On the Price of Anarchy of Highly Congested Nonatomic Network Games

We consider nonatomic network games with one source and one destination. We examine the asymptotic behavior of the price of anarchy as the inflow increases. In accordance with some empirical observations, we show that, under suitable conditions, the price of anarchy is asymptotic to one. We show with some counterexamples that this is not always the case. The counterexamples occur in very simple parallel graphs.Comment: 26 pages, 6 figure

The contribution of diet and genotype to iron status in women:a classical twin study

This is the first published report examining the combined effect of diet and genotype on body iron content using a classical twin study design. The aim of this study was to determine the relative contribution of genetic and environmental factors in determining iron status. The population was comprised of 200 BMI- and age-matched pairs of MZ and DZ healthy twins, characterised for habitual diet and 15 iron-related candidate genetic markers. Variance components analysis demonstrated that the heritability of serum ferritin (SF) and soluble transferrin receptor was 44% and 54% respectively. Measured single nucleotide polymorphisms explained 5% and selected dietary factors 6% of the variance in iron status; there was a negative association between calcium intake and body iron (p = 0.02) and SF (p = 0.04)

OMERACT Filter 2.1: Elaboration of the Conceptual Framework for Outcome Measurement in Health Intervention Studies

Objective: The Outcome Measures in Rheumatology (OMERACT) Filter 2.0 framework was developed in 2014 to aid core outcome set development by describing the full universe of “measurable aspects of health conditions” from which core domains can be selected. This paper provides elaborations and updated concepts (OMERACT Filter 2.1). Methods: At OMERACT 2018, we discussed challenges in the framework application caused by unclear or ambiguous wording and terms and incompletely developed concepts. Results: The updated OMERACT Filter 2.1 framework makes benefits and harms explicit, clarifies concepts, and improves naming of various terms. Conclusion: We expect that the Filter 2.1 framework will improve the process of core set development

A demonstration of 'broken' visual space

It has long been assumed that there is a distorted mapping between real and ‘perceived’ space, based on demonstrations of systematic errors in judgements of slant, curvature, direction and separation. Here, we have applied a direct test to the notion of a coherent visual space. In an immersive virtual environment, participants judged the relative distance of two squares displayed in separate intervals. On some trials, the virtual scene expanded by a factor of four between intervals although, in line with recent results, participants did not report any noticeable change in the scene. We found that there was no consistent depth ordering of objects that can explain the distance matches participants made in this environment (e.g. A > B > D yet also A < C < D) and hence no single one-to-one mapping between participants’ perceived space and any real 3D environment. Instead, factors that affect pairwise comparisons of distances dictate participants’ performance. These data contradict, more directly than previous experiments, the idea that the visual system builds and uses a coherent 3D internal representation of a scene

Undifferentiated spondyloarthritis following allogeneic stem cell transplantation

<p>Abstract</p> <p>Background</p> <p>Stem cell transplant has been utilized in the treatment of malignancies and rheumatic disease. Rheumatic disease may be transferred from the donor with active disease or may be developed in a recipient de novo as a late complication of SCT.</p> <p>Case Presentation</p> <p>We here report the rare case of a 26-year old male patient, who has been diagnosed with undifferentiated spondyloarthropathy after unique circumstance. The patient suffered from intermittent inflammatory back pain and peripheral joint swelling for several years and did not find relief through multiple emergency room visits at different medical facilities. After a thorough history and physical exam, it was noted that our patient had developed signs of axial disease along with dactylitis and overall that he had been insidiously developing an undifferentiated spondyloarthopathy after allogeneic stem cell transplantation.</p> <p>Conclusion</p> <p>Our observation supports the hypothesis that de novo rheumatic disease can develop after stem cell transplant for a variety of reasons. Thus, larger studies and awareness of this association are needed to delineate the exact underlying mechanism(s).</p

Dietary antioxidant intake and the risk of developing Barrett’s oesophagus and oesophageal adenocarcinoma

Background: We investigated in a cohort study, for the first time using 7-day food diaries (7-DFDs), for age-dependent inverse associations with antioxidants, which have anti-carcinogenic properties, and development of Barrett’s oesophagus (BO) and oesophageal adenocarcinoma (OAC). Methods: A total of 24,068 well individuals completed 7-DFDs and donated blood. Vitamins C and E, carotenes, zinc and selenium intakes, and plasma vitamin C were measured. Participants were monitored for 15 years for BO and OAC. Hazard ratios (HRs) were estimated for: quintiles of intake and in participants younger and >=65 years at recruitment, the midpoint of BO peak prevalence. Results: A total of 197 participants developed BO and 74 OAC. There were no significant associations between antioxidants and BO or OAC in the whole cohort or if >65 years at recruitment. In participants <65 years, for BO, there was an inverse trend across plasma vitamin C quintiles (trend HR = 0.82; 95% CI = 0.71–0.96, P = 0.01), OAC for plasma vitamin C (trend HR = 0.58; 95% CI = 0.37–0.92, P = 0.02) and for dietary vitamins C and E (trend HR = 0.71 95% CI = 0.51–0.99, P = 0.04 and trend HR = 0.70; 95% CI = 0.51–0.96; P = 0.03). Conclusions: Data supports a role for dietary antioxidants prevent BO and OAC, perhaps at the earlier stages of carcinogenesis

ZPS: visualization of recent adaptive evolution of proteins

<p>Abstract</p> <p>Background</p> <p>Detection of adaptive amino acid changes in proteins under recent short-term selection is of great interest for researchers studying microevolutionary processes in microbial pathogens or any other biological species. However, independent occurrence of such point mutations within genetically diverse haplotypes makes it difficult to detect the selection footprint by using traditional molecular evolutionary analyses. The recently developed Zonal Phylogeny (ZP) has been shown to be a useful analytic tool for identifying the footprints of short-term positive selection. ZP separates protein-encoding genes into evolutionarily long-term (with silent diversity) and short-term (without silent diversity) categories, or zones, followed by statistical analysis to detect signs of positive selection in the short-term zone. However, successful broad application of ZP for analysis of large haplotype datasets requires automation of the relatively labor-intensive computational process.</p> <p>Results</p> <p>Here we present Zonal Phylogeny Software (ZPS), an application that describes the distribution of single nucleotide polymorphisms (SNPs) of synonymous (silent) and non-synonymous (replacement) nature along branches of the DNA tree for any given protein-coding gene locus. Based on this information, ZPS separates the protein variant haplotypes with silent variability (Primary zone) from those that have recently evolved from the Primary zone variants by amino acid changes (External zone). Further comparative analysis of mutational hot-spot frequencies and haplotype diversity between the two zones allows determination of whether the External zone haplotypes emerged under positive selection.</p> <p>Conclusions</p> <p>As a visualization tool, ZPS depicts the protein tree in a DNA tree, indicating the most parsimonious numbers of synonymous and non-synonymous changes along the branches of a maximum-likelihood based DNA tree, along with information on homoplasy, reversion and structural mutation hot-spots. Through zonal differentiation, ZPS allows detection of recent adaptive evolution via selection of advantageous structural mutations, even when the advantage conferred by such mutations is relatively short-term (as in the case of "source-sink" evolutionary dynamics, which may represent a major mode of virulence evolution in microbes).</p

Dietary fibre intake and risk of ischaemic and haemorrhagic stroke in the UK Women’s Cohort Study

BACKGROUND: Stroke risk is modifiable through many risk factors, one being healthy dietary habits. Fibre intake was associated with a reduced stroke risk in recent meta-analyses; however, data were contributed by relatively few studies, and few examined different stroke types. METHODS: A total of 27 373 disease-free women were followed up for 14.4 years. Diet was assessed with a 217-item food frequency questionnaire and stroke cases were identified using English Hospital Episode Statistics and mortality records. Survival analysis was applied to assess the risk of total, ischaemic or haemorrhagic stroke in relation to fibre intake. RESULTS: A total of 135 haemorrhagic and 184 ischaemic stroke cases were identified in addition to 138 cases where the stroke type was unknown or not recorded. Greater intake of total fibre, higher fibre density and greater soluble fibre, insoluble fibre and fibre from cereals were associated with a significantly lower risk for total stroke. For total stroke, the hazard ratio per 6 g/day total fibre intake was 0.89 (95% confidence intervals: 0.81–0.99). Different findings were observed for haemorrhagic and ischaemic stroke in healthy-weight or overweight women. Total fibre, insoluble fibre and cereal fibre were inversely associated with haemorrhagic stroke risk in overweight/obese participants, and in healthy-weight women greater cereal fibre was associated with a lower ischaemic stroke risk. In non-hypertensive women, higher fibre density was associated with lower ischaemic stroke risk. CONCLUSIONS: Greater total fibre and fibre from cereals are associated with a lower stroke risk, and associations were more consistent with ischaemic stroke. The different observations by stroke type, body mass index group or hypertensive status indicates potentially different mechanisms

Towards an ecology of participation: Process philosophy and co-creation of higher education curricula

This article brings together the authors' previous work on co-created curricula (Bovill et al., 2011; Bovill, 2013a; Bovill, 2014) and on partnership and ethics (Taylor and Robinson, 2014; Taylor, 2015), to develop the concept of co-created curricula as an ecology of participation. In doing so, it deploys Alfred North Whitehead’s process philosophy to formulate a new way of considering co-creation in the curriculum and co-creation of the curriculum in higher education. Two empirical examples are used to illuminate what such an approach offers. From this, we outline three dimensions of an ecology of participation: a process of becoming which recasts subjectivity; acting well in relation which enacts concern; and an orientation to harmony in which difference in equality is valued. The contribution of the article is twofold: first, the concept of an ecology of participation takes forward current thinking on higher education curricula and partnership ethics; second, its use of process philosophy provides a new lens to consider co-creation in the curriculum and co-creation of the curriculum

Genome-regulated Assembly of a ssRNA Virus May Also Prepare It for Infection.

Many single-stranded, positive-sense RNA viruses regulate assembly of their infectious virions by forming multiple, cognate coat protein (CP)-genome contacts at sites termed Packaging Signals (PSs). We have determined the secondary structures of the bacteriophage MS2 ssRNA genome (gRNA) frozen in defined states using constraints from X-ray synchrotron footprinting (XRF). Comparison of the footprints from phage and transcript confirms the presence of multiple PSs in contact with CP dimers in the former. This is also true for a virus-like particle (VLP) assembled around the gRNA in vitro in the absence of the single-copy Maturation Protein (MP) found in phage. Since PS folds are present at many sites across gRNA transcripts, it appears that this genome has evolved to facilitate this mechanism of assembly regulation. There are striking differences between the gRNA-CP contacts seen in phage and the VLP, suggesting that the latter are inappropriate surrogates for aspects of phage structure/function. Roughly 50% of potential PS sites in the gRNA are not in contact with the protein shell of phage. However, many of these sit adjacent to, albeit not in contact with, PS-binding sites on CP dimers. We hypothesize that these act as PSs transiently during assembly but subsequently dissociate. Combining the XRF data with PS locations from an asymmetric cryo-EM reconstruction suggests that the genome positions of such dissociations are non-random and may facilitate infection. The loss of many PS-CP interactions towards the 3′ end of the gRNA would allow this part of the genome to transit more easily through the narrow basal body of the pilus extruding machinery. This is the known first step in phage infection. In addition, each PS-CP dissociation event leaves the protein partner trapped in a non-lowest free-energy conformation. This destabilizes the protein shell which must disassemble during infection, further facilitating this stage of the life-cycle