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Exposure to early life adversity (ELA) has been identified as a major risk factor in the development of major depressive disorder (MDD). It is hypothesized that a mediating mechanism may be environmentally induced alterations in gene function. In our REDEEM (Research in depression: endocrinology, epigenetics and neuroimaging) project we are examining possible epigenetic difference in some previously investigated target genes relevant to depression. To this end, methylation of the following genes were measured: NR3C1 (HPA axis), SLC6A4 (serotonin neurotransmitter function), and CD3ɛ (T cell receptor gene). We also looked at possible trans-generational transmission of epigenetic markers in a mother-baby sample.
DNA was isolated from depressed patients and controls and babies and a portion of the above genes, encompassing our regions of interest, were amplified by PCR. Percentage methylation levels were measured by pyrosequencing. mRNA was also measured for some gene products to see if function was related to methylation. HPA axis function was measured with serial saliva samples throughout the day.
to date: Methylation was increased in the CD3ɛ promoter in depressed subjects relative to controls. In the total group, those exposed to ELA had significantly increased methylation at this site. Levels of CD3ɛ mRNA levels were inversely related to methylation. There were some relationships between maternal ELA and baby methylation at the sites examined.
Consistent with an allostatic model of ELA damage, our findings suggest an alteration in epigenetic function in acquired immunity and the HPA axis, mediated by ELA. Findings will be discussed.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
The aim of this research was to look at the emergence of wearable technology and the internet of things (IoT) and their current and potential use in the health and care area. There is a wide and ever-expanding range of wearables, devices, apps, data aggregators and platforms allowing the measurement, tracking and aggregation of a multitude of health and lifestyle measures, information and behaviours. The use and application of such technology and the corresponding richness of data that it can provide bring the health and care insurance market both potential opportunities and challenges. Insurers across a range of fields are already engaging with this type of technology in their proposition designs in areas such as customer engagement, marketing and underwriting. However, it seems like we are just at the start of the journey, on a learning curve to find the optimal practical applications of such technology with many aspects as yet untried, tested or indeed backed up with quantifiable evidence. It is clear though that technology is only part of the solution, on its own it will not engage or change behaviours and insurers will need to consider this in terms of implementation and goals. In the first weeks of forming this working party, it became evident that the potential scope of this technology, the information already out there and the pace of development of it, is almost overwhelming. With many yet-unanswered questions the paper focuses on pulling together in one place relevant information for the consideration of the health and care actuary, and also to open the reader’s eyes to potential future innovations by drawing on use of the technology in other markets and spheres, and the “science fiction–like” new technology that is just around the corner. The paper explores:
an overview of wearables and IoT and available measures,
examples of how this technology is currently being used,
risks and challenges,
future technology developments and
what this may mean for the future of insurance.
Insurers who engage now are likely to be on an evolving business case model and product development journey, over which they can build up their understanding and interpretation of the data that this technology can provide. An exciting area full of potential – when and how will you get involved?
This paper reviews recent research into predicting the eating qualities of beef. A range of instrumental and grading approaches have been discussed, highlighting implications for the European beef industry. Studies incorporating a number of instrumental and spectroscopic techniques illustrate the potential for online systems to non-destructively measure muscle pH, colour, fat and moisture content of beef with R2 (coefficient of determination) values >0.90. Direct predictions of eating quality (tenderness, flavour, juiciness) and fatty acid content using these methods are also discussed though success is greatly variable. R2 values for instrumental measures of tenderness have been quoted as high as 0.85 though R2 values for sensory tenderness values can be as low as 0.01. Discriminant analysis models can improve prediction of variables such as pH and shear force, correctly classifying beef samples into categorical groups with >90% accuracy. Prediction of beef flavour continues to challenge researchers and the industry alike, with R2 values rarely quoted above 0.50, regardless of instrumental or statistical analysis used. Beef grading systems such as EUROP and United States Department of Agriculture systems provide carcase classification and some indication of yield. Other systems attempt to classify the whole carcase according to expected eating quality. These are being supplemented by schemes such as Meat Standards Australia (MSA), based on consumer satisfaction for individual cuts. In Australia, MSA has grown steadily since its inception generating a 10% premium for the beef industry in 2015-16 of $187 million. There is evidence that European consumers would respond to an eating quality guarantee provided it is simple and independently controlled. A European beef quality assurance system might encompass environmental and nutritional measures as well as eating quality and would need to be profitable, simple, effective and sufficiently flexible to allow companies to develop their own brands.
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.
The geodesic flow on the unit tangent bundle of a closed surface of constant negative curvature is one of the earliest examples of an ergodic dynamical system. This was first proven by G. A. Hedlund in 1936. Soon afterwards, it was reproved by E. Hopf, who also generalized to the case of closed surfaces of variable negative curvature. Hopf's proof already indicated the relevance of negative curvature to the ergodicity of the geodesic flow. About 20 years later, Hopf's theorem was generalized by Anosov to geodesic flows on unit tangent bundles of higher dimensional closed negatively curved manifolds.
Around the same time, combining certain basic results in geometry and topology, it was observed that the fundamental group of a closed manifold M of negative curvature determines M up to homotopy equivalence. Mostow's celebrated strong rigidity theorem (1968) showed that, within the class of closed locally symmetric spaces M of non-compact type of dimension ≥ 3, the fundamental group π1(M) determines M up to isometry (possibly after scaling the metric by a positive constant). Further study of this rigidity phenomenon led to two important generalizations. On the one hand, Margulis established his super-rigidity theorem in higher rank. Using the harmonic map techniques of Eells-Sampson, versions of the super-rigidity theorem were established for certain rank 1 cases by Corlette, Jost-Yau and Mok-Siu-Yeung. On the other hand, it led Ballmann-Brin-Eberlein to introduce, in the mid 1980's, the notion of geometric rank. Generalizing a notion that existed for locally symmetric spaces, this culminated in the rank rigidity theorem due, independently, to Ballmann and Burns-Spazier. Around this time, Gromov realized that many results of this nature could be formulated and proved, in a synthetic way, in the more general setting of metric spaces of non-positive curvature. The study of this broader class of spaces resulted in certain new rigidity phenomena (such as quasi-isometric rigidity). It also allowed these techniques to be applied to the study of certain infinite groups. Research in this direction has since exploded and created the whole new field of geometric group theory.
The ICM 2010 satellite conference 'Geometry, Topology and Dynamics in Negative Curvature' afforded an excellent opportunity to discuss various aspects of this fascinating interdisciplinary subject in which methods and techniques from geometry, topology, and dynamics often interact in novel and interesting ways. Containing ten survey articles written by some of the leading experts in the field, this proceedings volume provides an overview of important recent developments relating to negative curvature. Topics covered include homogeneous dynamics, harmonic manifolds, the Atiyah Conjecture, counting circles and arcs, and hyperbolic buildings. Each author pays particular attention to the expository aspects, making the book particularly useful for graduate students and mathematicians interested in transitioning from other areas via the common theme of negative curvature.
A community outbreak of legionellosis occurred in Barrow-in-Furness, Cumbria, during July and August 2002. A descriptive study and active case-finding were instigated and all known wet cooling systems and other potential sources were investigated. Genotypic and phenotypic analysis, and amplified fragment length polymorphism of clinical human and environmental isolates confirmed the air-conditioning unit of a council-owned arts and leisure centre to be the source of infection. Subsequent sequence-based typing confirmed this link. One hundred and seventy-nine cases, including seven deaths [case fatality rate (CFR) 3·9%] were attributed to the outbreak. Timely recognition and management of the incident very likely led to the low CFR compared to other outbreaks. The outbreak highlights the responsibility associated with managing an aerosol-producing system, with the potential to expose and infect a large proportion of the local population and the consequent legal ramifications and human cost.
The Australian Square Kilometre Array Pathfinder (ASKAP) will give us an unprecedented opportunity to investigate the transient sky at radio wavelengths. In this paper we present VAST, an ASKAP survey for Variables and Slow Transients. VAST will exploit the wide-field survey capabilities of ASKAP to enable the discovery and investigation of variable and transient phenomena from the local to the cosmological, including flare stars, intermittent pulsars, X-ray binaries, magnetars, extreme scattering events, interstellar scintillation, radio supernovae, and orphan afterglows of gamma-ray bursts. In addition, it will allow us to probe unexplored regions of parameter space where new classes of transient sources may be detected. In this paper we review the known radio transient and variable populations and the current results from blind radio surveys. We outline a comprehensive program based on a multi-tiered survey strategy to characterise the radio transient sky through detection and monitoring of transient and variable sources on the ASKAP imaging timescales of 5 s and greater. We also present an analysis of the expected source populations that we will be able to detect with VAST.
The objective of the present study was to utilise an accurate canine pedometer methodology and to assess the relationship between activity and body condition score (BCS) in dogs. Initial methodology validation used videography and pedometer step measurements to assess actual steps taken in comparison with pedometer readings for twenty large, medium and small dogs. During the validation, dogs considered to be medium or large breed showed no significant difference between pedometer readings and actual steps taken. A total of seventy-seven obese and non-obese dogs over 35 cm (14 inches) shoulder height and over 10 kg were recruited from a dog obesity clinic and a community sample to assess daily walking activity. Body condition scoring and pedometer steps were assessed on three separate weeks during a 10-week period. During the activity monitoring, daily step counts ranged from 5555 to 39 970 steps/d among the seventy-seven medium and large dogs. Dogs’ BCS were inversely correlated with average daily steps (Spearman's ρ = − 0·442, P < 0·0001). The present study identified a significant inverse correlation between daily walking steps and BCS over a range from 4 to 9 out of 9 (P < 0·0001).
Regional differences in the response of mice to infection with three strains of dermotropic Leishmania spp. were shown for skin covering the trunk. Lesions tended to appear earlier and to grow more rapidly on sites over the caudal half of the body than the cranial half, and caudal lesions were more likely than cranial ones to result in metastatic disease in susceptible strains of mice. Site-related variations in lesion development were observed in different strains of mice as well as in golden hamsters. The effect of these regional differences on the development of some parasite-specific, immunological reactions was examined, as were parasite thermosensitivity and location-related variations in host skin temperature as possible explanations.
It is unclear whether Axis II psychopathology or co-morbid clinical syndromes result in the treatment-seeking behaviour and social impairment of patients with borderline personality disorder (BPD). This study examined the independent associations between social functioning and service use and Axis I and Axis II disorders in persons with BPD in the national household population of Britain.
The study was a cross-sectional survey of adults aged 16–74 years in households (n=8397). Data included self-reported consultations with health-care professionals and behavioural problems. Diagnosis was determined by computer-assisted interviews. Analyses included logistic regression adjusting for demography, co-morbid Axis I clinical syndromes and other Axis II disorders.
Consultation in the past year was reported by 57.5% of persons with BPD but only 13.4% reported lifetime psychiatric admission. BPD was not independently associated with impaired functioning but was associated with co-morbid psychotic, depressive and anxiety disorders. Only general practitioners (GPs) were consulted for problems independently due to BPD.
Functional effects of BPD are mediated through co-morbid clinical syndromes, not Axis II psychopathology. A subgroup do not have co-morbid disorders or seek treatment, and are high functioning.