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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
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.
The following acknowledgement was omitted from the original publication:
The authors would like to acknowledge the support of the BBSRC (The Biotechnology and Biosciences Research Council) for the funding of IKnowFood at York which is 4-year research programme being funded through the Global Food Security-Food System Resilience programme with contributions from BBSRC, ESRC, NERC, and the Scottish Government.
This paper derives from a study of community food aid in a multi-ethnic, multi-faith city in the North of England. The paper begins to make sense of the diversity of types of food insecurity assistance, examines the potential exclusion of certain groups from receipt of food aid, and explores the relationship between food aid providers and the state. Faith-based food aid is common in the case study area, particularly among food bank provision to the most ‘destitute’ clients. While food aid is adopting service responsibilities previously borne by the state, this does not imply an extension of the ‘shadow state’. Rather, it appears reflective of a pre-welfare state system of food distribution, supported by religious institutions and individual/business philanthropy, but adapted to be consistent with elements of the ‘Big Society’ narrative. Most faith-based providers are Christian. There is little Muslim provision of (or utilisation of) food aid, despite the local demographic context. This raises concerns as to the unintentional exclusion of ethnic and religious groups, which we discuss in the concluding sections.
Mealtime interventions typically focus on institutionalised older adults, but we wanted to investigate whether they may also be effective among those living independently. Using a randomised controlled trial design, we assessed the effects of a novel mealtime intervention on self-efficacy, food enjoyment and energy intake. A total of 100 adults living alone aged over 60 years were randomised to the treatment or control conditions: all received a guidebook on nutrition and culinary skills. Treatment group participants received a weekly visit from a trained volunteer who prepared and shared a meal with them. Participants in the treatment group showed improvements relative to those in the control group at borderline significance (P=0·054) for self-efficacy and at significance for food enjoyment. Significant improvements were observed in female participants in the treatment but not in the control group in energy intake (although following corrections for multiple comparisons, only the effect on food enjoyment remained significant). These findings will inform the design of future complex interventions. For this type of intervention to be successful, more focus has to be placed on making interventions more personalised, potentially according to sex. Findings are important for nutritional sciences as they indicate that, in order to improve energy intake and food enjoyment among older adults, multimodal nutritional interventions including social components may be successful.
This review essay critically examines the evolution of scholarly literature on Brazil's Partido dos Trabalhadores since the PT's founding in 1980. We periodise the relevant literature into four phases, examining the foundation of the PT, the party's early experience in subnational government, its transformation and moderation in the late 1990s, and finally its experiences in national government since capturing the presidency in 2002. After detailing strengths and weaknesses of this research, we also examine the trajectory of the PT in light of recent comparative work on the so-called ‘left turn’ in Latin America. We conclude by offering an agenda for future research on the PT.
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.
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.
We consider two-dimensional one-sided convection of a solute in a fluid-saturated porous medium, where the solute decays via a first-order reaction. Fully nonlinear convection is investigated using high-resolution numerical simulations and a low-order model that couples the dynamic boundary layer immediately beneath the distributed solute source to the slender vertical plumes that form beneath. A transient-growth analysis of the boundary layer is used to characterise its excitability. Three asymptotic regimes are investigated in the limit of high Rayleigh number
, in which the domain is considered deep, shallow or of intermediate depth, and for which the Damköhler number
is respectively large, small or of order unity. Scaling properties of the flow are identified numerically and rationalised via the analytic model. For fully established high-
convection, analysis and simulation suggest that the time-averaged solute transfer rate scales with
and the plume horizontal wavenumber with
, with coefficients modulated by
in each case. For large
, the rapid reaction rate limits the plume depth and the boundary layer restricts the rate of solute transfer to the bulk, whereas for small
the average solute transfer rate is ultimately limited by the domain depth and the convection is correspondingly weaker.
Motivated by processes occurring during
sequestration in an underground saline aquifer, we examine two-dimensional convection in a finite-depth porous medium induced by a solute introduced at the upper boundary. Once dissolved, the solute concentration is assumed to decay via a first-order chemical reaction, restricting the depth over which solute can penetrate the domain. Using spectral and asymptotic methods, we explore the resulting convective mixing using linear stability analysis, computation of nonlinear steady solution branches and time-dependent simulations, as a function of Rayleigh number, Damköhler number and domain size. Long-wave eigenmodes show how deep recirculation can be driven by a shallow solute field while explicit approximations are derived for the growth of short-wave eigenmodes. Steady solution branches undergo numerous secondary bifurcations, forming an intricate network of mixed states. Although many of these states are unstable, some play an important role in organising the phase space of time-dependent states, providing approximate bounds for time-averaged mixing rates.
Fire is one of the most important natural disturbances in the coniferous forests of the US Rocky Mountains. The Rocky Mountains are separated by a climatic boundary between 40° and 45° N, which we refer to as the central Rocky Mountains (CRM). To determine whether the fire regime from the CRM was more similar to the northern Rocky Mountains (NRM) or southern Rocky Mountains (SRM) during the Holocene, a 12,539-yr-old sediment core from Long Lake, Wyoming, located in the CRM was analyzed for charcoal and pollen. These data were then compared to charcoal records from the CRM, NRM and SRM. During the Younger Dryas chronozone, the fire regime was characterized as frequent at Long Lake. The early and middle Holocene fire regime was characterized as infrequent. A brief interval from 4000 to 3000 cal yr BP, termed the Populus period, had a frequent fire regime and remained frequent through the late Holocene at Long Lake. In comparison to sites from the NRM and SRM, the fire regime at Long Lake was most similar to the SRM during the past 12,539 cal yr BP. These results suggest the disturbance regime in the CRM has a greater affinity with those of the SRM.
The human intestine is colonised by 1013 to 1014 micro-organisms, the vast majority of which belong to the phyla Firmicutes and Bacteroidetes. Although highly stable over time, the composition and activities of the microbiota may be influenced by a number of factors including age, diet and antibiotic treatment. Although perturbations in the composition or functions of the microbiota are linked to inflammatory and metabolic disorders (e.g. inflammatory bowel diseases, irritable bowel syndrome and obesity), it is unclear at this point whether these changes are a symptom of the disease or a contributing factor. A better knowledge of the mechanisms through which changes in microbiota composition (dysbiosis) promote disease states is needed to improve our understanding of the causal relationship between the gut microbiota and disease. While evidence of the preventive and therapeutic effects of probiotic strains on diarrhoeal illness and other intestinal conditions is promising, the exact mechanisms of the beneficial effects are not fully understood. Recent studies have raised the question of whether non-viable probiotic strains can confer health benefits on the host by influencing the immune system. As the potential health effect of these non-viable bacteria depends on whether the mechanism of this effect is dependent on viability, future research needs to consider each probiotic strain on a case-by-case basis. The present review provides a comprehensive, updated overview of the human gut microbiota, the factors influencing its composition and the role of probiotics as a therapeutic modality in the treatment and prevention of diseases and/or restoration of human health.
The future of centimetre and metre-wave astronomy lies with the Square Kilometre Array (SKA), a telescope under development by a consortium of 17 countries that will be 50 times more sensitive than any existing radio facility. Most of the key science for the SKA will be addressed through large-area imaging of the Universe at frequencies from a few hundred MHz to a few GHz. The Australian SKA Pathfinder (ASKAP) is a technology demonstrator aimed in the mid-frequency range, and achieves instantaneous wide-area imaging through the development and deployment of phased-array feed systems on parabolic reflectors. The large field-of-view makes ASKAP an unprecedented synoptic telescope that will make substantial advances in SKA key science. ASKAP will be located at the Murchison Radio Observatory in inland Western Australia, one of the most radio-quiet locations on the Earth and one of two sites selected by the international community as a potential location for the SKA. In this paper, we outline an ambitious science program for ASKAP, examining key science such as understanding the evolution, formation and population of galaxies including our own, understanding the magnetic Universe, revealing the transient radio sky and searching for gravitational waves.
This chapter focuses on aspects of structural and functional neuroanatomy relevant to Behavioral Neurology & Neuropsychiatry (BN&NP). It considers the general structure of the brain from the brainstem through the cerebral cortex, including a review of white matter anatomy, the cerebral vasculature, and the ventricular system. The brainstem comprises the medulla oblongata, pons and cerebellum, and midbrain. Each of these areas and the neurobehaviorally salient structures they contain are reviewed briefly in the chapter. The reticular formation (which is contributed to by several brainstem substructures) and the cranial nerves (some, but not all, of which are located within the brainstem) also are discussed in the chapter. The diencephalon includes the thalamus, metathalamus (medial and lateral geniculate nuclei), epithalamus (habenula, stria medullaris, and pineal body), and subthalamus. The chapter considers briefly the thalamus, hypothalamus (and pituitary), and the epithalamus.