Variation in lung function as a marker of adherence to oral and inhaled medication in cystic fibrosis

Study aim: The aim of this study was to characterise adherence in an adult population with CF and to investigate if variation in lung function was a predictor of adherence to treatment. Patients and methods: Patients aged ≥ 16 years from an adult CF centre undertook adherence measures by medication possession ratio (MPR) and self-report and were assigned to one of three adherence categories (<50%, 50-<80%, 80% and above) by their composite score (MPR). Ordinal regression was used to identify predictors of adherence including coefficient variation measures for forced expiratory volume in 1 second (FEV1), weight and C-reactive protein, measured up to 6 and 12 months. Results: MPR data for 106 of 249 patients [mean age 29.8 (±9.2) years] was retrieved, indicating a mean adherence of 63%. Coefficient of variation FEV1 was inversely related to adherence and was a univariate predictor of adherence (6 months: 0.92 [0.87-0.98] p= 0.005 and 12 months: 0.94 [0.93-0.99], p=0.03]) and remained significant in the final models. The coefficient variation of weight and C-reactive protein were not predictive of adherence. Conclusions: Coefficient of variation FEV1 was identified as an objective predictor of adherence. Further evaluation of this potential marker of adherence is now required

Rich Situated Attitudes

We outline a novel theory of natural language meaning, Rich Situated Semantics [RSS], on which the content of sentential utterances is semantically rich and informationally situated. In virtue of its situatedness, an utterance’s rich situated content varies with the informational situation of the cognitive agent interpreting the utterance. In virtue of its richness, this content contains information beyond the utterance’s lexically encoded information. The agent-dependence of rich situated content solves a number of problems in semantics and the philosophy of language (cf. [14, 20, 25]). In particular, since RSS varies the granularity of utterance contents with the interpreting agent’s informational situation, it solves the problem of finding suitably fine- or coarse-grained objects for the content of propositional attitudes. In virtue of this variation, a layman will reason with more propositions than an expert

Accurate reconstruction of insertion-deletion histories by statistical phylogenetics

The Multiple Sequence Alignment (MSA) is a computational abstraction that represents a partial summary either of indel history, or of structural similarity. Taking the former view (indel history), it is possible to use formal automata theory to generalize the phylogenetic likelihood framework for finite substitution models (Dayhoff's probability matrices and Felsenstein's pruning algorithm) to arbitrary-length sequences. In this paper, we report results of a simulation-based benchmark of several methods for reconstruction of indel history. The methods tested include a relatively new algorithm for statistical marginalization of MSAs that sums over a stochastically-sampled ensemble of the most probable evolutionary histories. For mammalian evolutionary parameters on several different trees, the single most likely history sampled by our algorithm appears less biased than histories reconstructed by other MSA methods. The algorithm can also be used for alignment-free inference, where the MSA is explicitly summed out of the analysis. As an illustration of our method, we discuss reconstruction of the evolutionary histories of human protein-coding genes.Comment: 28 pages, 15 figures. arXiv admin note: text overlap with arXiv:1103.434

Genome-Wide Association Studies of Cognitive and Motor Progression in Parkinson's Disease

BACKGROUND: There are currently no treatments that stop or slow the progression of Parkinson's disease (PD). Case-control genome-wide association studies have identified variants associated with disease risk, but not progression. The objective of the current study was to identify genetic variants associated with PD progression. METHODS: We analyzed 3 large longitudinal cohorts: Tracking Parkinson's, Oxford Discovery, and the Parkinson's Progression Markers Initiative. We included clinical data for 3364 patients with 12,144 observations (mean follow-up 4.2 years). We used a new method in PD, following a similar approach in Huntington's disease, in which we combined multiple assessments using a principal components analysis to derive scores for composite, motor, and cognitive progression. These scores were analyzed in linear regression in genome-wide association studies. We also performed a targeted analysis of the 90 PD risk loci from the latest case-control meta-analysis. RESULTS: There was no overlap between variants associated with PD risk, from case-control studies, and PD age at onset versus PD progression. The APOE ε4 tagging variant, rs429358, was significantly associated with composite and cognitive progression in PD. Conditional analysis revealed several independent signals in the APOE locus for cognitive progression. No single variants were associated with motor progression. However, in gene-based analysis, ATP8B2, a phospholipid transporter related to vesicle formation, was nominally associated with motor progression (P = 5.3 × 10-6 ). CONCLUSIONS: We provide early evidence that this new method in PD improves measurement of symptom progression. We show that the APOE ε4 allele drives progressive cognitive impairment in PD. Replication of this method and results in independent cohorts are needed. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC. on behalf of International Parkinson and Movement Disorder Society

Benefits, Barriers and Enablers of Breastfeeding: Factor Analysis of Population Perceptions in Western Australia

Objective: The objective of this study was to investigate knowledge and community perceptions of breastfeeding in Western Australia using a factor analysis approach. Methods: Data were pooled from five Nutrition Monitoring Survey Series which included information on breastfeeding from 4,802 Western Australian adults aged 18–64 years. Tetrachoric factor analysis was conducted for data reduction and significant associations identified using logistic, ordinal and poisson regression analyses. Results: Four factors were derived for benefits (it’s natural, good nutrition, good for the baby, and convenience), barriers (breastfeeding problems, poor community acceptability, having to go back to work, and inconvenience) and for enablers (breastfeeding education, community support, family support and not having to work).As assessed by standardized odds ratios the most important covariates across benefit factors were: importance of breastfeeding (ORs range from 1.22–1.44),female gender (ORs range from 0.80 to 1.46), being able to give a time for how long a baby should be breastfed (ORs range from 0.96 to 1.27) and education (less than high school to university completion) (ORs range from 0.95 to 1.23); the most important covariate across barrier factors was being able to give a time for how long a baby should be breastfed (ORs range from 0.89 to 1.93); and the most important covariates across all enabling factors were education (ORs range from 1.14 to1.32) and being able to give a time for how long a baby should be breastfed (ORs range from 1.17 to 1.42).Conclusions: Being female, rating breastfeeding as important, believing that babies should be breastfed for a period of time and education accounted for most of the statistically significant associations. The differences between male and female perceptions require investigation particularly in relation to returning to work

Potential climatic transitions with profound impact on Europe

We discuss potential transitions of six climatic subsystems with large-scale impact on Europe, sometimes denoted as tipping elements. These are the ice sheets on Greenland and West Antarctica, the Atlantic thermohaline circulation, Arctic sea ice, Alpine glaciers and northern hemisphere stratospheric ozone. Each system is represented by co-authors actively publishing in the corresponding field. For each subsystem we summarize the mechanism of a potential transition in a warmer climate along with its impact on Europe and assess the likelihood for such a transition based on published scientific literature. As a summary, the ‘tipping’ potential for each system is provided as a function of global mean temperature increase which required some subjective interpretation of scientific facts by the authors and should be considered as a snapshot of our current understanding. <br/

Abundance, movements and biodiversity of flying predatory insects in crop and non-crop agroecosystems

[EN] Predatory insects are key natural enemies that can highly reduce crops pest damage. However, there is a lack of knowledge about the movements of flying predatory insects in agroecosystems throughout the year. In particular, it is still unclear how these predators move from crop to non-crop habitats, which are the preferred habitats to overwinter and to spread during the spring and if these predators leave or stay after chemical treatments. Here, the Neuroptera, a generalist, highly mobile, flying predator order of insects, was selected as model. We studied the effects of farming management and the efficiency of edge shelterbelts, ground cover vegetation, and fruit trees canopy on holding flying predatory insects in Mediterranean traditional agroecosystems. Seasonal movements and winter effects were also assessed. We evaluated monthly nine fruit agroecosystems, six organic, and three pesticides sprayed, of 0.5-1 ha in eastern Spain during 3 years using two complementary methods, yellow sticky traps and aspirator. Results show surprisingly that the insect abundance was highest in pesticide sprayed systems, with 3.40 insects/sample versus 2.32 insects/sample in organic systems. The biodiversity indices were highest in agroecosystems conducted under organic management, with S of 4.68 and D of 2.34. Shelterbelts showed highest biodiversity indices, S of 3.27 and D of 1.93, among insect habitats. Insect species whose adults were active during the winter preferred fruit trees to spend all year round. However, numerous species moved from fruit trees to shelterbelts to overwinter and dispersed into the orchard during the following spring. The ground cover vegetation showed statistically much lower attractiveness for flying predatory insects than other habitats. 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Cytokine Levels Correlate with Immune Cell Infiltration after Anti-VEGF Therapy in Preclinical Mouse Models of Breast Cancer

The effect of blocking VEGF activity in solid tumors extends beyond inhibition of angiogenesis. However, no studies have compared the effectiveness of mechanistically different anti-VEGF inhibitors with respect to changes in tumor growth and alterations in the tumor microenvironment. In this study we use three distinct breast cancer models, a MDA-MB-231 xenograft model, a 4T1 syngenic model, and a transgenic model using MMTV-PyMT mice, to explore the effects of various anti-VEGF therapies on tumor vasculature, immune cell infiltration, and cytokine levels. Tumor vasculature and immune cell infiltration were evaluated using immunohistochemistry. Cytokine levels were evaluated using ELISA and electrochemiluminescence. We found that blocking the activation of VEGF receptor resulted in changes in intra-tumoral cytokine levels, specifically IL-1β, IL-6 and CXCL1. Modulation of the level these cytokines is important for controlling immune cell infiltration and ultimately tumor growth. Furthermore, we demonstrate that selective inhibition of VEGF binding to VEGFR2 with r84 is more effective at controlling tumor growth and inhibiting the infiltration of suppressive immune cells (MDSC, Treg, macrophages) while increasing the mature dendritic cell fraction than other anti-VEGF strategies. In addition, we found that changes in serum IL-1β and IL-6 levels correlated with response to therapy, identifying two possible biomarkers for assessing the effectiveness of anti-VEGF therapy in breast cancer patients