Diffractive imaging, in which image-forming optics are replaced by an inverse computation using scattered intensity data, could, in principle, realize wavelength-scale resolution in a transmission ...electron microscope. However, to date all implementations of this approach have suffered from various experimental restrictions. Here we demonstrate a form of diffractive imaging that unshackles the image formation process from the constraints of electron optics, improving resolution over that of the lens used by a factor of five and showing for the first time that it is possible to recover the complex exit wave (in modulus and phase) at atomic resolution, over an unlimited field of view, using low-energy (30 keV) electrons. Our method, called electron ptychography, has no fundamental experimental boundaries: further development of this proof-of-principle could revolutionize sub-atomic scale transmission imaging.
This document provides clinical recommendations for treatment of chronic obstructive pulmonary disease (COPD) exacerbations.Comprehensive evidence syntheses, including meta-analyses, were performed ...to summarise all available evidence relevant to the Task Force's questions. The evidence was appraised using the Grading of Recommendations, Assessment, Development and Evaluation approach and the results were summarised in evidence profiles. The evidence syntheses were discussed and recommendations formulated by a multidisciplinary Task Force of COPD experts.After considering the balance of desirable and undesirable consequences, quality of evidence, feasibility, and acceptability of various interventions, the Task Force made: 1) a strong recommendation for noninvasive mechanical ventilation of patients with acute or acute-on-chronic respiratory failure; 2) conditional recommendations for oral corticosteroids in outpatients, oral rather than intravenous corticosteroids in hospitalised patients, antibiotic therapy, home-based management, and the initiation of pulmonary rehabilitation within 3 weeks after hospital discharge; and 3) a conditional recommendation against the initiation of pulmonary rehabilitation during hospitalisation.The Task Force provided recommendations related to corticosteroid therapy, antibiotic therapy, noninvasive mechanical ventilation, home-based management, and early pulmonary rehabilitation in patients having a COPD exacerbation. These recommendations should be reconsidered as new evidence becomes available.
Outcomes after exacerbations of chronic obstructive pulmonary disease (COPD) requiring acute noninvasive ventilation (NIV) are poor and there are few treatments to prevent hospital readmission and ...death.
To investigate the effect of home NIV plus oxygen on time to readmission or death in patients with persistent hypercapnia after an acute COPD exacerbation.
A randomized clinical trial of patients with persistent hypercapnia (Paco2 >53 mm Hg) 2 weeks to 4 weeks after resolution of respiratory acidemia, who were recruited from 13 UK centers between 2010 and 2015. Exclusion criteria included obesity (body mass index BMI >35), obstructive sleep apnea syndrome, or other causes of respiratory failure. Of 2021 patients screened, 124 were eligible.
There were 59 patients randomized to home oxygen alone (median oxygen flow rate, 1.0 L/min interquartile range {IQR}, 0.5-2.0 L/min) and 57 patients to home oxygen plus home NIV (median oxygen flow rate, 1.0 L/min IQR, 0.5-1.5 L/min). The median home ventilator settings were an inspiratory positive airway pressure of 24 (IQR, 22-26) cm H2O, an expiratory positive airway pressure of 4 (IQR, 4-5) cm H2O, and a backup rate of 14 (IQR, 14-16) breaths/minute.
Time to readmission or death within 12 months adjusted for the number of previous COPD admissions, previous use of long-term oxygen, age, and BMI.
A total of 116 patients (mean SD age of 67 10 years, 53% female, mean BMI of 21.6 IQR, 18.2-26.1, mean SD forced expiratory volume in the first second of expiration of 0.6 L 0.2 L, and mean SD Paco2 while breathing room air of 59 7 mm Hg) were randomized. Sixty-four patients (28 in home oxygen alone and 36 in home oxygen plus home NIV) completed the 12-month study period. The median time to readmission or death was 4.3 months (IQR, 1.3-13.8 months) in the home oxygen plus home NIV group vs 1.4 months (IQR, 0.5-3.9 months) in the home oxygen alone group, adjusted hazard ratio of 0.49 (95% CI, 0.31-0.77; P = .002). The 12-month risk of readmission or death was 63.4% in the home oxygen plus home NIV group vs 80.4% in the home oxygen alone group, absolute risk reduction of 17.0% (95% CI, 0.1%-34.0%). At 12 months, 16 patients had died in the home oxygen plus home NIV group vs 19 in the home oxygen alone group.
Among patients with persistent hypercapnia following an acute exacerbation of COPD, adding home noninvasive ventilation to home oxygen therapy prolonged the time to readmission or death within 12 months.
clinicaltrials.gov Identifier: NCT00990132.
Readmission following COPD exacerbation is a common and challenging clinical problem. New approaches to predicting readmissions are required to help mitigate risk and develop novel interventions.
We ...conducted a prospective cohort study in 82 COPD patients admitted due to an exacerbation of COPD. Lung function measures spirometry, forced oscillation technique (FOT) indices and peak inspiratory flow rate (PIFR), inflammatory biomarkers and patient-reported outcomes including previous exacerbation history, breathlessness, quality of life and frailty were measured at admission and discharge. We prospectively followed patients for 30 and 90 days to identify predictors for readmission.
The readmission rate within 30 days was 38%, and 56% within 90 days. Previous exacerbations, higher COPD Assessment Test score at discharge, frailty, reduced PIFR and increased length of stay were significantly associated with 30-day readmission. PIFR at discharge and frailty had the highest predictive ability for 30-day readmission using area under receiver operating characteristic curves (AUC 0.86, 95% CI 0.78-0.95, p < 0.001 and AUC 0.81, 95% CI 0.71-0.90, p < 0.001, respectively). Ninety-day readmissions were significantly associated with previous exacerbations and hospitalisations, higher CAT score at discharge, frailty, depression, lower PIFR and greater expiratory flow limitation (EFL) in the supine position. The best predictive variable in multivariable analysis for both 30- and 90-day readmission was PIFR at discharge.
PIFR, CAT score, frailty, and EFL were found to be associated with 30- and 90-day readmission following COPD exacerbation. These findings help identify those at highest risk and to optimise care prior to discharge.
JARID2 (Jumonji, AT Rich Interactive Domain 2) pathogenic variants cause a neurodevelopmental syndrome, that is characterized by developmental delay, cognitive impairment, hypotonia, autistic ...features, behavior abnormalities and dysmorphic facial features. JARID2 encodes a transcriptional repressor protein that regulates the activity of various histone methyltransferase complexes. However, the molecular etiology is not fully understood, and JARID2-neurodevelopmental syndrome may vary in its typical clinical phenotype. In addition, the detection of variants of uncertain significance (VUSs) often results in a delay of final diagnosis which could hamper the appropriate care. In this study we aim to detect a specific and sensitive DNA methylation signature for JARID2-neurodevelopmental syndrome. Peripheral blood DNA methylation profiles from 56 control subjects, 8 patients with (likely) pathogenic JARID2 variants and 3 patients with JARID2 VUSs were analyzed. DNA methylation analysis indicated a clear and robust separation between patients with (likely) pathogenic variants and controls. A binary model capable of classifying patients with the JARID2-neurodevelopmental syndrome was constructed on the basis of the identified episignature. Patients carrying VUSs clustered with the control group. We identified a distinct DNA methylation signature associated with JARID2-neurodevelopmental syndrome, establishing its utility as a biomarker for this syndrome and expanding the EpiSign diagnostic test.
This document provides clinical recommendations for the prevention of chronic obstructive pulmonary disease (COPD) exacerbations. It represents a collaborative effort between the European Respiratory ...Society and the American Thoracic Society.Comprehensive evidence syntheses were performed to summarise all available evidence relevant to the Task Force's questions. The evidence was appraised using the Grading of Recommendations, Assessment, Development and Evaluation approach and the results were summarised in evidence profiles. The evidence syntheses were discussed and recommendations formulated by a multidisciplinary Task Force of COPD experts.After considering the balance of desirable (benefits) and undesirable consequences (burden in the form of adverse effects and cost), quality of evidence, feasibility, and acceptability of various interventions, the Task Force made recommendations for mucolytic, long-acting muscarinic antagonist, phosphodiesterase-4 inhibitor (roflumilast) and macrolide therapy, as well as a conditional recommendation against fluoroquinolone therapy. All of the recommendations were conditional, except for a strong recommendation for the use of a long-acting antimuscarinic agent
a long-acting β
-adrenergic, indicating that there was uncertainty about the balance of desirable and undesirable consequences of the intervention, and that well-informed patients may make different choices regarding whether to have or not have the specific intervention.The guideline summarises the evidence and provides recommendations for pharmacological therapy for the prevention of COPD exacerbations.
We report strongly nonreciprocal behavior for quantum dot exciton spins coupled to nanophotonic waveguides under resonant laser excitation. A clear dependence of the transmission spectrum on the ...propagation direction is found for a chirally coupled quantum dot, with spin up and spin down exciton spins coupling to the left and right propagation directions, respectively. The reflection signal shows an opposite trend to the transmission, which a numerical model indicates is due to direction-selective saturation of the quantum dot. The chiral spin-photon interface we demonstrate breaks reciprocity of the system and opens the way to spin-based quantum optical components such as optical diodes and circulators in a chip-based solid-state environment.
Advances in technology offer various solutions that might help optimize the care provided to patients living with chronic non-communicable diseases such as chronic obstructive pulmonary disease ...(COPD). However, the efficacy of tele-health in COPD is still controversial. Despite this, there appears to be widespread adoption of this technology.
To explore the international use of tele-heath for COPD, to assess the perceptions of clinicians employing tele-health in COPD, and to summarize the techniques that have been used by health care providers to personalize alarm limits for patients with COPD enrolled on tele-health programs.
A cross-sectional survey consisting of 15 questions was distributed and advertised to health care professionals worldwide. Questions were designed to cover five different aspects of tele-health in COPD: purpose of use, equipment type, clinician perceptions, variables monitored, and personalization of alarm limits.
A total of 138 participants completed the survey from 29 different countries. As high as 59% of the participants had ever used tele-health for COPD, and 33% still provided tele-health services to patients with COPD. Tele-health was most commonly used for baseline monitoring, with 90% believing it to be effective. The three most commonly monitored variables were oxygen saturation, heart rate, and the use of rescue medication.
Twenty-nine different countries use tele-health for managing COPD and therefore there is widespread international use of tele-health in COPD. The majority of providers thought tele-health was effective despite evidence to the contrary.
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