Outcomes of Pulmonary Rehabilitation for COPD in Older Patients: A Comparative Study.

Pulmonary rehabilitation (PR) is established as an effective intervention in optimising function and quality of life in patients with chronic obstructive pulmonary disease (COPD). However, there are very limited data on the effectiveness of PR in older patients with COPD. We reviewed all patients attending an 8-week outpatient programme. Patients were divided into two groups; Group A (n = 202), below 70 years, and Group B (n = 122), above 70 years of age. Outcomes in both patient subgroups were compared using FEV1, Incremental Shuttle Walk Test (ISWT), Endurance Shuttle Walk Test (ESWT), Grip Strength, St. George's Respiratory Questionnaire (SGRQ), Hospital Anxiety and Depression Score (HADS), and COPD Assessment Test (CAT) score. Statistical analysis was conducted using Mann-Whitney non-parametric testing and chi-square testing for comparison of clinically relevant improvements between groups. There was no significant difference in PR outcomes between Group A and Group B using absolute values. Mean changes in ISWT for Groups A and B 39.7 m vs. 32.8 m (p = 0.63), respectively, SGRQ -2.5 vs. -2.8 (p = 0.95), HADS anxiety score -0.83 vs. -0.57 (p = 0.43) and HADS depression score -0.69 vs. -0.39 (p = 0.48), respectively. There was no difference in the proportion of patients who achieved the minimal clinically significant improvement in Group A versus Group B for parameters ISWT (38.6% vs 42.7%), SGRQ (27.8% vs 21.3%), and HADS total score (20.5% vs 28.1%). These data suggest that benefits of PR in COPD are not age dependent. Age should not be a barrier to enrolling patients with COPD in PR programmes.

End-to-end differentiable construction of molecular mechanics force fields.

Molecular mechanics (MM) potentials have long been a workhorse of computational chemistry. Leveraging accuracy and speed, these functional forms find use in a wide variety of applications in biomolecular modeling and drug discovery, from rapid virtual screening to detailed free energy calculations. Traditionally, MM potentials have relied on human-curated, inflexible, and poorly extensible discrete chemical perception rules (atom types) for applying parameters to small molecules or biopolymers, making it difficult to optimize both types and parameters to fit quantum chemical or physical property data. Here, we propose an alternative approach that uses graph neural networks to perceive chemical environments, producing continuous atom embeddings from which valence and nonbonded parameters can be predicted using invariance-preserving layers. Since all stages are built from smooth neural functions, the entire process-spanning chemical perception to parameter assignment-is modular and end-to-end differentiable with respect to model parameters, allowing new force fields to be easily constructed, extended, and applied to arbitrary molecules. We show that this approach is not only sufficiently expressive to reproduce legacy atom types, but that it can learn to accurately reproduce and extend existing molecular mechanics force fields. Trained with arbitrary loss functions, it can construct entirely new force fields self-consistently applicable to both biopolymers and small molecules directly from quantum chemical calculations, with superior fidelity than traditional atom or parameter typing schemes. When adapted to simultaneously fit partial charge models, espaloma delivers high-quality partial atomic charges orders of magnitude faster than current best-practices with low inaccuracy. When trained on the same quantum chemical small molecule dataset used to parameterize the Open Force Field ("Parsley") openff-1.2.0 small molecule force field augmented with a peptide dataset, the resulting espaloma model shows superior accuracy vis-á-vis experiments in computing relative alchemical free energy calculations for a popular benchmark. This approach is implemented in the free and open source package espaloma, available at https://github.com/choderalab/espaloma.

Characterization of Florida red tide aerosol and the temporal profile of aerosol concentration.

Red tide aerosols containing aerosolized brevetoxins are produced during the red tide bloom and transported by wind to coastal areas of Florida. This study reports the characterization of Florida red tide aerosols in human volunteer studies, in which an asthma cohort spent 1h on Siesta Beach (Sarasota, Florida) during aerosolized red tide events and non-exposure periods. Aerosol concentrations, brevetoxin levels, and particle size distribution were measured. Hourly filter samples were taken and analyzed for brevetoxin and NaCl concentrations. In addition, the aerosol mass concentration was monitored in real time. The results indicated that during a non-exposure period in October 2004, no brevetoxin was detected in the water, resulting in non-detectable levels of brevetoxin in the aerosol. In March 2005, the time-averaged concentrations of brevetoxins in water samples were moderate, in the range of 5-10 microg/L, and the corresponding brevetoxin level of Florida red tide aerosol ranged between 21 and 39 ng/m(3). The temporal profiles of red tide aerosol concentration in terms of mass, NaCl, and brevetoxin were in good agreement, indicating that NaCl and brevetoxins are components of the red tide aerosol. By continuously monitoring the marine aerosol and wind direction at Siesta Beach, we observed that the marine aerosol concentration varied as the wind direction changed. The temporal profile of the Florida red tide aerosol during a sampling period could be explained generally with the variation of wind direction.

Exposure and effect assessment of aerosolized red tide toxins (brevetoxins) and asthma.

BACKGROUND: In previous studies we demonstrated statistically significant changes in reported symptoms for lifeguards, general beach goers, and persons with asthma, as well as statistically significant changes in pulmonary function tests (PFTs) in asthmatics, after exposure to brevetoxins in Florida red tide (Karenia brevis bloom) aerosols. OBJECTIVES: In this study we explored the use of different methods of intensive ambient and personal air monitoring to characterize these exposures to predict self-reported health effects in our asthmatic study population. METHODS: We evaluated health effects in 87 subjects with asthma before and after 1 hr of exposure to Florida red tide aerosols and assessed for aerosolized brevetoxin exposure using personal and ambient samplers. RESULTS: After only 1 hr of exposure to Florida red tide aerosols containing brevetoxin concentrations > 57 ng/m(3), asthmatics had statistically significant increases in self-reported respiratory symptoms and total symptom scores. However, we did not see the expected corresponding changes in PFT results. Significant increases in self-reported symptoms were also observed for those not using asthma medication and those living >/= 1 mile from the coast. CONCLUSIONS: These results provide additional evidence of health effects in asthmatics from ambient exposure to aerosols containing very low concentrations of brevetoxins, possibly at the lower threshold for inducing a biologic response (i.e., toxicity). Consistent with the literature describing self-reported symptoms as an accurate measure of asthmatic distress, our results suggest that self-reported symptoms are a valuable measure of the extent of health effects from exposure to aerosolized brevetoxins in asthmatic populations.

Multi-Laboratory Study of Five Methods for the Determination of Brevetoxins in Shellfish Tissue Extracts.

A thirteen-laboratory comparative study tested the performance of four methods as alternatives to mouse bioassay for the determination of brevetoxins in shellfish. The methods were N2a neuroblastoma cell assay, two variations of the sodium channel receptor binding assay, competitive ELISA, and LC/MS. Three to five laboratories independently performed each method using centrally prepared spiked and naturally incurred test samples. Competitive ELISA and receptor binding (96-well format) compared most favorably with mouse bioassay. Between-laboratory relative standard deviations (RSDR) ranged from 10 to 20% for ELISA and 14 to 31% for receptor binding. Within-laboratory (RSDr) ranged from 6 to 15% for ELISA, and 5 to 31% for receptor binding. Cell assay was extremely sensitive but data variation rendered it unsuitable for statistical treatment. LC/MS performed as well as ELISA on spiked test samples but was inordinately affected by lack of toxin-metabolite standards, uniform instrumental parameters, or both, on incurred test samples. The ELISA and receptor binding assay are good alternatives to mouse bioassay for the determination of brevetoxins in shellfish.