among men and women who experienced both panic disorder and alcohol use disorders (HR 3.80; 95% CI 1.19–12.16).
The experience of multiple mental disorders over the lifetime is extremely common, and associated with increased risk of mortality, most notably among men. Clinicians should be aware of the importance of considering contemporaneous symptoms of multiple psychiatric conditions.
We describe the motivation and design details of the ‘Phase II’ upgrade of the Murchison Widefield Array radio telescope. The expansion doubles to 256 the number of antenna tiles deployed in the array. The new antenna tiles enhance the capabilities of the Murchison Widefield Array in several key science areas. Seventy-two of the new tiles are deployed in a regular configuration near the existing array core. These new tiles enhance the surface brightness sensitivity of the array and will improve the ability of the Murchison Widefield Array to estimate the slope of the Epoch of Reionisation power spectrum by a factor of ∼3.5. The remaining 56 tiles are deployed on long baselines, doubling the maximum baseline of the array and improving the array u, v coverage. The improved imaging capabilities will provide an order of magnitude improvement in the noise floor of Murchison Widefield Array continuum images. The upgrade retains all of the features that have underpinned the Murchison Widefield Array’s success (large field of view, snapshot image quality, and pointing agility) and boosts the scientific potential with enhanced imaging capabilities and by enabling new calibration strategies.
Little is known about the prevalence of mental health outcomes in UK personnel at the end of the British involvement in the Iraq and Afghanistan conflicts.
We examined the prevalence of mental disorders and alcohol misuse, whether this differed between serving and ex-serving regular personnel and by deployment status.
This is the third phase of a military cohort study (2014–2016; n = 8093). The sample was based on participants from previous phases (2004–2006 and 2007–2009) and a new randomly selected sample of those who had joined the UK armed forces since 2009.
The prevalence was 6.2% for probable post-traumatic stress disorder, 21.9% for common mental disorders and 10.0% for alcohol misuse. Deployment to Iraq or Afghanistan and a combat role during deployment were associated with significantly worse mental health outcomes and alcohol misuse in ex-serving regular personnel but not in currently serving regular personnel.
The findings highlight an increasing prevalence of post-traumatic stress disorder and a lowering prevalence of alcohol misuse compared with our previous findings and stresses the importance of continued surveillance during service and beyond.
Declaration of interest:
All authors are based at King's College London which, for the purpose of this study and other military-related studies, receives funding from the UK Ministry of Defence (MoD). S.A.M.S., M.J., L.H., D.P., S.M. and R.J.R. salaries were totally or partially paid by the UK MoD. The UK MoD provides support to the Academic Department of Military Mental Health, and the salaries of N.J., N.G. and N.T.F. are covered totally or partly by this contribution. D.Mu. is employed by Combat Stress, a national UK charity that provides clinical mental health services to veterans. D.MacM. is the lead consultant for an NHS Veteran Mental Health Service. N.G. is the Royal College of Psychiatrists’ Lead for Military and Veterans’ Health, a trustee of Walking with the Wounded, and an independent director at the Forces in Mind Trust; however, he was not directed by these organisations in any way in relation to his contribution to this paper. N.J. is a full-time member of the armed forces seconded to King's College London. N.T.F. reports grants from the US Department of Defense and the UK MoD, is a trustee (unpaid) of The Warrior Programme and an independent advisor to the Independent Group Advising on the Release of Data (IGARD). S.W. is a trustee (unpaid) of Combat Stress and Honorary Civilian Consultant Advisor in Psychiatry for the British Army (unpaid). S.W. is affiliated to the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Emergency Preparedness and Response at King's College London in partnership with Public Health England, in collaboration with the University of East Anglia and Newcastle University. The views expressed are those of the author(s) and not necessarily those of the National Health Service, the NIHR, the Department of Health, Public Health England or the UK MoD.
Melt electrospinning is a facile fabrication technique that can be utilized in the creation of microfibers without the use of solvent and with good control over feature placement. The available thermal energy of the melt electrospinning technique is often only utilized in the formation of the polymer melt but can also be used to thermodynamically drive chemical reactions. In this study, hybrid perovskite microcrystallites are synthesized in the polymer melt and electrospun to form composite microfibers. Unique hybrid perovskite microstructures were studied, elucidating mechanisms of formation at work in the polymer melt.