k-Nearest Neighbor Curves in Imaging Data Classification

Background: Lung disease quantification via medical image analysis is classically difficult. We propose a method based on normalized nearest neighborhood distance classifications for comparing individual CT scan air-trapping distributions (representing 3D segmented parenchyma). Previously, between-image comparisons were precluded by the variation inherent to parenchyma segmentations, the dimensions of which are patient- and image-specific by nature.Method: Nearest neighbor distance estimations are normalized by a theoretical distance according to the uniform distribution of air trapping. This normalization renders images (of different sizes, shapes, and/or densities) comparable. The estimated distances for the k-nearest neighbor describe the proximity of point patterns over the image. Our approach assumes and requires a defined homogeneous space; therefore, a completion pretreatment is applied beforehand.Results: Model robustness is characterized via simulation in order to verify that the required initial transformations do not bias uniformly sampled results. Additional simulations were performed to assess the discriminant power of the method for different point pattern profiles. Simulation results demonstrate that the method robustly recognizes pattern dissimilarity. Finally, the model is applied on real data for illustrative purposes.Conclusion: We demonstrate that a parenchyma-cuboid completion method provides the means of characterizing air-trapping patterns in a chosen segmentation and, importantly, comparing such patterns between patients and images

What is the remaining status of adaptive servo-ventilation? The results of a real-life multicenter study (OTRLASV-study). Adaptive servo-ventilation in real-life conditions

Backgrounds: As a consequence of the increased mortality observed in the SERVE-HF study, many questions concerning the safety and rational use of ASV in other indications emerged. The aim of this study was to describe the clinical characteristics of ASV-treated patients in real-life conditions. Methods: The OTRLASV-study is a prospective, 5-centre study including patients who underwent ASV-treatment for at least 1 year. Patients were consecutively included in the study during the annual visit imposed for ASV- reimbursement renewal. Results: 177/214 patients were analysed (87.57% male) with a median (IQ25–75) age of 71 (65–77) years, an ASV- treatment duration of 2.88 (1.76–4.96) years, an ASV-usage of 6.52 (5.13–7.65) hours/day, and 54.8% were previously treated via continuous positive airway pressure (CPAP). The median Epworth Scale Score decreased from 10 (6–13.5) to 6 (3–9) (p < 0.001) with ASV-therapy, the apnea-hypopnea-index decreased from 50 (38–62)/h to a residual device index of 1.9 (0.7–3.8)/h (p < 0.001). The majority of patients were classified in a Central-Sleep-Apnea group (CSA; 59.3%), whereas the remaining are divided into an Obstructive-Sleep-Apnea group (OSA; 20.3%) and a Treatment-Emergent-Central-Sleep-Apnea group (TECSA; 20.3%). The Left Ventricular Ejection Fraction (LVEF) was > 45% in 92.7% of patients. Associated comorbidities/etiologies were cardiac in nature for 75.7% of patients (neurological for 12.4%, renal for 4.5%, opioid-treatment for 3.4%). 9.6% had idiopathic central-sleep-apnea. 6.2% of the patients were hospitalized the year preceding the study for cardiological reasons. In the 6 months preceding inclusion, night monitoring (i.e. polygraphy or oximetry during ASV usage) was performed in 34.4% of patients, 25.9% of whom required a subsequent setting change. According to multivariable, logistic regression, the variables that were independently associated with poor adherence (ASV-usage ≤4 h in duration) were TECSA group versus CSA group (p = 0.010), a higher Epworth score (p = 0.019) and lack of a night monitoring in the last 6 months (p < 0.05). Conclusions: In real-life conditions, ASV-treatment is often associated with high cardiac comorbidities and high compliance. Future research should assess how regular night monitoring may optimize devices settings and patient management

Amyotrophic lateral sclerosis transcriptomics reveals immunological effects of low-dose interleukin-2

Amyotrophic lateral sclerosis is a fatal neurodegenerative disease causing upper and lower motor neuron loss and currently no effective disease-modifying treatment is available. A pathological feature of this disease is neuroinflammation, a mechanism which involves both CNS-resident and peripheral immune system cells. Regulatory T-cells are immune-suppressive agents known to be dramatically and progressively decreased in patients with amyotrophic lateral sclerosis. Low-dose interleukin-2 promotes regulatory T-cell expansion and was proposed as an immune-modulatory strategy for this disease. A randomized placebo-controlled pilot phase-II clinical trial called Immuno-Modulation in Amyotrophic Lateral Sclerosis was carried out to test safety and activity of low-dose interleukin-2 in 36 amyotrophic lateral sclerosis patients (NCT02059759). Participants were randomized to 1MIU, 2MIU-low-dose interleukin-2 or placebo and underwent one injection daily for 5 days every 28 days for three cycles. In this report, we describe the results of microarray gene expression profiling of trial participants' leukocyte population. We identified a dose-dependent increase in regulatory T-cell markers at the end of the treatment period. Longitudinal analysis revealed an alteration and inhibition of inflammatory pathways occurring promptly at the end of the first treatment cycle. These responses are less pronounced following the end of the third treatment cycle, although an activation of immune-regulatory pathways, involving regulatory T-cells and T helper 2 cells, was evident only after the last cycle. This indicates a cumulative effect of repeated low-dose interleukin-2 administration on regulatory T-cells. Our analysis suggested the existence of inter-individual variation amongst trial participants and we therefore classified patients into low, moderate and high-regulatory T-cell-responders. NanoString profiling revealed substantial baseline differences between participant immunological transcript expression profiles with the least responsive patients showing a more inflammatory-prone phenotype at the beginning of the trial. Finally, we identified two genes in which pre-treatment expression levels correlated with the magnitude of drug responsiveness. Therefore, we proposed a two-biomarker based regression model able to predict patient regulatory T-cell-response to low-dose interleukin-2. These findings and the application of this methodology could be particularly relevant for future precision medicine approaches to treat amyotrophic lateral sclerosis

Assessing the risks to Mediterranean islands ecosystems from non-native plant introductions.

Peer Reviewe

Why We Should Not Be Indifferent to Specification Choices for Difference‐in‐Differences

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/112198/1/hesr12270.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/112198/2/hesr12270-sup-0001-AuthorMatrix.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/112198/3/hesr12270-sup-0002-Appendix.pd

Habitat specificity of a threatened and endemic cliff-dwelling halophyte

Research ArticleCoastal areas and other saline environments are major contributors to regional and global biodiversity patterns. In these environments, rapidly changing gradients require highly specialized plants like halophytes. In European coastal cliff-tops, rocky and sandy seashores, and saltmarshes, typical halophytes from the genus Limonium are commonly found. Among them, the aneuploid tetraploid (2n ¼ 4x ¼ 35, 36, 37) Limonium multiflorum, endemic to the west coast of Portugal, is an interesting case study for investigating the ecology and conservation of a halophyte agamospermic species. Although it is listed in the IUCN red list of threatened species, information on its population size or rarity, as well as its ecology, in some respects is still unknown. Field surveys in the largest known population were performed (Raso cape, Portugal) in order to determine habitat requirements and conservation status. A total of 88 quadrats were monitored, 43 of which contained at least one L. multiflorum individual. For each sampled quadrat, four abiotic and four biotic variables as well as two spatially derived variables were recorded. Principal component analysis and cluster analysis showed narrow habitat specificity for this species which appeared to be intolerant to competition with invasive alien plants. We conclude that in situ conservation in a local ‘hotspot’ of this rare and vulnerable species emerges as a priority in order to ensure that biodiversity is not los

BMJ Open

Objectives Presently, those outcomes that should be prioritised for chronic obstructive pulmonary disease (COPD) exacerbation studies remain unclear. In order to coordinate multicentre studies on eosinophilia-driven corticosteroid therapy for patients hospitalised for acute exacerbation of COPD (AECOPD), we aimed to find consensus among experts in the domain regarding the prioritisation of outcomes. Design A modified Delphi study was proposed to recognised COPD experts. Two brainstorming questionnaires were used to collect potential outcomes. Four subsequent rounds of questionnaires were used to rank items according to a six-point Likert scale for their importance in the protocol, as well as for being the primary outcome. Priority outcome criteria were predefined as those for which ≥70% of experts indicated that the outcome was essential for interpreting study results. Setting COPD exacerbation management in France. Participants 34 experts recommended by the French Language Pulmonology Society were invited to participate. Of the latter, 21 experts participated in brainstorming, and 19 participated in all four ranking rounds. Results 105 outcomes were ranked. Two achieved consensus as candidate primary outcomes: (1) treatment failure defined as death from any cause or the need for intubation and mechanical ventilation, readmission because of COPD or intensification of pharmacologic therapy, and (2) the time required to meet predefined discharge criteria. The 10 secondary priority outcomes included survival, time with no sign of improvement, episodes of hospitalisation, exacerbation, pneumonia, mechanical or non-invasive ventilation and oxygen use, as well as comorbidities during the initial hospitalisation. Conclusions This Delphi consensus project generated and prioritised a great many outcomes, documenting current expert views concerning a diversity of COPD endpoints. Among the latter, 12 reached consensus as priority outcomes for evaluating the efficacy of eosinophil-driven corticosteroid therapy in AECOPD inpatients