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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
In Ireland, National Clinical Programmes are being established to improve and standardise patient care throughout the Health Service Executive. In line with internationally recognised guidelines on the treatment of first episode psychosis the Early Intervention in Psychosis (EIP) programme is being drafted with a view to implementation by mental health services across the country. We undertook a review of patients presenting with a first episode of psychosis to the Dublin Southwest Mental Health Service before the implementation of the EIP. This baseline information will be used to measure the efficacy of our EIP programme.
Patients who presented with a first episode psychosis were retrospectively identified through case note reviews and consultation with treating teams. We gathered demographic and clinical information from patients as well as data on treatment provision over a 2-year period from the time of first presentation. Data included age at first presentation, duration of untreated psychosis, diagnosis, referral source, antipsychotic prescribing rates and dosing, rates of provision of psychological interventions and standards of physical healthcare monitoring. Outcome measures with regards to rates of admission over a 2-year period following initial presentation were also recorded.
In total, 66 cases were identified. The majority were male, single, unemployed and living with their family or spouse. The mean age at first presentation was 31 years with a mean duration of untreated psychosis of 17 months. Just under one-third were diagnosed with schizophrenia. Approximately half of the patients had no contact with a health service before presentation. The majority of patients presented through the emergency department. Two-thirds of all patients had a hospital admission within 2 years of presentation and almost one quarter of patients had an involuntary admission. The majority of patients were prescribed antipsychotic doses within recommended British National Formulary guidelines. Most patients received individual support through their keyworker and family intervention was provided in the majority of cases. Only a small number received formal Cognitive-Behavioural Therapy. Physical healthcare monitoring was insufficiently recorded in the majority of patients.
There is a shortage of information on the profile and treatment of patients presenting with a first episode of psychosis in Ireland. This baseline information is important in evaluating the efficacy of any new programme for this patient group. Many aspects of good practice were identified within the service in particular with regards to the appropriate prescribing of antipsychotic medication and the rates of family intervention. Deficiencies remain however in the monitoring of physical health and the provision of formal psychological interventions to patients. With the implementation of an EIP programme it is hoped that service provision would improve nationwide and to internationally recognised standards.
This article focuses on two of Kate Bush's post-Aerial (2005) albums: Director's Cut (2011) and 50 Words for Snow (2011). In these albums Bush plays with the temporal qualities of recorded music to create the conditions for self-reflexive internal time consciousness to emerge within the listener. I argue that self-reflexive internal time consciousness is a process that enables a listener to gain some understanding that they are embroiled in an act of perception forged via active engagement with recorded music. Bush creates these conditions in two principle ways: In Director's Cut she disturbs the memory of previous recorded versions that are re-visited on the album so they can be mobilised as new, interpretative-perceptive acts. In 50 Words for Snow she uses duration as a structure to support the construction of extensive perception. Bush plays with time on these albums because her conceptual music relies upon the uninterrupted unfolding of consciousness as it becomes interlaced with her recordings, understood in the Husserlian sense of temporal objects. Implicit to her temporal strategies is a critique of contemporary listening conditions and how they undermine the very forging of the perceptual act.
The rocky intertidal communities of Ireland contain a mix of cold- and warm-adapted species, however the spatial distribution of these communities has not been investigated in a systematic way. Based on a benthic community dataset collected in 2003 at 63 sites, several statistical analyses were combined with the aims of (i) detecting groups of similar communities and their spatial arrangement, (ii) relating these groups to environmental factors and (iii) identifying the species that drive the different community groups. Sørensen's index suggested two marine community groups, one of the east and south-east (termed ‘east’) and the other in the west, south-west and north (termed ‘west’). A second partition based on combined wave exposure and sea surface chlorophyll comprised four groups, as did a further partition based on combined sea surface and air temperatures. The spatial arrangement of wave height plus chlorophyll conditions agreed reasonably well with the binary marine community partition, but the temperature partition did not. The ‘east’ community appeared to be associated with low wave height and chlorophyll conditions. The species that were most influential to the ‘east’ community were Balanus crenatus, Austrominius modestus and Fucus vesiculosus. The ‘west’ sites were associated with high wave height/low chlorophyll (with some variation in this due to local shelter) and the species Paracentrotus lividus, Chthamalus stellatus, Alaria esculenta and Himanthalia elongata. A longitudinal pattern rather than one associated with latitude was evident in this marine community and local drivers rather than temperature clines appeared most important for the dominant community patterns.
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.
The occurrence of pearls in the ‘true’ oysters, the Ostreioidea, is poorly documented despite being the most produced mollusc species in the world. Oysters of the Crassostrea genus were collected in two different sites in southern Portugal where both Crassostrea angulata and C. gigas are present, namely in: (1) the Ria Formosa lagoon where pearls were not observed (N = 446); and (2) the Guadiana estuary where pearls were found in 12 out of the 798 oysters analysed. The pearls were located mainly at the edge of the right mantle lobe in the inhalant chamber and their maximum length ranged from 0.9 to 5.5 mm. Almost all the pearls had a white-cream colouration with the exception of two pearls that had a black-brown colour. X-ray diffraction analysis of one pearl showed that it was entirely calcitic with no traces of either aragonite or vaterite. The pearls observed were therefore non-nacreous pearls. Scanning electron microscopy (SEM) revealed a diversity of microstructures including prismatic, foliae-like sheets and blocky textures, i.e. highly reminiscent of the host oyster shell microstructures. Parasites (e.g. parasitic copepods, Haplosporidium-like plasmodia) and signs of diseases (e.g. foot disease) were observed in some of the oysters analysed, but they were not associated with the occurrence of pearls. The present work is one of the few studies on the occurrence of natural pearls in ‘true’ oysters and to our knowledge the first description of their microstructure by SEM.
Effective transition from child and adolescent mental health services (CAMHS) to adult services is one of the main challenges currently facing child psychiatry today
The Young Adult 1Programme (YAP) based at St. Patrick’s University Hospital Dublin, is a group based day programme especially designed to meet the needs of younger people aged 18–25 and support them through this difficult period.
To examine the effectiveness of participation in YAP for young adults with mental illness. To determine whether participation in particular aspects of the programme prove more beneficial and what factors might be associated with outcome.
All patients enrolled in YAP between 1 September 2011 and 31 August 2012 were included in the study. Each patient was assessed using the Health of the Nation Outcome Scales (HONOS) and Global Assessment of Functioning (GAF) rating scale before beginning the programme and after discharge in order to evaluate improvement. The frequency of attendance at individual group sessions was recorded. Patient and illness variables were also recorded, for example demographics, diagnosis.
A total of 101 service users were in enrolled in YAP during this 12-month period. Eight service users could not be used for analysis, as they did not have a complete data set, mostly due to failure to attend for discharge HONOS/GAF ratings
Using a paired sample t-test, there is a significant reduction in HONOS: Mean df=1.3, s.d.=1.09 (95% CI=1.08–1.53), p<0.001
Using a paired sample t-test, there is a significant increase in GAF: Mean df=9.25, s.d.=7.69 (95% CI=7.66–10.83), p<0.001
Improvements in HONOS and GAF scores are significantly correlated with better attendance at the programme (p<0.04, <0.00 respectively).
More attendance at YAP sessions correlates with better improvement in both HONOS and GAF rating scores.
An awareness of the importance of nutritional status in hospital settings began more than 40 years ago. Much has been learned since and has altered care. For the past 40 years several large studies have shown that cancer patients are amongst the most malnourished of all patient groups. Recently, the use of gold-standard methods of body composition assessment, including computed tomography, has facilitated the understanding of the true prevalence of cancer cachexia (CC). CC remains a devastating syndrome affecting 50–80 % of cancer patients and it is responsible for the death of at least 20 %. The aetiology is multifactorial and complex; driven by pro-inflammatory cytokines and specific tumour-derived factors, which initiate an energy-intensive acute phase protein response and drive the loss of skeletal muscle even in the presence of adequate food intake and insulin. The most clinically relevant phenotypic feature of CC is muscle loss (sarcopenia), as this relates to asthenia, fatigue, impaired physical function, reduced tolerance to treatments, impaired quality of life and reduced survival. Sarcopenia is present in 20–70 % depending on the tumour type. There is mounting evidence that sarcopenia increases the risk of toxicity to many chemotherapy drugs. However, identification of patients with muscle loss has become increasingly difficult as 40–60 % of cancer patients are overweight or obese, even in the setting of metastatic disease. Further challenges exist in trying to reverse CC and sarcopenia. Future clinical trials investigating dose reductions in sarcopenic patients and dose-escalating studies based on pre-treatment body composition assessment have the potential to alter cancer treatment paradigms.
Background: A large proportion of people living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) suffer from neurocognitive impairment (NCI). The causes of the NCI are multifold in HIV infection although a subset of HIV/AIDS patients are affected by the spectrum syndrome, HIV-associated neurocognitive disorder (HAND). We investigated the Montreal Cognitive Assessment (MoCA) in relation to clinical, demographic and laboratory findings as well as its ability to predict symptomatic HAND (sHAND) among patients with HIV/AIDS. Methods: All subjects were receiving regular HIV care including CD4+ T cell counts, plasma viral load measurements, clinical evaluations and antiretroviral therapy. The diagnosis of sHAND was based upon clinical, neuroimaging, and neuropsychological assessments.Results: Among HIV-1 seropositive subjects (n=125), ethnicity, education and employment were positively correlated with their MoCA scores (p<0.05). In contrast, polypharmacy, central nervous system penetration-effectiveness (CPE) score, antiretroviral drug exposure, substance use and nucleoside/nucleotide reverse transcriptase inhibitor side effects were negatively correlated with MoCA scores (p<0.05). Of note, MoCA scores were not associated with CD4 T cell nadir levels, age, peak viral load, or veterans aging cohort study index. In subjects with or without sHAND, mean MoCA scores differed (sHAND, 22.8±3.51; non-HAND 25.2±2.64) (p<0.05) with a receiver operating characteristic curve showing an area under curve of 0.71 and an optimal MoCA cut-off value of 23.5 when compared to the established diagnostic paradigm. Conclusions: MoCA scores were generally lower in this HIV/AIDS population compared to reported scores in the general population. MoCA performance was associated with multiple clinical variables but displayed limited predictive utility in detecting sHAND.
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.
This chapter deals with approximation methods, mainly through the use of series. After a short discussion of approximation of known functions, we focus on approximately solving equations for unknown functions. One might wonder why anyone should bother with an approximate solution in favor of an exact solution. There are many justifications. Often physical systems are described by complicated equations with detailed exact solutions; the details of the solution may in fact obscure easy interpretation of results, rendering the solution to be of small aid in discerning trends or identifying the most important causal agents. A carefully crafted approximate solution will often yield a result that exposes the important driving physics and filters away extraneous features of the solution. Colloquially, one hopes for an approximate solution that segregates the so-called signal from the noise. This can aid the engineer greatly in building or reinforcing intuition and sometimes lead to a more efficient design and control strategy. In other cases, including those with practical importance, exact solutions are not available. In such cases, engineers often resort to numerically based approximation methods. Indeed, these methods have been established as an essential design tool; however, short of exhaustive parametric studies, it can be difficult to induce significant general insight from numerics alone. Numerical approximation is a broad topic and is not is studied here in any real detail; instead, we focus on analysis-based approximation methods. They do not work for all problems, but in those cases where they do, they are potent aids to the engineer as a predictive tool for design.
Often, though not always, approximation methods rely on some form of linearization to capture the behavior of some local nonlinearity. Such methods are useful in solving algebraic, differential, and integral equations. We begin with a consideration of Taylor series and the closely related Padé approximant. The class of methods we next consider, power series, employed already in Section 4.4 for solutions of ordinary differential equations, is formally exact in that an infinite number of terms can be obtained. Moreover, many such series can be shown to have absolute and uniform convergence properties as well as analytical estimates of errors incurred by truncation at a finite number of terms.