Metabolomics Defines Human Immune Response to Influenza Vaccination

Influenza represents a major and ongoing public health hazard. Current collaborative efforts are aimed at creating a “universal flu vaccine” with the goal of both improving responses to vaccination and increasing the breadth of protection across multiple strains and clades from a single vaccine. As an intermediate step to these goals, current work is focused on evaluating the systemic host response to vaccination in both normal and high-risk populations, such as in obesity which has been linked to poor responses to vaccination. We therefore employed a metabolomics approach using a time-course (n=5 time points) of response to human vaccination to influenza from before vaccination (pre) to 90 days following vaccination. We analyzed both urine and plasma from a cohort of subjects (n=158) designed to evenly sample across age, sex, BMI, and other demographic factors, stratifying their response to vaccination as “High”, “Low”, or “None” based on their measured seroconversion by hemagglutination assay (HAI) from plasma samples at day 28 post vaccination. Overall, we putatively identified 20,692 distinct named small molecules structures across the 790 samples analyzed with the aim of finding metabolite correlates of vaccine response, as well as prognostic and diagnostic markers from before and after vaccination respectively. Notably, subjects classified as obese (BMI \u3e 30) “None” responders were unbiasedly differentiated from obese “High” responders in a hierarchical clustering analysis with 321 statistically significantly significant diagnostic markers in urine 3 days post vaccination (n=45). Considering the comparison of predictive, pre-vaccination samples, a metabolic pathway analysis of the differential markers between “High” and “None” subjects indicates a link to Histidine metabolism and Coenzyme Q10 metabolism. Ongoing efforts are aimed at validating these putative markers in a Ferret model of influenza infection as well as in independent cohorts of human seasonal vaccination and human challenge studies with authentic virus

Results and conjectures on simultaneous core partitions

An n-core partition is an integer partition whose Young diagram contains no hook lengths equal to n. We consider partitions that are simultaneously a-core and b-core for two relatively prime integers a and b. These are related to abacus diagrams and the combinatorics of the affine symmetric group (type A). We observe that self-conjugate simultaneous core partitions correspond to the combinatorics of type C, and use abacus diagrams to unite the discussion of these two sets of objects. In particular, we prove that (2n)- and (2mn+1)-core partitions correspond naturally to dominant alcoves in the m-Shi arrangement of type C_n, generalizing a result of Fishel--Vazirani for type A. We also introduce a major statistic on simultaneous n- and (n+1)-core partitions and on self-conjugate simultaneous (2n)- and (2n+1)-core partitions that yield q-analogues of the Coxeter-Catalan numbers of type A and type C. We present related conjectures and open questions on the average size of a simultaneous core partition, q-analogs of generalized Catalan numbers, and generalizations to other Coxeter groups. We also discuss connections with the cyclic sieving phenomenon and q,t-Catalan numbers.Comment: 17 pages; to appear in the European Journal of Combinatoric

Distribution of LeConte\u27s Free-tailed Bat (Tadarida brasiliensis cynocephala) in Arkansas, with Notes on Reproduction and Natural History

During the past 20 years (1982-2001) we have studied the biology, occurrence and distribution of LeConte\u27s (Brazilian) free-tailed bat, Tadarida brasiliensis cynocephala, in Arkansas. Colonies and individuals were reported from man made structures only. Four new county records have been documented since 1988, extending the range from the central part of the state to Arkansas\u27s northern-most tier of counties. Numerous nuisance maternity colonies were investigated during exclusion activities and one, year-round colony provided the majority of reproductive data. A total of 152 free-tailed bats was submitted to the Arkansas Department of Health Rabies Laboratory (1982-2001); most during February through April, a period that corresponded to annual mating activity. Pregnant bats had single embryos only in the right uterine horn and parturition occurred in mid-June. Seven specimens tested positive for rabies

Variation and interactional non-standardization in neuropsychological tests: The case of the Addenbrooke’s Cognitive Examination

YesThe Addenbrooke’s Cognitive Examination (ACE-111) is a neuropsychological test used in clinical practice to inform a dementia diagnosis. The ACE-111 relies on standardized administration so that patients’ scores can be interpreted by comparison with normative scores. The test is delivered and responded to in interaction between clinicians and patients, which places talk-in-interaction at the heart of its administration. In this article, conversation analysis (CA) is used to investigate how the ACE-111 is delivered in clinical practice. Based on analysis of 40 video/audio-recorded memory clinic consultations in which the ACE-111 was used, we have found that administrative standardization is rarely achieved in practice. There was evidence of both (a) interactional variation in the way the clinicians introduce the test and (b) interactional non-standardization during its implementation. We show that variation and interactional non-standardization have implications for patients’ understanding and how they might respond to particular questions.Partially funded by a grant by the National Institute for Health Research (NIHR) under its Research for Patient Benefit (RfPB) Program (Grant Reference Number PB-PG-0211-24079)

Rapid glutamate receptor 2 trafficking during retinal degeneration

<p>Abstract</p> <p>Background</p> <p>Retinal degenerations, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP), are characterized by photoreceptor loss and anomalous remodeling of the surviving retina that corrupts visual processing and poses a barrier to late-stage therapeutic interventions in particular. However, the molecular events associated with retinal remodeling remain largely unknown. Given our prior evidence of ionotropic glutamate receptor (iGluR) reprogramming in retinal degenerations, we hypothesized that the edited glutamate receptor 2 (GluR2) subunit and its trafficking may be modulated in retinal degenerations.</p> <p>Results</p> <p>Adult albino Balb/C mice were exposed to intense light for 24 h to induce light-induced retinal degeneration (LIRD). We found that prior to the onset of photoreceptor loss, protein levels of GluR2 and related trafficking proteins, including glutamate receptor-interacting protein 1 (GRIP1) and postsynaptic density protein 95 (PSD-95), were rapidly increased. LIRD triggered neuritogenesis in photoreceptor survival regions, where GluR2 and its trafficking proteins were expressed in the anomalous dendrites. Immunoprecipitation analysis showed interaction between KIF3A and GRIP1 as well as PSD-95, suggesting that KIF3A may mediate transport of GluR2 and its trafficking proteins to the novel dendrites. However, in areas of photoreceptor loss, GluR2 along with its trafficking proteins nearly vanished in retracted retinal neurites.</p> <p>Conclusions</p> <p>All together, LIRD rapidly triggers GluR2 plasticity, which is a potential mechanism behind functionally phenotypic revisions of retinal neurons and neuritogenesis during retinal degenerations.</p

H α fluxes and extinction distances for planetary nebulae in the IPHAS survey of the northern galactic plane

We report H α filter photometry for 197 Northern hemisphere planetary nebulae (PNe) obtained using imaging data from the IPHAS survey. H α+[N II] fluxes were measured for 46 confirmed or possible PNe discovered by the IPHAS survey and for 151 previously catalogued PNe that fell within the area of the northern Galactic Plane surveyed by IPHAS. After correcting for [N II] emission admitted by the IPHAS H α filter, the resulting H α fluxes were combined with published radio free–free fluxes and H β fluxes, in order to estimate mean optical extinctions to 143 PNe using ratios involving their integrated Balmer line fluxes and their extinction-free radio fluxes. Distances to the PNe were then estimated using three different 3D interstellar dust extinction mapping methods, including the IPHAS-based H-MEAD algorithm of Sale (2014). These methods were used to plot dust extinction versus distance relationships for the lines of sight to the PNe; the intercepts with the derived dust optical extinctions allowed distances to the PNe to be inferred. For 17 of the PNe in our sample reliable GaiaDR2 distances were available and these have been compared with the distances derived using three different extinction mapping algorithms as well as with distances from the nebular radius versus H α surface brightness relation of Frew et al. (2016). That relation and the H-MEAD extinction mapping algorithm yielded the closest agreement with the Gaia DR2 distances

The societal cost of Huntington’s disease:are we underestimating the burden?

Background and purpose Approximately 9000 people in the UK are affected by Huntington's disease (HD). People with HD require ongoing health and social care support. There is a knowledge gap about costs of health and social care use associated with HD in the UK. This paper estimates the economic cost in the UK. Methods Data on UK patients for the year 2013 were extracted from the European Huntington's Disease Network REGISTRY study, a full clinical dataset, including the full medical history and medication history for patients with HD. National unit costs for the price year 2013 were applied to health and social care services. Results Data were available for 131 people. The mean annual cost per person with HD was £21 605. The largest proportion of this cost (65%) was due to informal care (£14 085). Conclusions Informal care was the largest driver of costs across all stages of HD; thus there is a need to also consider the needs of carers when planning services for people with HD

Truncating the Y-Axis: Threat or Menace?

Bar charts with y-axes that don't begin at zero can visually exaggerate effect sizes. However, advice for whether or not to truncate the y-axis can be equivocal for other visualization types. In this paper we present examples of visualizations where this y-axis truncation can be beneficial as well as harmful, depending on the communicative and analytic intent. We also present the results of a series of crowd-sourced experiments in which we examine how y-axis truncation impacts subjective effect size across visualization types, and we explore alternative designs that more directly alert viewers to this truncation. We find that the subjective impact of axis truncation is persistent across visualizations designs, even for designs with explicit visual cues that indicate truncation has taken place. We suggest that designers consider the scale of the meaningful effect sizes and variation they intend to communicate, regardless of the visual encoding

Zoonosis emergence linked to agricultural intensification and environmental change

A systematic review was conducted by a multidisciplinary team to analyze qualitatively best available scientific evidence on the effect of agricultural intensification and environmental changes on the risk of zoonoses for which there are epidemiological interactions between wildlife and livestock. The study found several examples in which agricultural intensification and/or environmental change were associated with an increased risk of zoonotic disease emergence, driven by the impact of an expanding human population and changing human behavior on the environment. We conclude that the rate of future zoonotic disease emergence or reemergence will be closely linked to the evolution of the agriculture–environment nexus. However, available research inadequately addresses the complexity and interrelatedness of environmental, biological, economic, and social dimensions of zoonotic pathogen emergence, which significantly limits our ability to predict, prevent, and respond to zoonotic disease emergence