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Flaviviruses include many viruses causing encephalitis, including West Nile encephalitis, St. Louis encephalitis, tick-borne encephalitis and Japanese encephalitis. Human pegivirus genotype-1 (HPgV-1) is a lesser known member of the Flaviviridae family and has been identified in human serum, cerebrospinal fluid and brain tissue. Here, we describe two adult patients with fatal HPgV-1-associated encephalitis. Neuroimaging revealed multifocal lesions, initially present in the periventricular and brain stem white matter, then one year later throughout the corona radiata bilaterally with marked involvement of the brainstem and cervical spinal cord. Phylogenetic analyses of HPgV-1 showed clustering of brain-derived sequences from both patients with other human pegiviruses. In both patients, a novel 87-nucleotide deletion in the viral NS2 gene was detected. The presence of positive and negative strand HPgV-1 RNA and viral antigens in both patients indicated viral persistence and replication in the CNS. Autopsy showed lymphocyte infiltration and gliosis predominantly in white matter of the brain and brain stem but, to a lesser extent, also in grey matter. Immunofluorescence revealed HPgV-1 NS5A antigen in lymphocytes as well as in astrocytes and oligodendrocytes. Thus, we hypothesize that the novel deletion in the NS2 coding region may have caused HPgV-1 neuroadaptation or might represent a yet unrecognized genotype of human pegivirus.
This presentation will enable the learner to:
1.Describe the clinical and neuropathological features of fatal human pegivirus-associated encephalitis
2.Recognize the importance of molecular analysis in encephalitis cases with unknown etiology
The Garamantes were the earliest urbanised population in the Central Sahara, and their socio-political and economic histories have been the subject of extensive study.However, little is known about their biological origins. Building on the results obtained in the Desert Migrations Project, the biocultural theme within the Trans-SAHARA Project has sought to answer two main questions relating to human migration in the Central Sahara. First, it aimed to determine what (if any) biological and cultural links can be established between the historical kingdom of the Garamantes and the preceding late Neolithic (Pastoral) and contemporary peoples in the surrounding Saharan, Sahelian, Nilotic and Mediterranean regions. Second, the project aimed to investigate aspects of the diet and individual mobility of the people who were buried in the Garamantian cemeteries of the Wadi al-Ajal, in direct comparison with results from the analysis of people from the surrounding regions.
To date, there are no recent studies identifying the prevalence of parasites of human and veterinary importance in dogs and cats in Ireland. The interaction between pets and wildlife species in the environment is an important source of parasite exposure to canids and felines, and one likely to be heightened in the stray animal population. This study aimed to establish the prevalence of endoparasites in unowned dogs and cats in County Dublin, Ireland. Feces from stray dogs (n = 627) and cats (n = 289) entering a rehoming centre were collected immediately after defecation. The main parasitic agents detected were ascarids (15.52 and 30.26%), Cystoisospora (3.27 and 3.69%), Giardia spp. (6.02 and 1.84%) and lungworms (0.64 and 2.08%), in dogs and cats respectively. Animals younger than 3 months of age were more likely to be infected with ascarids (P < 0.001) and Cystoisospora spp. (P = 0.008 and P = 0.014) than older animals. All lungworms were morphologically identified and dogs were infected with Angiostrongylus vasorum (0.48%) and Crenosoma vulpis (0.16%) whereas cats were only infected with Aelurostrongylus abstrusus (2.08%). This represents the first prevalence study of stray animals in Ireland. Data collected will inform the treatment and in addition, the future monitoring and control studies of parasite populations.
To describe the behavioural and psychiatric problems found in nursing home psychiatric referrals in the Dublin South city area.
We undertook two consecutive surveys of nursing home referrals to the St James’s Hospital psychiatry of old age service over a 2-year period. During the second survey a new clinical nurse specialist was specifically appointed to manage the seven nursing homes included in the study.
The most common reason for referral during survey one was uncooperative/aggressive behaviour (22%). For survey two, patients were most commonly referred for low mood (31%) or agitation (29%). During survey one, the majority of patients assessed were diagnosed with behavioural and psychological symptoms of dementia (41%). This was also a prevalent diagnosis during survey two, affecting 27% of those referred. Only 7% of patients were considered to be delirious during survey one. This rose to 31% the following year making it the most common diagnosis during survey two. Over the 2-year study period, 7% of referred patients were diagnosed with depression. In terms of prescribing practices, the discontinuation rate of antipsychotic mediation following psychiatric input was 13% in survey one. By survey two, this had risen to 47%.
Delirium is often undetected and untreated in nursing homes. Residents presenting with psychiatric symptoms should undergo routine bloods and urinalysis prior to psychiatric referral. Dedicated input from trained psychiatric nursing staff can lead to both an improvement in the recognition of delirium and reduced prescribing rates of antipsychotic medication.
Childhood adversity predicts adolescent suicidal ideation but there are few studies examining whether the risk of childhood adversity extends to suicidal ideation in midlife. We hypothesized that childhood adversity predicts midlife suicidal ideation and this is partially mediated by adolescent internalizing disorders, externalizing disorders and adult exposure to life events and interpersonal difficulties.
At 45 years, 9377 women and men from the UK 1958 British Birth Cohort Study participated in a clinical survey. Childhood adversity was prospectively assessed at the ages of 7, 11 and 16 years. Suicidal ideation at midlife was assessed by the depressive ideas subscale of the Revised Clinical Interview Schedule. Internalizing and externalizing disorders were measured by the Rutter scales at 16 years. Life events, periods of unemployment, partnership separations and alcohol dependence were measured through adulthood.
Illness in the household, paternal absence, institutional care, parental divorce and retrospective reports of parental physical and sexual abuse predicted suicidal ideation at 45 years. Three or more childhood adversities were associated with suicidal ideation at 45 years [odds ratio (OR) 4.31, 95% confidence interval (CI) 2.67–6.94]. Psychological distress at 16 years partially mediated the associations of physical abuse (OR 3.41, 95% CI 2.29–5.75), sexual abuse (OR 4.99, 95% CI 2.90–11.16) with suicidal ideation. Adult life events partially mediated the association of parental divorce (OR 6.34, 95% CI −7.16 to 36.75) and physical (OR 9.59, 95% CI 4.97–27.88) and sexual abuse (OR 6.59, 95% CI 2.40–38.36) with suicidal ideation at 45 years.
Adversity in childhood predicts suicidal ideation in midlife, partially mediated by adolescent internalizing and externalizing disorders, adult life events and interpersonal difficulties. Understanding the pathways from adversity to suicidal ideation can inform suicide prevention and the targeting of preventive interventions.
Deep observations of galaxy outskirts reveal faint extended stellar components (ESCs) of streams, shells, and halos, which are ghostly remnants of the tidal disruption of satellite galaxies. We use cosmological galaxy formation simulations in Cold Dark Matter (CDM) and Warm Dark Matter (WDM) models to explore how the dark matter model influences the spatial, kinematic, and orbital properties of ESCs. These reveal that the spherically averaged stellar mass density at large galacto-centric radius can be depressed by up to a factor of ~10 in WDM models relative to the CDM model, reflecting the anticipated suppressed abundance of satellite galaxies in WDM models. However, these differences are much smaller in WDM models that are compatible with observational limits, and are comparable in size to the system-to-system variation we find within the CDM model. This suggests that it will be challenging to place limits on dark matter using only the unresolved ESC.
Major depressive disorder (MDD) is a common and disabling condition with well-established heritability and environmental risk factors. Gene–environment interaction studies in MDD have typically investigated candidate genes, though the disorder is known to be highly polygenic. This study aims to test for interaction between polygenic risk and stressful life events (SLEs) or childhood trauma (CT) in the aetiology of MDD.
The RADIANT UK sample consists of 1605 MDD cases and 1064 controls with SLE data, and a subset of 240 cases and 272 controls with CT data. Polygenic risk scores (PRS) were constructed using results from a mega-analysis on MDD by the Psychiatric Genomics Consortium. PRS and environmental factors were tested for association with case/control status and for interaction between them.
PRS significantly predicted depression, explaining 1.1% of variance in phenotype (p = 1.9 × 10−6). SLEs and CT were also associated with MDD status (p = 2.19 × 10−4 and p = 5.12 × 10−20, respectively). No interactions were found between PRS and SLEs. Significant PRSxCT interactions were found (p = 0.002), but showed an inverse association with MDD status, as cases who experienced more severe CT tended to have a lower PRS than other cases or controls. This relationship between PRS and CT was not observed in independent replication samples.
CT is a strong risk factor for MDD but may have greater effect in individuals with lower genetic liability for the disorder. Including environmental risk along with genetics is important in studying the aetiology of MDD and PRS provide a useful approach to investigating gene–environment interactions in complex traits.
The dynamics of one-dimensional, piston-driven hydrogen–air detonations are predicted in the presence of physical mass, momentum and energy diffusion. The calculations are automatically verified by the use of an adaptive wavelet-based computational method which correlates a user-specified error tolerance to the error in the calculations. The predicted frequency of 0.97 MHz for an overdriven pulsating detonation agrees well with the 1.04 MHz frequency observed by Lehr in a shock-induced combustion experiment around a spherical projectile, thus giving a limited validation for the model. A study is performed in which the supporting piston velocity is varied, and the long time behaviour is examined for an initially stoichiometric mixture at 293.15 K and 1 atm. Several distinct propagation behaviours are predicted: a stable detonation, a high-frequency pulsating detonation, a pulsating detonation with two competing modes, a low-frequency pulsating detonation and a propagating detonation with many active frequencies. In the low-frequency pulsating mode, the long time behaviour undergoes a phenomenon similar to period-doubling. Harmonic analysis is used to examine how the frequency of the pulsations evolves as the supporting piston velocity is varied. It is found that the addition of viscosity shifts the neutral stability boundary by about 2 % with respect to the supporting piston velocity. As the supporting piston velocity is lowered, the intrinsic instability grows in strength, and the effect of viscosity is weakened such that the results are indistinguishable from the inviscid predictions.
Increasing rates of young people not in education, employment or training (NEETs) are a cause of concern both in Ireland and internationally, but little longitudinal research has examined the link between psychiatric disorder in young people and NEET status.
The Challenging Times (CT) Study is a longitudinal, population-based study of psychopathology among 212 young Irish people. Clinical interviews were performed at two time points: 12–15 years and 19–24 years.
NEET status in young adulthood was associated with a sevenfold increased risk of current suicidal ideation. This result was independent of prior adolescent mental disorder. NEET young people had a fourfold increased odds of being diagnosed with a mental disorder in childhood or early adolescence compared with their economically active peers. NEET young people were at an almost threefold increased risk of any mental health disorder a twofold increased risk of anxiety disorder and threefold increased odds of suicide attempts over their lifetime compared with economically active peers.
NEET young people are at increased risk for mental disorder and suicidal ideation. The association is bidirectional, as prior mental disorder in adolescence appeared to account for much of the association between NEET status and current mental health problems. However, economic inactivity conveys an increased risk for suicidal ideation over and above that due to prior disorder. Our findings provide a compelling economic and societal argument for early intervention and treatment of mental disorder and the importance of vocational interventions for reducing suicide risk in young adults.
Strategies to dissect phenotypic and genetic heterogeneity of major depressive disorder (MDD) have mainly relied on subphenotypes, such as age at onset (AAO) and recurrence/episodicity. Yet, evidence on whether these subphenotypes are familial or heritable is scarce. The aims of this study are to investigate the familiality of AAO and episode frequency in MDD and to assess the proportion of their variance explained by common single nucleotide polymorphisms (SNP heritability).
For investigating familiality, we used 691 families with 2–5 full siblings with recurrent MDD from the DeNt study. We fitted (square root) AAO and episode count in a linear and a negative binomial mixed model, respectively, with family as random effect and adjusting for sex, age and center. The strength of familiality was assessed with intraclass correlation coefficients (ICC). For estimating SNP heritabilities, we used 3468 unrelated MDD cases from the RADIANT and GSK Munich studies. After similarly adjusting for covariates, derived residuals were used with the GREML method in GCTA (genome-wide complex trait analysis) software.
Significant familial clustering was found for both AAO (ICC = 0.28) and episodicity (ICC = 0.07). We calculated from respective ICC estimates the maximal additive heritability of AAO (0.56) and episodicity (0.15). SNP heritability of AAO was 0.17 (p = 0.04); analysis was underpowered for calculating SNP heritability of episodicity.
AAO and episodicity aggregate in families to a moderate and small degree, respectively. AAO is under stronger additive genetic control than episodicity. Larger samples are needed to calculate the SNP heritability of episodicity. The described statistical framework could be useful in future analyses.
Breastfeeding has been an important survival trait during human history, though it has long been recognized that individuals differ in their exact breastfeeding behavior. Here our aims were, first, to explore to what extent genetic and environmental influences contributed to the individual differences in breastfeeding behavior; second, to detect possible genetic variants related to breastfeeding; and lastly, to test if the genetic variants associated with breastfeeding have been previously found to be related with breast size. Data were collected from a large community-based cohort of Australian twins, with 3,364 women participating in the twin modelling analyses and 1,521 of them included in the genome-wide association study (GWAS). Monozygotic (MZ) twin correlations (rMZ = 0.52, 95% CI 0.46–0.57) were larger than dizygotic (DZ) twin correlations (rDZ = 0.35, 95% CI 0.25–0.43) and the best-fitting model was the one composed by additive genetics and unique environmental factors, explaining 53% and 47% of the variance in breastfeeding behavior, respectively. No breastfeeding-related genetic variants reached genome-wide significance. The polygenic risk score analyses showed no significant results, suggesting breast size does not influence breastfeeding. This study confers a replication of a previous one exploring the sources of variance of breastfeeding and, to our knowledge, is the first one to conduct a GWAS on breastfeeding and look at the overlap with variants for breast size.
The coming decade will witness a deluge of data from next generation galaxy surveys such as the Square Kilometre Array and Euclid. How can we optimally and robustly analyse these data to maximise scientific returns from these surveys? Here we discuss recent work in developing both the conceptual and software frameworks for carrying out such analyses and their application to the dark matter halo mass function. We summarise what we have learned about the HMF from the last 10 years of precision CMB data using the open-source HMFcalc framework, before discussing how this framework is being extended to the full Halo Model.
An unhealthy body mass index (BMI) has been associated with depression but the direction of association is uncertain. Our aim was to estimate the co-morbidity and direction of association between BMI and depressive symptoms at several ages, from childhood to mid-adulthood.
The data were from 18 558 individuals born in 1 week in March 1958, in England, Scotland and Wales, with follow-up at ages 7, 11, 16, 23, 33, 42, 45 and 50 years. Depression (scores ⩾90th percentile) was identified from child/adolescent (teacher questionnaires) and adult (self-complete questionnaires and clinical interview) measures. BMI (kg/m2) measured in child/adolescence and adulthood was classified as underweight, normal, overweight or obese.
In cross-sectional analyses, obesity and underweight (not overweight) from 11 to 45 years were associated respectively with 1.3–2.1 and 1.5–2.3 times the risk of depression compared with normal weight. Using the time-lagged generalized estimating equation (GEE) approach, we tested (a) whether underweight or obesity at prior ages (7 to 45 years) predicted subsequent risk of depression (11 to 50 years), adjusting for baseline depression; and (b) whether depression at prior ages (7 to 42 years) predicted subsequent risk of underweight or obesity (11 to 45 years), adjusting for baseline BMI. In longitudinal analyses, underweight predicted subsequent depression in both sexes [odds ratio (OR) 1.25, 95% confidence interval (CI) 1.11–1.40] and depression predicted subsequent underweight in males only (OR 1.84, 95% CI 1.52–2.23). Obesity predicted subsequent depressive symptoms in females only (OR 1.34, 95% CI 1.14–1.56), but depression did not predict obesity.
Clinicians should consider screening routinely for depression patients with unhealthy BMI, namely underweight and obesity, and vice versa.
The characteristic prediction of the Cold Dark Matter (CDM) model of cosmological structure formation is that the Universe should contain a wealth of small-scale structure—low-mass dark matter haloes and subhaloes. However, galaxy formation is inefficient in their shallow potential wells and so we expect these low-mass haloes and subhaloes to be dark. Can we tell the difference between a Universe in which these low-mass haloes are present but dark and one in which they never formed, thereby providing a robust test of the CDM model? We address this question using cosmological N-body simulations to examine how properties of low-mass haloes that are potentially accessible to observation, such as their spatial clustering, rate of accretions and mergers onto massive galaxies, and the angular momentum content of massive galaxies, differ between a fiducial ΛCDM model and dark matter models in which low-mass halo formation is suppressed. Adopting an effective cut-off mass scale Mcut below which small-scale power is suppressed in the initial conditions, we study dark matter models in which Mcut varies between 5×109h−1M⊙ and 1011h−1M⊙, equivalent to the host haloes of dwarf and low-mass galaxies. Our results show that both the clustering strength of low-mass haloes around galaxy-mass primaries and the rate at which they merge with these primaries are sensitive to the assumed value of Mcut; in contrast, suppressing low-mass halo formation has little influence on the angular momentum content of galaxy-mass haloes—it is the quiescence or violence of a halo's assembly history that has a more marked effect. However, we expect that measuring the effect on spatial clustering or the merger rate is likely to be observationally difficult for realistic values of Mcut, and so isolating the effect of this small-scale structure would appear to be remarkably difficult to detect, at least in the present day Universe.
Heritage, memory, community archaeology and the politics of the past form the main strands running through the papers in this volume. The authors tackle these subjects from a range of different philosophical perspectives, with many drawing on the experience of recent community, commercial and other projects. Throughout, there is a strong emphasis on both the philosophy of engagement and with its enactment in specific contexts; the essays deal with an interest in the meaning, value and contested nature of the recent past and in the theory and practice of archaeological engagements with that past.
Chris Dalglish is a lecturer in archaeology at the University of Glasgow. Contributors: Julia Beaumont, David Bowsher, Terry Brown, Jo Buckberry, Chris Dalglish, James Dixon, Audrey Horning, Robert Isherwood, Robert C Janaway, Melanie Johnson, Siân Jones, Catriona Mackie, Janet Montgomery, Harold Mytum, Michael Nevell, Natasha Powers, Biddy Simpson, Matt Town, Andrew Wilson
Community archaeology is a rapidly expanding approach to archaeological research. Whilst the archaeology itself is central to individual projects, issues of community' may be heavily implicated within the agendas of many project partners. In this paper, I will argue that community archaeology projects are complex arenas in which a variety of agendas are interwoven within both the planned activities and the unplanned outcomes that occur during the life of a project. Drawing on ethnographic evidence of community archaeology from my recently completed doctoral research as well as from recent experience of the proactive delivery of community archaeology I will focus on the role of memory in relation to both the initial design of community archaeology projects and also the ways in which projects come to be understood and valued by those who have supported and/or participated in them. I will identify projects as being arenas in which aspects of social memory can be central to much that is both planned for and experienced by participants. The rediscovery of lost memories, the preserving of fragile memories and the making of new memories will be shown to be especially significant within the narratives aggregating around individual community projects. I identify ‘living memory'sites as being especially meaningful and effective for community archaeology and argue that the event of a community archaeology project can serve as an arena for the construction of community in the present.