A study to assess COPD Symptom-based Management and to Optimise treatment Strategy in Japan (COSMOS-J) based on GOLD 2011

Background and objective: The Global initiative for chronic Obstructive Lung Disease(GOLD) Committee has proposed a chronic obstructive pulmonary disease (COPD) assessment framework focused on symptoms and on exacerbation risk. This study will evaluate a symptom and exacerbation risk-based treatment strategy based on GOLD in a real-world setting in Japan. Optimal management of COPD will be determined by assessing symptoms using the COPD Assessment Test (CAT) and by assessing the frequency of exacerbations. Methods: This study (ClinicalTrials.gov identifier: NCT01762800) is a 24-week, multicenter, randomized, double-blind, double-dummy, parallel-group study. It aims to recruit 400 patients with moderate-to-severe COPD. Patients will be randomized to receive treatment with either salmeterol/fluticasone propionate (SFC) 50/250μg twice daily or with tiotropium bromide 18μg once daily. Optimal management of patients will be assessed at four-weekly intervals and, if patients remain symptomatic, as measured using the CAT, or experience an exacerbation, they have the option to step up to treatment with both drugs, ie, SFC twice daily and tiotropium once daily (TRIPLE therapy). The primary endpoint of the study will be the proportion of patients who are able to remain on the randomized therapy. Results: No data are available. This paper summarizes the methodology of the study in advance of the study starting. Conclusion: The results of this study will help physicians to understand whether TRIPLE therapy is more effective than either treatment strategy alone in controlling symptoms and exacerbations in patients with moderate-to-severe COPD. It will also help physicians to understand the GOLD recommendation work in Japan

New Universal Strain Software Accurately Assesses Cardiac Systolic and Diastolic Function Using Speckle Tracking Echocardiography

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108658/1/echo12512.pd

Random population fluctuations bias the Living Planet Index

The Living Planet Index (LPI) is a standardized indicator for tracking population trends through time. Due to its ability to aggregate many time series in a single metric, the LPI has been proposed as an indicator for the Convention on Biological Diversity’s post-2020 Global Biodiversity Strategy. However, here we show that random population fluctuations introduce biases when calculating the LPI. By combining simulated and empirical data, we show how random fluctuations lead to a declining LPI even when overall population trends are stable and imprecise estimates of the LPI when populations increase or decrease nonlinearly. We applied randomization null models that demonstrate how random fluctuations exaggerate declines in the global LPI by 9.6%. Our results confirm substantial declines in the LPI but highlight sources of uncertainty in quantitative estimates. Randomization null models are useful for presenting uncertainty around indicators of progress towards international biodiversity targets.DATA AVAILABILITY: Empirical data of population time series in the Living Planet database are available from the dedicated website maintained by the Zoological Society of London (ZSL) (http://stats.livingplanetindex.org/) and are subject to the Data Use Policy by the Indicators & Assessments Unit at the ZSL and WWF International. Simulated data to replicate the results are available from https://doi.org/10.5281/zenodo.4744533.CODE AVAILABILITY : All simulation outputs and code (R scripts) to reproduce the results in this manuscript are available from https://doi.org/10.5281/zenodo.4744533.EXTENDED DATA FIG. 1: The nine steps to calculating the Living Planet Index (LPI).EXTENDED DATA FIG. 2: The Living Planet Index (LPI) for randomly fluctuating populations that are stable on average.EXTENDED DATA FIG. 3: Starting population sizes of time series added to the Living Planet Index have declined between 1950 and 2015.EXTENDED DATA FIG. 4: Larger population fluctuations cause less precise estimates of the Living Planet Index (LPI) in nonlinear population trajectories.EXTENDED DATA FIG 5: Population fluctuations cause generalised additive models (GAM) to misestimate starting and ending populations when populations decrease from 100 to 40 individuals.EXTENDED DATA FIG 6: Population fluctuations cause generalised additive models (GAM) to misestimate starting and ending populations when populations increase from 100 to 160 individuals.EXTENDED DATA FIG 7: The reshuffling null model used to account for random population fluctuations.EXTENDED DATA FIG. 8: Cumulative population declines can occur in the Living Planet Index even when average population declines are zero.EXTENDED DATA FIG. 9: Cumulative population changes represent empirical trajectories more accurately than average changes as time series lengths increase.The National Research Foundation of South Africa and the Jennifer Ward Oppenheimer Research Grant.https://www.nature.com/natecolevolhj2022Zoology and Entomolog

Book reviews

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43350/1/11084_2005_Article_BF01808246.pd

A randomized trial of symptom-based management in Japanese patients with COPD.

Background: The Global initiative for chronic Obstructive Lung Disease strategy document for COPD recommends treatment changes according to the persistence of symptoms or exacerbations. This study assessed the feasibility and outcomes of a structured step-up/step-down treatment approach in a randomized controlled clinical trial setting. Methods: Japanese patients with moderate-to-severe COPD were randomized to blinded, double-dummy treatment with twice-daily fluticasone propionate/salmeterol (FP/SAL) 250/50 µg or once-daily tiotropium bromide (TIO) 18 µg for 24 weeks (dual bronchodilator was not available). At 4-weekly intervals, patients remaining symptomatic (COPD Assessment Test score >10) or experiencing an exacerbation were offered the option to use triple therapy. Primary endpoint was the proportion of patients remaining on randomized therapy. Results: In total, 406 patients participated (mean FEV1 59%±13% predicted; COPD Assessment Test 12±6). Of these, 204 and 201 patients were included in the FP/SAL and TIO groups, respectively, of whom 67% and 63% continued treatment throughout the study; this difference was not statistically significant. Time to first therapy switch was longer with FP/SAL, but not significantly (P=0.21). More patients in Global initiative for chronic Obstructive Lung Disease (2011 criteria) groups C/D switched (FP/SAL 55%, TIO 63%) than in groups A/B (FP/SAL 27%, TIO 27%). Conclusion: Given the choice, patients with more symptoms or those experiencing an exacerbation will agree to step-up therapy. Effectiveness of disease management pathways can be tested using double-blind studies

High-Resolution Patterned Cellular Constructs by Droplet-Based 3D Printing

AbstractBioprinting is an emerging technique for the fabrication of living tissues that allows cells to be arranged in predetermined three-dimensional (3D) architectures. However, to date, there are limited examples of bioprinted constructs containing multiple cell types patterned at high-resolution. Here we present a low-cost process that employs 3D printing of aqueous droplets containing mammalian cells to produce robust, patterned constructs in oil, which were reproducibly transferred to culture medium. Human embryonic kidney (HEK) cells and ovine mesenchymal stem cells (oMSCs) were printed at tissue-relevant densities (107 cells mL−1) and a high droplet resolution of 1 nL. High-resolution 3D geometries were printed with features of ≤200 μm; these included an arborised cell junction, a diagonal-plane junction and an osteochondral interface. The printed cells showed high viability (90% on average) and HEK cells within the printed structures were shown to proliferate under culture conditions. Significantly, a five-week tissue engineering study demonstrated that printed oMSCs could be differentiated down the chondrogenic lineage to generate cartilage-like structures containing type II collagen.</jats:p

Linking rattiness, geography and environmental degradation to spillover Leptospira infections in marginalised urban settings: An eco-epidemiological community-based cohort study in Brazil

Background: Zoonotic spillover from animal reservoirs is responsible for a significant global public health burden, but the processes that promote spillover events are poorly understood in complex urban settings. Endemic transmission of Leptospira, the agent of leptospirosis, in marginalised urban communities occurs through human exposure to an environment contaminated by bacteria shed in the urine of the rat reservoir. However, it is unclear to what extent transmission is driven by variation in the distribution of rats or by the dispersal of bacteria in rainwater runoff and overflow from open sewer systems. Methods: We conducted an eco-epidemiological study in a high-risk community in Salvador, Brazil, by prospectively following a cohort of 1401 residents to ascertain serological evidence for leptospiral infections. A concurrent rat ecology study was used to collect information on the fine-scale spatial distribution of 'rattiness', our proxy for rat abundance and exposure of interest. We developed and applied a novel geostatistical framework for joint spatial modelling of multiple indices of disease reservoir abundance and human infection risk. Results: The estimated infection rate was 51.4 (95%CI 40.4, 64.2) infections per 1000 follow-up events. Infection risk increased with age until 30 years of age and was associated with male gender. Rattiness was positively associated with infection risk for residents across the entire study area, but this effect was stronger in higher elevation areas (OR 3.27 95% CI 1.68, 19.07) than in lower elevation areas (OR 1.14 95% CI 1.05, 1.53). Conclusions: These findings suggest that, while frequent flooding events may disperse bacteria in regions of low elevation, environmental risk in higher elevation areas is more localised and directly driven by the distribution of local rat populations. The modelling framework developed may have broad applications in delineating complex animal-environment-human interactions during zoonotic spillover and identifying opportunities for public health intervention

Energy transport in the thermosphere during the solar storms of April 2002

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94816/1/jgra17969.pd

Diurnal variations of temperature and winds inferred from TIMED and UARS measurements

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95001/1/jgra18181.pd

Pharmacological Blockade of Serotonin 5-HT7 Receptor Reverses Working Memory Deficits in Rats by Normalizing Cortical Glutamate Neurotransmission

The role of 5-HT7 receptor has been demonstrated in various animal models of mood disorders; however its function in cognition remains largely speculative. This study evaluates the effects of SB-269970, a selective 5-HT7 antagonist, in a translational model of working memory deficit and investigates whether it modulates cortical glutamate and/or dopamine neurotransmission in rats. The effect of SB-269970 was evaluated in the delayed non-matching to position task alone or in combination with MK-801, a non-competitive NMDA receptor antagonist, and, in separate experiments, with scopolamine, a non-selective muscarinic antagonist. SB-269970 (10 mg/kg) significantly reversed the deficits induced by MK-801 (0.1 mg/kg) but augmented the deficit induced by scopolamine (0.06 mg/kg). The ability of SB-269970 to modulate MK-801-induced glutamate and dopamine extracellular levels was separately evaluated using biosensor technology and microdialysis in the prefrontal cortex of freely moving rats. SB-269970 normalized MK-801 -induced glutamate but not dopamine extracellular levels in the prefrontal cortex. Rat plasma and brain concentrations of MK-801 were not affected by co-administration of SB-269970, arguing for a pharmacodynamic rather than a pharmacokinetic mechanism. These results indicate that 5-HT7 receptor antagonists might reverse cognitive deficits associated with NMDA receptor hypofunction by selectively normalizing glutamatergic neurotransmission