Chronic Obstructive Pulmonary Disease: Lobar Analysis with Hyperpolarized 129Xe MR Imaging.

Purpose To compare lobar ventilation and apparent diffusion coefficient (ADC) values obtained with hyperpolarized xenon 129 ((129)Xe) magnetic resonance (MR) imaging to quantitative computed tomography (CT) metrics on a lobar basis and pulmonary function test (PFT) results on a whole-lung basis in patients with chronic obstructive pulmonary disease (COPD). Materials and Methods The study was approved by the National Research Ethics Service Committee; written informed consent was obtained from all patients. Twenty-two patients with COPD (Global Initiative for Chronic Obstructive Lung Disease stage II-IV) underwent hyperpolarized (129)Xe MR imaging at 1.5 T, quantitative CT, and PFTs. Whole-lung and lobar (129)Xe MR imaging parameters were obtained by using automated segmentation of multisection hyperpolarized (129)Xe MR ventilation images and hyperpolarized (129)Xe MR diffusion-weighted images after coregistration to CT scans. Whole-lung and lobar quantitative CT-derived metrics for emphysema and bronchial wall thickness were calculated. Pearson correlation coefficients were used to evaluate the relationship between imaging measures and PFT results. Results Percentage ventilated volume and average ADC at lobar (129)Xe MR imaging showed correlation with percentage emphysema at lobar quantitative CT (r = -0.32, P < .001 and r = 0.75, P < .0001, respectively). The average ADC at whole-lung (129)Xe MR imaging showed moderate correlation with PFT results (percentage predicted transfer factor of the lung for carbon monoxide [Tlco]: r = -0.61, P < .005) and percentage predicted functional residual capacity (r = 0.47, P < .05). Whole-lung quantitative CT percentage emphysema also showed statistically significant correlation with percentage predicted Tlco (r = -0.65, P < .005). Conclusion Lobar ventilation and ADC values obtained from hyperpolarized (129)Xe MR imaging demonstrated correlation with quantitative CT percentage emphysema on a lobar basis and with PFT results on a whole-lung basis. (©) RSNA, 2016

The giant planet orbiting the cataclysmic binary DP Leonis

Planets orbiting post-common envelope binaries provide fundamental information on planet formation and evolution, especially for the yet nearly unexplored class of circumbinary planets. We searched for such planets in \odp, an eclipsing short-period binary, which shows long-term eclipse-time variations. Using published, reanalysed, and new mid-eclipse times of the white dwarf in DP\,Leo, obtained between 1979 and 2010, we find agreement with the light-travel-time effect produced by a third body in an elliptical orbit. In particular, the measured binary period in 2009/2010 and the implied radial velocity coincide with the values predicted for the motion of the binary and the third body around the common center of mass. The orbital period, semi-major axis, and eccentricity of the third body are P_c = 28.0 +/- 2.0 yrs, a_c = 8.2 +/- 0.4 AU, and e_c = 0.39 +/- 0.13. Its mass of M_c sin(i_c) = 6.1 +/- 0.5 M_J qualifies it as a giant planet. It formed either as a first generation object in a protoplanetary disk around the original binary or as a second generation object in a disk formed in the common envelope shed by the progenitor of the white dwarf. Even a third generation origin in matter lost from the present accreting binary can not be entirely excluded. We searched for, but found no evidence for a fourth body.Comment: Accepted by A&

Effect of Home Noninvasive Ventilation With Oxygen Therapy vs Oxygen Therapy Alone on Hospital Readmission or Death After an Acute COPD Exacerbation

Importance: 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. Objective: 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. Design, Setting, and Participants: 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. Interventions: 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. Main Outcomes and Measures: 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. Results: 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. Conclusions and Relevance: 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. Trial Registration: clinicaltrials.gov Identifier: NCT00990132

Polar Invasion and Translocation of Neisseria meningitidis and Streptococcus suis in a Novel Human Model of the Blood-Cerebrospinal Fluid Barrier

Acute bacterial meningitis is a life-threatening disease in humans. Discussed as entry sites for pathogens into the brain are the blood-brain and the blood-cerebrospinal fluid barrier (BCSFB). Although human brain microvascular endothelial cells (HBMEC) constitute a well established human in vitro model for the blood-brain barrier, until now no reliable human system presenting the BCSFB has been developed. Here, we describe for the first time a functional human BCSFB model based on human choroid plexus papilloma cells (HIBCPP), which display typical hallmarks of a BCSFB as the expression of junctional proteins and formation of tight junctions, a high electrical resistance and minimal levels of macromolecular flux when grown on transwell filters. Importantly, when challenged with the zoonotic pathogen Streptococcus suis or the human pathogenic bacterium Neisseria meningitidis the HIBCPP show polar bacterial invasion only from the physiologically relevant basolateral side. Meningococcal invasion is attenuated by the presence of a capsule and translocated N. meningitidis form microcolonies on the apical side of HIBCPP opposite of sites of entry. As a functionally relevant human model of the BCSFB the HIBCPP offer a wide range of options for analysis of disease-related mechanisms at the choroid plexus epithelium, especially involving human pathogens

Protection of athymic (Nu/Nu) BALB/c mice against Plasmodium berghei by splenocytes from normal (Nu/ +) BALB/c mice

Athymic BALB/c (Nu/Nu) mice died at 7-13 days after inoculation (DAI) of Plasmodium berghei NK65, whereas their heterozygous (Nu/+) littermates died at 7-8 DAI. Nude (Nu/Nu) mice, reconstituted with 2 x 10(7) splenocytes from uninfected heterozygous (Nu/+) littermates at 20 days before parasite inoculation (DBI), died about 2 days earlier than control nude mice; nude mice reconstituted at 10 or 2 DBI lived 2 to 4 days longer than control nudes; and nude mice reconstituted 2 DAI lived even longer and some survived. These findings indicate that P. berghei NK65 induces at least two T-cell dependent immune phenomena, one suppressive and the other stimulatory. Reconstitution of nude mice with T-cells from BALB/c (Nu/+) mice appeared to reduce or bypass suppressive T-cell activities which allowed the formation of a protective immune response by some of the nude mice

ANIMAL MODELS FOR THE STUDY OF LEISHMANIASIS IMMUNOLOGY

Leishmaniasis remains a major public health problem worldwide and is classified as Category I by the TDR/WHO, mainly due to the absence of control. Many experimental models like rodents, dogs and monkeys have been developed, each with specific features, in order to characterize the immune response to Leishmania species, but none reproduces the pathology observed in human disease. Conflicting data may arise in part because different parasite strains or species are being examined, different tissue targets (mice footpad, ear, or base of tail) are being infected, and different numbers (“low” 1×102 and “high” 1×106) of metacyclic promastigotes have been inoculated. Recently, new approaches have been proposed to provide more meaningful data regarding the host response and pathogenesis that parallels human disease. The use of sand fly saliva and low numbers of parasites in experimental infections has led to mimic natural transmission and find new molecules and immune mechanisms which should be considered when designing vaccines and control strategies. Moreover, the use of wild rodents as experimental models has been proposed as a good alternative for studying the host-pathogen relationships and for testing candidate vaccines. To date, using natural reservoirs to study Leishmania infection has been challenging because immunologic reagents for use in wild rodents are lacking. This review discusses the principal immunological findings against Leishmania infection in different animal models highlighting the importance of using experimental conditions similar to natural transmission and reservoir species as experimental models to study the immunopathology of the disease

Data-driven approach to understanding exciton-exciton interactions in CsPbBr₃ nanocrystals

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemical Engineering, 2019Cataloged from PDF version of thesis.Includes bibliographical references (pages 105-109).Lead halide perovskites are a rapidly developing class of materials of interest for optoelectronic applications. They have a number of desirable properties such as long carrier diffusion lengths and defect tolerance that arise from the materials' unique dielectric properties. Although much of the initial interest in lead halide perovskites was geared towards producing highly efficient solar cells from the bulk material, cubic perovskite nanocrystals are a strong candidate system for light-emitting applications. Optical gain in semiconductor nanocrystals relies on emission from biexciton or doubly excited states. Knowledge of the spectral properties of biexciton states is critical for understanding optical gain development as well as many-body interactions between charge carriers more broadly. In this thesis, we develop and demonstrate a data-driven approach to characterizing the energetics and dynamics of biexciton states in CsPbBr₃ nanocrystals using TA spectroscopy.We then use the understanding developed using the TA data to guide experiments using other techniques and further examine the physical phenomena that influence these excited states. In Chapter 2, we describe our data-driven method in detail and demonstrate its effectiveness in extracting spectral information about CsPbBr₃ nanocrystals. The method combines the target analysis fit commonly employed in organic systems with Bayesian inference and a Markov chain Monte Carlo sampler to accurately characterize the model uncertainty and vet the model itself. In Chapter 3, we apply the analysis developed in Chapter 2 to a size-series of CsPbBr₃ nanocrystals to extract the biexciton and exciton component TA spectra as a function of nanocrystal size. We find that the exciton and biexciton spectra have distinctive shapes, in contrast with the common assumption about these spectra.The biexciton spectra a broader and slightly blue-shifted from the exciton spectrum, and the broadening and blue-shifting both increase as the nanocrystal size decreases. We verify this with our own time-resolved photoluminescence experiments. In Chapter 4, we propose and discuss in detail the development of an experiment to verify our hypothesis for why the exciton-exciton interaction is repulsive - the effect of polaron formation. We describe the development of a femtosecond stimulated Raman spectroscopy experiment to directly observe polaron formation and the challenges of performing this technique at high repetition rate. The central goal of this thesis is to describe a more careful approach to analyzing spectroscopic data.by Matthew N. Ashner.Ph. D.Ph.D. Massachusetts Institute of Technology, Department of Chemical Engineerin

High repetition-rate femtosecond stimulated Raman spectroscopy with fast acquisition

Time-resolved femtosecond stimulated Raman spectroscopy (FSRS) is a powerful tool for investigating ultrafast structural and vibrational dynamics in light absorbing systems. However, the technique generally requires exposing a sample to high laser pulse fluences and long acquisition times to achieve adequate signal-to-noise ratios. Here, we describe a time-resolved FSRS instrument built around a Yb ultrafast amplifier operating at 200 kHz, and address some of the unique challenges that arise at high repetition-rates. The setup includes detection with a 9 kHz CMOS camera and an improved dual-chopping scheme to reject scattering artifacts that occur in the 3-pulse configuration. The instrument demonstrates good signal-to-noise performance while simultaneously achieving a 3-6 fold reduction in pulse energy and a 5-10 fold reduction in acquisition time relative to comparable 1 kHz instruments. ©2018 Optical Society of America.NSF - Division of Chemistry and Division of Materials Research (Award no. 1452857