Vection in depth during consistent and inconsistent multisensory stimulation

We examined vection induced during physical or simulated head oscillation along either the horizontal or depth axis. In the first two experiments, during active conditions, subjects viewed radial-flow displays which simulated viewpoint oscillation that was either in-phase or out-of-phase with their own tracked head movements. In passive conditions, stationary subjects viewed playbacks of displays generated in earlier active conditions. A third control, experiment was also conducted where physical and simulated fore ^ aft oscillation was added to a lamellar flow display. Consistent with ecology, when active in-phase horizontal oscillation was added to a radial-flow display it modestly improved vection compared to active out-of-phase and passive conditions. However, when active fore ^ aft head movements were added to either a radial-flow or a lamellar-flow display, both in-phase and out-of-phase conditions produced very similar vection. Our research shows that consistent multisensory input can enhance the visual perception of self- motion in some situations. However, it is clear that multisensory stimulation does not have to be consistent (ie ecological) to generate compelling vection in depth

Dietary supplementation with Bifidobacterium longum subsp. infantis (B. infantis) in healthy breastfed infants: study protocol for a randomised controlled trial.

BackgroundThe development of probiotics as therapies to cure or prevent disease lags far behind that of other investigational medications. Rigorously designed phase I clinical trials are nearly non-existent in the field of probiotic research, which is a contributing factor to this disparity. As a consequence, how to appropriately dose probiotics to study their efficacy is unknown. Herein we propose a novel phase I ascending dose trial of Bifidobacterium longum subsp. infantis (B. infantis) to identify the dose required to produce predominant gut colonisation in healthy breastfed infants at 6 weeks of age.Methods/designThis is a parallel-group, placebo-controlled, randomised, double-blind ascending dose phase I clinical trial of dietary supplementation with B. infantis in healthy breastfed infants. The objective is to determine the pharmacologically effective dose (ED) of B. infantis required to produce predominant (>50 %) gut colonisation in breastfed infants at 6 weeks of age. Successively enrolled infant groups will be randomised to receive two doses of either B. infantis or placebo on days 7 and 14 of life. Stool samples will be used to characterise the gut microbiota at increasing doses of B. infantis.DiscussionProbiotic supplementation has shown promising results for the treatment of a variety of ailments, but evidence-based dosing regimes are currently lacking. The ultimate goal of this trial is to establish a recommended starting dose of B. infantis for further efficacy-testing phase II trials designed to evaluate B. infantis for the prevention of atopic dermatitis and food allergies in at-risk children.Trial registrationClinicaltrials.gov # NCT02286999 , date of trial registration 23 October 2014

Similarity of Recombinant Human Perlecan Domain 1 by Alternative Expression Systems Bioactive Heterogenous Recombinant Human Perlecan D1

<p>Abstract</p> <p>Background</p> <p>Heparan sulfate glycosaminoglycans are diverse components of certain proteoglycans and are known to interact with growth factors as a co-receptor necessary to induce signalling and growth factor activity. In this report we characterize heterogeneously glycosylated recombinant human perlecan domain 1 (HSPG2 abbreviated as rhPln.D1) synthesized in either HEK 293 cells or HUVECs by transient gene delivery using either adenoviral or expression plasmid technology.</p> <p>Results</p> <p>By SDS-PAGE analysis following anion exchange chromatography, the recombinant proteoglycans appeared to possess glycosaminoglycan chains ranging, in total, from 6 kDa to >90 kDa per recombinant. Immunoblot analysis of enzyme-digested high M_rrhPln.D1 demonstrated that the rhPln.D1 was synthesized as either a chondroitin sulfate or heparan sulfate proteoglycan, in an approximately 2:1 ratio, with negligible hybrids. Secondary structure analysis suggested helices and sheets in both recombinant species. rhPln.D1 demonstrated binding to rhFGF-2 with an apparent k_Dof 2 ± 0.2 nM with almost complete susceptibility to digestion by heparinase III in ligand blot analysis but not to chondroitinase digestion. Additionally, we demonstrate HS-mediated binding of both rhPln.D1 species to several other GFs. Finally, we corroborate the augmentation of FGF-mediated cell activation by rhPln.D1 and demonstrate mitogenic signalling through the FGFR1c receptor.</p> <p>Conclusions</p> <p>With importance especially to the emerging field of DNA-based therapeutics, we have shown here that proteoglycan synthesis, in different cell lines where GAG profiles typically differ, can be directed by recombinant technology to produce populations of bioactive recombinants with highly similar GAG profiles.</p

Low usage of government healthcare facilities for acute respiratory infections in guatemala: implications for influenza surveillance

<p>Abstract</p> <p>Background</p> <p>Sentinel surveillance for severe acute respiratory infections in hospitals and influenza-like illness in ambulatory clinics is recommended to assist in global pandemic influenza preparedness. Healthcare utilization patterns will affect the generalizability of data from sentinel sites and the potential to use them to estimate burden of disease. The objective of this study was to measure healthcare utilization patterns in Guatemala to inform the establishment of a sentinel surveillance system for influenza and other respiratory infections, and allow estimation of disease burden.</p> <p>Methods</p> <p>We used a stratified, two-stage cluster survey sample to select 1200 households from the Department of Santa Rosa. Trained interviewers screened household residents for self-reported pneumonia in the last year and influenza-like illness (ILI) in the last month and asked about healthcare utilization for each illness episode.</p> <p>Results</p> <p>We surveyed 1131 (94%) households and 5449 residents between October and December 2006 and identified 323 (6%) cases of pneumonia and 628 (13%) cases of ILI. Treatment for pneumonia outside the home was sought by 92% of the children <5 years old and 73% of the persons aged five years and older. For both children <5 years old (53%) and persons aged five years and older (31%) who reported pneumonia, private clinics were the most frequently reported source of care. For ILI, treatment was sought outside the home by 81% of children <5 years old and 65% of persons aged five years and older. Government ambulatory clinics were the most frequently sought source of care for ILI both for children <5 years old (41%) and persons aged five years and older (36%).</p> <p>Conclusions</p> <p>Sentinel surveillance for influenza and other respiratory infections based in government health facilities in Guatemala will significantly underestimate the burden of disease. Adjustment for healthcare utilization practices will permit more accurate estimation of the incidence of influenza and other respiratory pathogens in the community.</p

Fairness-Aware Graph Neural Networks: A Survey

Graph Neural Networks (GNNs) have become increasingly important due to their representational power and state-of-the-art predictive performance on many fundamental learning tasks. Despite this success, GNNs suffer from fairness issues that arise as a result of the underlying graph data and the fundamental aggregation mechanism that lies at the heart of the large class of GNN models. In this article, we examine and categorize fairness techniques for improving the fairness of GNNs. Previous work on fair GNN models and techniques are discussed in terms of whether they focus on improving fairness during a preprocessing step, during training, or in a post-processing phase. Furthermore, we discuss how such techniques can be used together whenever appropriate, and highlight the advantages and intuition as well. We also introduce an intuitive taxonomy for fairness evaluation metrics including graph-level fairness, neighborhood-level fairness, embedding-level fairness, and prediction-level fairness metrics. In addition, graph datasets that are useful for benchmarking the fairness of GNN models are summarized succinctly. Finally, we highlight key open problems and challenges that remain to be addressed

Racial Differences in Abnormal Ambulatory Blood Pressure Monitoring Measures: Results From the Coronary Artery Risk Development in Young Adults (CARDIA) Study

Background: Several ambulatory blood pressure monitoring (ABPM) measures have been associated with increased cardiovascular disease risk independent of clinic blood pressure (BP). African Americans have higher clinic BP compared with Whites but few data are available on racial differences in ABPM measures. Methods: We compared ABPM measures between African American (n = 178) and White (n = 103) participants at the Year 5 Coronary Artery Risk Development in Young Adults study visit. BP was measured during a study visit and the second and third measurements were averaged. ABPM was conducted over the following 24 hours. Results: Mean ± SD age of participants was 29.8±3.8 years and 30.8±3.5 years for African Americans and Whites, respectively. Mean daytime systolic BP (SBP) was 3.90 (SD 1.18) mm Hg higher among African Americans compared with Whites (P < 0.001) after age–gender adjustment and 1.71 (SD 1.03) mm Hg higher after multivariable adjustment including mean clinic SBP (P = 0.10). After multivariable adjustment including mean clinic SBP, nighttime SBP was 4.83 (SD 1.11) mm Hg higher among African Americans compared with Whites (P < 0.001). After multivariable adjustment, the African Americans were more likely than Whites to have nocturnal hypertension (prevalence ratio: 2.44, 95% CI: 0.99–6.05) and nondipping (prevalence ratio: 2.50, 95% CI: 1.39–4.48). The prevalence of masked hypertension among African Americans and Whites was 4.4% and 2.1%, respectively, (P = 0.49) and white coat hypertension was 3.3% and 3.9%, respectively (P = 0.99). Twenty-four hour BP variability on ABPM was higher among African Americans compared with Whites. Conclusions: These data suggest racial differences in several ABPM measures exist

Evidence that the rat osteopetrotic mutation toothless (tl) is not in the TNFSF11 (TRANCE, RANKL, ODF, OPGL) gene

The toothless (tl) osteopetrotic mutation in the rat affects an osteoblast-derived factor that is required for normal osteoclast differentiation. Although the genetic locus remains unknown, the phenotypic impact of the tl mutation on multiple systems has been well characterized. Some of its actions are similar to tumornecrosis factor superfamily member 11(TNFSF11; also called TRANCE, RANKL, ODF and OPGL) null mice. TNFSF11 is a recently described member of the tumor necrosis factor superfamily which, when expressed by activated T cells, enhances the survival of antigen-presenting dendritic cells, and when expressed by osteoblasts, promotes the differentiation and activation of osteoclasts. The skeletal similarities between tl rats and TNFSF11(-/-) mice include 1) profound osteoclastopenia (TNFSF11-null mice, 0% and tl rats 0-1% of normal); 2) persistent, non-resolving osteopetrosis that results from 3) a defect not in the osteoclast lineage itself, but in an osteoblast-derived, osteoclastogenic signal; and 4) a severe chondrodysplasia of the growth plates of long bones not seen in other osteopetrotic mutations. The latter includes thickening of the growth plate with age, disorganization of chondrocyte columns, and disturbances of chondrocyte maturation. These striking similarities prompted us to undertake studies to rule in or out a TNFSF11 mutation in the tl rat. We looked for expression of TNFSF11 mRNA in tl long bones and found it to be over-expressed and of the correct size. We also tested TNFSF11 protein function in the tl rat. This was shown to be normal by flow cytometry experiments in which activated, spleen-derived T-cells from tl rats exhibited normal receptor binding competence, as measured by a recombinant receptor assay. We also found that tl rats develop histologically normal mesenteric and peripheral lymph nodes, which are absent from TNFSF11-null mice. Next, we found that injections of recombinant TNFSF11, which restores bone resorption in null mice, had no therapeutic effect in tl rats. Finally, gene mapping studies using co-segregation of polymorphic markers excluded the chromosomal region containing the TNFSF11 gene as harboring the mutation responsible for the tl phenotype. We conclude that, despite substantial phenotypic similarities to TNFSF11(-/-) mice, the tl rat mutation is not in the TNFSF11 locus, and that its identification must await the results of further studies