Symptom relief is a key treatment goal in patients with chronic obstructive pulmonary disease (COPD). However, there are limited data available on the response to bronchodilator therapy in patients at low risk of exacerbations with different levels of symptom severity. This study compared treatment responses in patients with a range of symptom severities as indicated by baseline COPD assessment test (CAT) scores.
 
  The 24-week EMAX trial evaluated the benefits of umeclidinium/vilanterol 
  umeclidinium or salmeterol in symptomatic patients at low exacerbation risk who were not receiving inhaled corticosteroids. This analysis assessed lung function, symptoms, health status, and short-term deterioration outcomes in subgroups defined by a baseline CAT score [<20 (
  ) and ⩾20 (pre-specified)]. Outcomes were also assessed using 
  fractional polynomial modelling with continuous transformations of baseline CAT score covariates.
 
  Of the intent-to-treat population (
   = 2425), 56% and 44% had baseline CAT scoreerities, not only those with severe symptoms (CAT ⩾20).
  NCT03034915, 2016-002513-22 (EudraCT number).
  
 Patients with symptomatic COPD benefit similarly from dual bronchodilator treatment with umeclidinium/vilanterol. Fractional polynomial analyses demonstrated the greatest treatment differences favouring dual therapy in patients with a CAT score less then 20, although benefits were seen up to scores of 30. This suggests that dual bronchodilation may be considered as initial therapy for patients across a broad range of symptom severities, not only those with severe symptoms (CAT ⩾20).Trial registration NCT03034915, 2016-002513-22 (EudraCT number).The reviews of this paper are available via the supplemental material section.
  Susceptibility to VT/VF (ventricular tachycardia/fibrillation) is difficult to predict in patients with ischemic cardiomyopathy either by clinical tools or by attempting to translate cellular mechanisms to the bedside.
 
  To develop computational phenotypes of patients with ischemic cardiomyopathy, by training then interpreting machine learning of ventricular monophasic action potentials (MAPs) to reveal phenotypes that predict long-term outcomes.
 
  We recorded 5706 ventricular MAPs in 42 patients with coronary artery disease and left ventricular ejection fraction ≤40% during steady-state pacing.  https://www.selleckchem.com/products/Eloxatin.html  Patients were randomly allocated to independent training and testing cohorts in a 7030 ratio, repeated K=10-fold. Support vector machines and convolutional neural networks were trained to 2 end points (1) sustained VT/VF or (2) mortality at 3 years. Support vector machines provided superior classification. For patient-level predictions, we computed personalized MAP scores as the proportion of MAP beats predicting each end point. Patient-level predictions in independent test cohorts yielded c-statistics of 0.90 for sustained VT/VF (95% CI, 0.76-1.00) and 0.91 for mortality (95% CI, 0.83-1.00) and were the most significant multivariate predictors. Interpreting trained support vector machine revealed MAP morphologies that, using in silico modeling, revealed higher L-type calcium current or sodium-calcium exchanger as predominant phenotypes for VT/VF.
 
  Machine learning of action potential recordings in patients revealed novel phenotypes for long-term outcomes in ischemic cardiomyopathy. Such computational phenotypes provide an approach which may reveal cellular mechanisms for clinical outcomes and could be applied to other conditions.
 Machine learning of action potential recordings in patients revealed novel phenotypes for long-term outcomes in ischemic cardiomyopathy. Such computational phenotypes provide an approach which may reveal cellular mechanisms for clinical outcomes and could be applied to other conditions.The goal of this study was to develop methods for the evaluation of green fluorescent protein (GFP) and GFP transcript biodistribution in paraformaldehyde-fixed paraffin-embedded (PFPE) eye sections to assess the effectiveness of Adeno-associated virus (AAV) gene delivery in an experimental ocular toxicity study. Female C57BL/6NTac mice were administered AAV2-enhancedGFP vector once via subretinal injection. One group also received anti-inflammatory therapy (meloxicam). Immunohistochemistry (IHC) and RNA in situ hybridization (ISH) for GFP were performed on PFPE serial eye sections and evaluated using semiquantitative methods. On day 43, GFP labeling in both IHC and ISH sections was greatest in the retinal pigment epithelium, compared with other retinal layers in which expression was negative to moderate. Despite the presence of IHC GFP labeling in the photoreceptor layer (PRL) in some animals, only low numbers of transduced cells were detected by ISH in the PRL. Simultaneous analysis of IHC and ISH may be needed for comprehensive assessment of gene transduction and protein biodistribution. This study demonstrates approaches for semiquantitative evaluation of IHC and ISH that allow interpretation and reporting of GFP expression in toxicity studies.Previous findings suggest a right hemispheric contribution to body image distortions only in women. Here we set out to replicate this finding and investigate whether the sex of the body image would play a role in this lateralization. We report here two experiments of body size estimation using the divided visual field methodology. In Experiment 1 we found no effect of visual field, participant sex, and body image sex. We discuss the results in terms of the androgynous-like stimuli appearance. In Experiment 2 we increased the dimorphism of body image stimuli. Surprisingly, we observed a different pattern. Both men and women overestimated the size of female models presented in both visual fields, but the size of male models was underestimated for presentations in the left visual field compared to presentations in the right visual field. We found no differences between men and women. Our results suggest that the differences in lateralization of body image distortions between men and women observed in previous studies can be attributed to the sex of the body image. To the best of our knowledge, this is the first study to show that the sex of the body image modulates lateralization and body image distortion.